490 Matching Annotations
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  2. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Von Hippel-Lindau disease in a Newfoundland kindred.
    3
    1. ClingenBaseline 31 Oct 2026
      recognized in a large family that originated in Newfoundland but has some members who live in New Brunswick and Ontario. A collaborative investigation was begun in 1982 to document the number of affected members and the extent of their disease and to improve management of the disease. The condition has been documented in 38 members of the family, 28 living and 10 dead. The most common manifestations are retinal angioma (present in 60% of the gene carriers) and pheochromocytoma (present in 53%). Of the 28 living affected members 14 had been identified before the study began. Only 3 of the 14 patients in whom the disease was subsequently diagnosed presented with symptoms; in the remaining 11 the condition was detected by routine screening. Overall the mean age at the time of diagnosis was 23 years; in the 21 affected members of the fourth generation it was 18 years.

      PatientID: I-2

      KindredID: 1

      Case: M, Age Unknown (deceased), Ethnicity Unknown

      DiseaseAssertion: Assumed VHL

      FamilyInfo: 38 family members had been affected at the date of 1986, and 10 had passed away. Pheochromocytoma, cerebellar, spinal and retinal hemangioblastomas, and various cysts were clinical manifestations of VHL seen throughout the family. This male (I-2) appears to be the furthest traced relative with the presumed mutation, passing on to 3 of his 4 offspring, and dozens of kin thereafter. See Fig 1 for family pedigree.

      CasePresentingHPOs: N/A

      CaseHPOFreeText: Affected, although details are unknown.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: Although never given at the time of this publication, the germline mutation is confirmed in this family in later publications (PMID 7987306; 29437867) for this specific family. It can only be assumed this member had the VHL mutation.

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline RefSeq:N/A CivicName:R167W(c.499C>T) ProteinPosition:167 MutationType:missense_variant;transition AminoAcidChange:ARGtoTRP cDNAposition:499 Familial FamilyPedigree ClinVarID:2218 ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 30 Oct 2026
      recognized in a large family that originated in Newfoundland but has some members who live in New Brunswick and Ontario. A collaborative investigation was begun in 1982 to document the number of affected members and the extent of their disease and to improve management of the disease. The condition has been documented in 38 members of the family, 28 living and 10 dead. The most common manifestations are retinal angioma (present in 60% of the gene carriers) and pheochromocytoma (present in 53%). Of the 28 living affected members 14 had been identified before the study began. Only 3 of the 14 patients in whom the disease was subsequently diagnosed presented with symptoms; in the remaining 11 the condition was detected by routine screening. Overall the mean age at the time of diagnosis was 23 years; in the 21 affected members of the fourth generation it was 18 years.

      PatientID: IV-23

      KindredID: 1

      Case: F, Age Unknown, Ethnicity Unknown

      DiseaseAssertion: Assumed VHL

      FamilyInfo: 38 family members had been affected at the date of 1986, and 10 had passed away. Pheochromocytoma, cerebellar, spinal and retinal hemangioblastomas, and various cysts were clinical manifestations of VHL seen throughout the family. This patient (IV-23) appears to have inherited this disease from her father. See Fig. 1 for family pedigree.

      CasePresentingHPOs: HP:0009711 (retinal capillary hemangioma)

      CaseHPOFreeText: This member had retinal angiomas which were not further described.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: Although never given at the time of this publication, the germline mutation is confirmed in this family in later publications (PMID 7987306; 29437867) for this specific family. It is only here assumed this member had the VHL mutation.

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline RefSeq:N/A DiseaseEntity:retinalcapillaryhemangioma cDNAposition:499 CivicName:R167W(c.499C>T) ProteinPosition:167 MutationType:missense_variant;transition AminoAcidChange:ARGtoTRP ClinVarID:2218 ClinVarID:Yes Familial FamilyPedigree inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    3. ClingenBaseline 30 Oct 2026
      recognized in a large family that originated in Newfoundland but has some members who live in New Brunswick and Ontario. A collaborative investigation was begun in 1982 to document the number of affected members and the extent of their disease and to improve management of the disease. The condition has been documented in 38 members of the family, 28 living and 10 dead. The most common manifestations are retinal angioma (present in 60% of the gene carriers) and pheochromocytoma (present in 53%). Of the 28 living affected members 14 had been identified before the study began. Only 3 of the 14 patients in whom the disease was subsequently diagnosed presented with symptoms; in the remaining 11 the condition was detected by routine screening. Overall the mean age at the time of diagnosis was 23 years; in the 21 affected members of the fourth generation it was 18 years.

      PatientID: IV-38

      KindredID: 1

      Case: M, Age Unknown, Ethnicity Unknown

      DiseaseAssertion: Assumed VHL

      FamilyInfo: 38 family members had been affected at the date of 1986, and 10 had passed away. Pheochromocytoma, cerebellar, spinal and retinal hemangioblastomas, and various cysts were clinical manifestations of VHL seen throughout the family. This patient (IV-38) appears to have inherited this disease from his mother, along with many of his siblings. See Fig. 1 for family pedigree.

      CasePresentingHPOs: HP:0002666 (pheochromocytoma)

      CaseHPOFreeText: This member was examined in St. Johns at the Memorial University of Newfoundland. He had pheochromocytoma which was not further described.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: Although never given at the time of this publication, the germline mutation is confirmed in this family in later publications (PMID 7987306; 29437867) for this specific family. It is only here assumed this member had the VHL mutation.

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline RefSeq:N/A DiseaseEntity:pheochromocytoma ClinVarID:2218 ClinVarID:Yes Familial FamilyPedigree CivicName:R167W(c.499C>T) cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP MutationType:missense_variant;transition inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC1490656/
  3. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Genotype-Phenotype Correlation in Patients With Germline Mutations of VHL, RET, SDHB, and SDHD Genes: Thai Experience
    1
    1. ClingenBaseline 31 Oct 2026
      p.Arg161X41F+CHB, RCC, pancreatic cyst

      PatientID: 4

      KindredID: 4

      Case: F, 41Y0M, Ethnicity unknown

      DiseaseAssertion: VHL

      FamilyInfo: Familial VHL mutation - This one index case and their 4 relatives harbored p.Arg161X mutation - all with the same phenotypes hemangioblastoma, renal cell carcinoma and pancreatic cysts

      CasePresentingHPOs: HP:0010797; HP:0005584; HP:0001737 (hemangioblastoma; renal cell carcinoma; pancreatic cysts)

      CaseHPOFreeText: With an age of diagnosis of VHL at 41

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: Patients with clinical manifestations suggestive of VHL or MEN2 were first screened for VHL or RET mutation, respectively. Possible screening of RET, SDHB and SDHD as well

      PreviouslyPublished: N/A

      SupplementalData: Yes

      Variant: p.R161* (c.481C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 2217 https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: R161* (c.481C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:hemangioblastoma DiseaseEntity:renalcellcarcinoma DiseaseEntity:pancreaticcysts Mutation:Germline CivicName:R161*(c.481C>T) cDNAposition:481 ProteinPosition:161 AminoAcidChange:ARGtoTER MutationType:stop_gained ClinVarID:2217 ClinVarID:Yes Familial PreviousTesting:RET/SDHB/SDHD AssumedRefSeq:NM_000551.3 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC5404897/
  4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Molecular diagnosis of von Hippel-Lindau disease in a kindred with a predominance of familial phaeochromocytoma
    1
    1. ClingenBaseline 31 Oct 2026
      Patients: Two generations of a family consisting of 15 individuals were studied.

      PatientID: II:3

      KindredID: 1

      Case: F, 48Y0M, Spanish

      DiseaseAssertion: assumed VHL

      FamilyInfo: Spanish family of 15 members studied, over 2 generations. 6 members had VHL presentations, 1 was a carrier, and 4 others had the mutation, while 2 were not sequenced. This patient’s 2 children presented with the VHL mutation, and her brother and 3 of his children presented with VHL symptoms

      CasePresentingHPOs: HP:0002666; HP:0009711 (pheochromocytoma, retinal capillary hemangiomas)

      CaseHPOFreeText: First studied at 43Y, this patient had a right accumulation of pheos at 6cm, and retinal angiomas

      CaseNotHPOs: HP:0006880 (cerebellar hemangioblastoma)

      CaseNotHPOFreeText: Brain MRI and CT-scans were normal.

      CasePreviousTesting: RET

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: p.R238T, C>T

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Spanish DiseaseEntity:pheochromocytoma DiseaseEntity:retinalcapillaryhemangioma AgeOfPresentation:pheochromocytoma:43 AgeOfPresentation:retinalcapillaryhemangioma:43 Mutation:Germline AssumedRefSeq:AF010238.1 Familial FamilyPedigree PreviousTesting:RET ClinVarID:Yes ClinVarID:2218 MutationType:missense_variant;transition CivicName:R167W(c.499C>T) cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/9156047/
  5. www.nature.com www.nature.com
    A family with hydrocephalus as a complication of cerebellar hemangioblastoma: identification of Pro157Leu mutation in the VHL gene
    1
    1. ClingenBaseline 31 Oct 2026
      We report on a Japanese VHL family in which two of the three affected members developed acute occlusive hydrocephalus that necessitated emergency surgery for ventricular shunt or drainage.

      PatientID: 3

      KindredID: 1

      Case: F, 14Y0M, Japanese

      DiseaseAssertion: assumed VHL

      FamilyInfo: Mother (39Y) with retinal angiomas and cerebellar hemangioblastoma, and her older sister (P1) with cerebellar hemangioblastoma, retinal capillary hemangioma, pancreatic cysts and a hearing impairment both had the p.P86L VHL mutation. Father did not.

      CasePresentingHPOs: HP:0006880; HP:0010302; HP:0009711; HP:0001737; HP:0000107 (cerebellar hemangioblastoma; spinal cord tumor; retinal capillary hemangioma; Pancreatic cysts; renal cyst)

      CaseHPOFreeText: at age 14 had 3 small inter cranial tumors (not removed) and by at 19 years had obstructive hydrocephalus caused by enlargement of the cerebellar tumors (hemangioblastomas). Retinal angiomas were found in the right eye, cystic lesions in the pancreas and the left kidney, and a cystic tumor in the cervical cord

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.P86L (c.257C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 182977 https://www.ncbi.nlm.nih.gov/clinvar/variation/182977/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: P86L (c.257C>T)

      MultipleGeneVariants: N/A

      ClinVarID:182977 ClinVarID:Yes Mutation:Germline AssumedRefSeq:NM_000551.3 InheritancePattern:AutosomalDominant Familial FamilyPedigree CivicName:P86L(c.257C>T) cDNAposition:257 ProteinPosition:86 AminoAcidChange:PROtoLEU MutationType:missense_variant;transition Ethnicity:Japanese DiseaseEntity:cerebellarhemangioblastoma DiseaseEntity:spinalcordtumor DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:pancreaticcysts DiseaseEntity:renalcyst AgeOfPresentation:cerebellarhemangioblastoma:14 DiseaseEntity:VHL inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    nature.com/articles/jhg20009
  6. www-sciencedirect-com.uhn.idm.oclc.org www-sciencedirect-com.uhn.idm.oclc.org
    Denaturing High Performance Liquid Chromatography Detection of SDHB, SDHD, and VHL Germline Mutations in Pheochromocytoma
    1
    1. ClingenBaseline 31 Oct 2026
      c.250G > T(p.Val84Leu)

      PatientID: None

      KindredID: 2

      Case: age, sex, ethnicity unknown

      DiseaseAssertion: pheochromocytoma

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0002666 (pheochromocytoma)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.V84L (c.250G>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2236 https://www.ncbi.nlm.nih.gov/clinvar/variation/2236/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence:N/A

      MutationType: missense_variant; transversion

      CivicName: V84L (c.250G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:pheochromocytoma Mutation:Germline RefSeq:NM_000551.3 CivicName:V84L(c.250G>T) AminoAcidChange:VALtoLEU ProteinPosition:84 cDNAposition:250 MutationType:missense_variant;transversion ClinVarID:2236 ClinVarID:Yes NoFamilyInfo inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    www-sciencedirect-com.uhn.idm.oclc.org/science/article/pii/S0022480408005271
  7. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Outcome and genetic analysis of patients affected by retinal capillary hemangioblastoma in von Hippel Lindau syndrome
    1
    1. ClingenBaseline 30 Oct 2026
      Patient P8 In October 2019, visual impairment was diagnosed in a 14-year-old boy. BCVA was 20/20 and 20/640 in OD and OS, respectively. Four peripheral RCHs were detected in OD. In OS, multiple RCHs were present; the largest was located temporally, and it consisted in the coalescence of many RCHs. The visual impairment of OS was due to the severe exudative process which involved the macula. Moreover, FA revealed numerous microhemangioblastomas that could not be detected using other diagnostic techniques. Laser therapy was performed in OU, but vitreous hemorrhage occurred in OS. Therefore, three anti-VEGF IV (bevacizumab) and simultaneous transscleral cryotherapies were performed under general anesthesia. Many laser sessions were necessary to obtain regression of the RCHs. Further investigations revealed the presence of a cerebellar hemangioblastoma.

      PatientID: 8

      KindredID: 4

      Case: M, 14Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: A family pedigree is provided in figure 1. The parents of patient 8 were molecularly tested and neither possessed the mutation; thus, the mutation was identified as de novo. Neither parent had VHL syndrome characterized by retinal capillary hemangiomas (RCHs).

      CasePresentingHPOs: HP:0006880; HP:0009711 (Cerebellar hemangioblastoma; Retinal capillary hemangioma)

      CaseHPOFreeText: In 2019, a 14-year-old boy was diagnosed with visual impairment, due to visual acuity of 20/20 in the right eye and 20/640 in the left eye. Four peripheral RCHs were detected in the right eye. The visual impairment of the left eye was due to the severe exudative process involving the macula. Moreover, numerous microhemangioblastomas were revealed by fluorescein angiography. Laser therapy was performed in both eyes, but vitreous hemorrhage occurred in the left eye. Bevacizumab was given three times, as well simultaneous cryotherapies were performed under general anesthesia. Many laser sessions were performed for regression of the RCHs to occur. Further testing revealed a cerebellar hemangioblastoma.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: Patient did not have other known tumours.

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R113* (c.337C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 220414, https://www.ncbi.nlm.nih.gov/clinvar/variation/220414/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: R113* (c.337C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant MutationType:stop_gained Mutation:Germline FamilyPedigree ClinVarID:Yes ClinVarID:220414 CivicName:R113*(c.337C>T) cDNAPosition:337 ProteinPosition:113 AminoAcidChange:ARGtoTER DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:cerebellarhemangioblastoma AgeOfPresentation:retinalcapillaryhemangioma:14 AgeOfPresentation:cerebellarhemangioblastoma:14 InheritancePattern:DeNovoAssertion AssumedRefSeq:NM_000551.3 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC8416136/
  8. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Somatic inactivation of the VHL gene in Von Hippel-Lindau disease tumors.
    1
    1. ClingenBaseline 30 Oct 2026

      PatientID: 1

      KindredID: 38

      Case: Sex, Age, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0005584 (renal cell carcinoma)

      CaseHPOFreeText: one RCC tumor was detected in this patient

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.Q73* (c.217C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: p.Q73* (c.430C>T)

      ClinVarID: 223164 https://www.ncbi.nlm.nih.gov/clinvar/variation/223164/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: Tested the RCC tumor for somatic mutations but did not detect any

      MutationType: stop_gained

      CivicName: Q73* (c.217C>T)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:renalcellcarcinoma CivicName:Q73*(c.217C>T) cDNAposition:217 ProteinPosition:73 AminoAcidChange:GLNtoTER MutationType:stop_gained ClinVarID:223164 ClinVarID:Yes InheritancePattern:AutosomalDominant NoFamilyInfo RefSeq:AF010238.1 Mutation:Germline inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC1712486/
  9. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Genotype-phenotype correlations in Chinese von Hippel–Lindau disease patients
    1
    1. ClingenBaseline 30 Oct 2026

      PatientID: 94

      KindredID: 31

      Case: F, 56Y0M, Chinese

      DiseaseAssertion: VHL

      FamilyInfo: The proband (patient 31) has a son who has also genetically confirmed with the mutation. The proband's son presented at age 29 with retinal angioma, renal cell carcinoma, multiple pancreatic cysts/tumors, and pheochromocytoma.

      CasePresentingHPOs: HP:0010797; HP:0005584; HP:0001737; HP:0001732 (Hemangioblastoma, Renal cell carcinoma, Pancreatic cysts, Abnormality of the pancreas)

      CaseHPOFreeText: The proband presented with renal cell carcinoma and multiple pancreatic cysts/tumors at 51, and CNS hemangioblastoma at age 56.

      CaseNotHPOs: HP:0002666; HP:0009711 (Pheochromocytoma, Retinal capillary hemangioma)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: This patient was also published in a later paper by Wang et al., 2018 (PMID: 29330336).

      SupplementalData: Patient and family genotype-phenotype information is listed in Supplementary Table 1.

      Variant: p.E94* (c.280G>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 584477; https://www.ncbi.nlm.nih.gov/clinvar/variation/584477/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: E94* (c.280G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Chinese Mutation:Germline AssumedRefSeq:NM_000551.3 DiseaseEntity:VHL DiseaseEntity:hemangioblastoma DiseaseEntity:renalcellcarcinoma DiseaseEntity:pancreaticcysts DiseaseEntity:abnormalityofthepancreas AgeOfPresentation:hemangioblastoma:56 AgeOfPresentation:renalcellcarcinoma:53 AgeOfPresentation:pancreaticcysts:53 AgeOfPresentation:abnormalityofthepancreas:53 CivicName:E94*(c.280G>T) cDNAposition:280 ProteinPosition:94 AminoAcidChange:GLUtoTER ClinVarID:584477 ClinVarID:Yes MutationType:missense_variant;transversion SupplementalData Familial inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC5503545/
  10. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Molecular Characterization of a Novel Germline VHL Mutation by Extensive In Silico Analysis in an Indian Family with Von Hippel-Lindau Disease
    1
    1. ClingenBaseline 30 Oct 2026
      another affected relative [III-A, in the pedigree]

      PatientID: III-A

      KindredID: 1

      Case: M, 30Y0M, EthnicityUnknown

      DiseaseAssertion: VHL

      FamilyInfo: Multiple first- and second-degree relatives affected with similar phenotypes. Of these, he is genetically tested and found to share VHL mutations with his uncle (proband).

      CasePresentingHPOs: N/A

      CaseHPOFreeText: Paper asserts that this individual presented with VHL phenotypes but does not specify which.

      CaseNotHPOs: NA

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: Information obtained from Figure 1

      Variant: p.L158Q (c.473T>A)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 376048, https://www.ncbi.nlm.nih.gov/clinvar/variation/376048/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transversion

      CivicName: P86S (c.256C>T) and Splice Region (c.340+5G>C)

      MultipleGeneVariants: Germline, VHL, c.340+5G>C

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL Mutation:Germline RefSeq:NM_000551 AssumedRefSeq:NM_000551.3 cDNAposition:473 ProteinPosition:158 AminoAcidChange:LEUtoGLN ClinVarID:376048 ClinVarID:Yes MultipleVHLVariants MutationType:missense_variant;transversion PreviousTesting: N/A FamilyPedigree Familial SupplementalData CivicName:P86S(c.256C>T)andSpliceRegion(c.340+5G>C) inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC4812357/
  11. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Clinical presentation, genotype-phenotype correlations, and outcome of pancreatic neuroendocrine tumors in Von Hippel-Lindau syndrome
    1
    1. ClingenBaseline 30 Oct 2026
      9PExon 3Nonsensec.481C>Tp. Arg161TerPan/Kid-Cysts, RCC

      PatientID: 9

      KindredID: 7

      Case: Sex Unknown, Age Unknown, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0005584; HP:0001737; HP:0000107 (Renal cell carcinoma; pancreatic cyst; renal cyst)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: MEN1/ RET

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R161* (c.481C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2217 https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: R161* (c.481C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline RefSeq:NM_000551 PreviousTesting:RET DiseaseEntity:renalcellcarcinoma DiseaseEntity:pancreaticcysts DiseaseEntity:renalcyst DiseaseEntity:VHL ProteinPosition:161 cDNAposition:481 CivicName:R161*(c.481C>T) MutationType:stop_gained AminoAcidChange:ARGtoTER ClinVarID:2217 ClinVarID:Yes NoFamilyInfo inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC8440302/
  12. onlinelibrary.wiley.com onlinelibrary.wiley.com
    Germline mutations in the von Hippel–Lindau disease tumor suppressor gene: Correlations with phenotype
    1
    1. ClingenBaseline 30 Oct 2026

      GroupID: 2612

      DiseaseAssertion: assumed VHL

      GroupSize: 7

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: N/A

      GroupAgeRange: N/A

      GroupInfo: Familial VHL stated; 7 family members recorded with this mutation.

      GroupPresentingHPOs: HP:0010797; HP:0005584; HP:0009711 (hemangioblastoma, renal cell carcinoma, retinal capillary hemangioma)

      GroupHPOFreeText: 5 members had an angioma (retinal hemangioma), 2 had RCC, and all 7 members had CNS hemangioblastoma

      GroupNotHPOs: HP:0002666 (pheochromocytoma)

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: 19464396

      SupplementalData: N/A

      Variant: p.P86L (c.257C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: p.P86L (c.470C>T)

      ClinVarID: 182977 https://www.ncbi.nlm.nih.gov/clinvar/variation/182977/

      CAID: CA020186 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.257C%3ET

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transition

      CivicName: P86L (c.257C>T)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:hemangioblastoma Mutation:Germline CivicName:P86L(c.257C>T) cDNAposition:257 ProteinPosition:86 AminoAcidChange:PROtoLEU CAID:CA020186 ClinVarID:182977 Familial MutationType:missense_variant;transition RefSeq:AF010238.1 InheritancePattern:AutosomalDominant ClinVarID:Yes DiseaseEntity:retinalcapillaryhemangioma FamilyCohort inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    onlinelibrary.wiley.com/doi/10.1002/humu.1380050109
  13. www.karger.com www.karger.com
    Germline Mutation in the von Hippel-Lindau Gene in Kuwait
    2
    1. ClingenBaseline 30 Oct 2026

      PatientID: III-19

      KindredID: 1

      Case: F, Age Unknown, Middle Eastern

      DiseaseAssertion: VHL

      FamilyInfo: Multigenerational Kuwaiti family with Arabian and Persian genetic admixture. Thirteen members of the family had been clinically diagnosed as having VHL. Patient 1-I had 6 children, 5 of which were found with VHL and the p.W117C mutation. 7/20 of her grandchildren also found to have VHL and the same mutation.

      CasePresentingHPOs: HP:0010797; HP:0006770 (hemangioblastoma; clear cell renal cell carcinoma)

      CaseHPOFreeText: Member had clear cell renal carcinomas in addition to hemangioblastomas

      CaseNotHPOs: HP:0002666 (pheochromocytoma)

      CaseNotHPOFreeText: Lacked evidence of any pheos.

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.W117C (c.351G>T)

      LegacyVariant: p.Trp117Cys (c.564G>T)

      CaseProblemVariantFreeText: N/A

      ClinVarID: 167827 https://www.ncbi.nlm.nih.gov/clinvar/variation/167827/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: W117C (c.351G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:MiddleEastern DiseaseEntity:VHL DiseaseEntity:clearcellrenalcellcarcinoma DiseaseEntity:hemangioblastoma Mutation:Germline RefSeq:AF010238.1 CivicName:W117C(c.351G>T) cDNAposition:351 ProteinPosition:117 AminoAcidChange:TRPtoCYS MutationType:missense_variant;transversion ClinVarID:167827 ClinVarID:Yes Familial FamilyPedigree ExperimentalAssay inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 30 Oct 2026

      PatientID: III-18

      KindredID: 1

      Case: F, Age Unknown, Middle Eastern

      DiseaseAssertion: VHL

      FamilyInfo: Multigenerational Kuwaiti family with Arabian and Persian genetic admixture. Thirteen members of the family had been clinically diagnosed as having VHL. Patient 1-I had 6 children, 5 of which were found with VHL and the p.W117C mutation. 7/20 of her grandchildren also found to have VHL and the same mutation.

      CasePresentingHPOs: HP:0010797; HP:0006770 (hemangioblastoma; clear cell renal cell carcinoma)

      CaseHPOFreeText: Member had clear cell renal carcinomas in addition to hemangioblastomas

      CaseNotHPOs: HP:0002666 (pheochromocytoma)

      CaseNotHPOFreeText: Lacked evidence of any pheos.

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.W117C (c.351G>T)

      LegacyVariant: p.Trp117Cys (c.564G>T)

      CaseProblemVariantFreeText: N/A

      ClinVarID: 167827 https://www.ncbi.nlm.nih.gov/clinvar/variation/167827/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: W117C (c.351G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:MiddleEastern DiseaseEntity:VHL DiseaseEntity:clearcellrenalcellcarcinoma DiseaseEntity:hemangioblastoma Mutation:Germline RefSeq:AF010238.1 CivicName:W117C(c.351G>T) cDNAposition:351 AminoAcidChange:TRPtoCYS MutationType:missense_variant;transversion ClinVarID:167827 ClinVarID:Yes Familial FamilyPedigree ExperimentalAssay inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    karger.com/Article/Abstract/141504
  14. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Improved detection of germline mutations in the von Hippel-Lindau disease tumor suppressor gene
    1
    1. ClingenBaseline 30 Oct 2026

      GroupID: 202

      DiseaseAssertion: VHL

      GroupSize: N/A

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: N/A

      GroupAgeRange: N/A

      GroupInfo: VHL family found to have the c.712C>T (R167W) germline variant of the VHL gene. The number of family members included in this study is not specified.

      GroupPresentingHPOs: HP:0002666 (Pheochromocytoma)

      GroupHPOFreeText: Number of family affected members is not specified.

      GroupNotHPOs: N/A

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: c.712C>T

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:pheochromocytoma Mutation:Germline RefSeq:AF010238.1 cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP ClinVarID:2218 ClinVarID:Yes MutationType:missense_variant;transition CivicName:R167W(c.499C>T) Familial FamilyCohort inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/9829911/
  15. onlinelibrary-wiley-com.myaccess.library.utoronto.ca onlinelibrary-wiley-com.myaccess.library.utoronto.ca
    The von Hippel–Lindau (VHL) germline mutation V84L manifests as early‐onset bilateral pheochromocytoma
    1
    1. ClingenBaseline 30 Oct 2026
      The propositus underwent bilateral adrenalectomy for bilateral pheochromocytoma at age 23 years. Thereafter she remained well until age 54 years when a small vascular lesion, possibly a spinal hemangioblastoma, was identified by a screening MRI. No other central nervous system abnormalities were detected and her ophthalmologic examination was normal. An abdominal ultrasound scan demonstrated a 2.8-cm cyst in the left kidney. A year later she complained of right leg weakness, and slight weakness was confirmed by physical examination. A repeat MRI scan of the spine demonstrated a tiny, avidly enhancing nodule on the dorsal surface of the spinal cord at C3 with a diffuse area of high signal within the cord at that level, similar in appearance to one year prior

      PatientID: None

      KindredID: Family C

      Case: M, 54Y0M, Ethnicity Unknown

      DiseaseAssertion: Assumed VHL

      FamilyInfo: There was no family history of VHL disease or familial pheochromocytoma. Her parents (mother age 85, father age 79) were asymptomatic and were not available for DNA testing. A 58-year-old maternal half-brother was tested and did not carry the mutation.

      CasePresentingHPOs: HP:0006748, HP:0000107, HP:0009713 (adrenal pheochromocytoma, renal cyst, spinal hemangioblastoma)

      CaseHPOFreeText: The patient had bilateral pheochromocytoma. A small vascular lesion was identified by a screening MRI, which that authors of the papers assumed could possibly a spinal hemangioblastoma,

      CaseNotHPOs: None

      CaseNotHPOFreeText: No other central nervous system abnormalities were detected and her ophthalmologic examination was normal.

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.V84L (c.250G>T)

      LegacyVariant: p.V84L (c.463G>T)

      ClinVar: 2236 https://www.ncbi.nlm.nih.gov/clinvar/variation/2236/

      CAID: CA020170 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.250G%3ET

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: V84L (c.250G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:spinalhemangioblastoma DiseaseEntity:adrenalpheochromocytoma DiseaseEntity:renalcyst AgeOfpresentation:adrenalpheochromocytoma:23 AgeOfpresentation:spinalhemangioblastoma:54 AgeOfpresentation:renalcyst:54 Mutation:Germline cDNAposition:250 ProteinPosition:84 AminoAcidChange:VALtoLEU ClinVarID:2236 MutationType:missense_variant;transversion CivicName:V84L(c.463G>T) FamilyPedigree AssumedRefSeq:NM_000551.3 ClinVarID:Yes NonFamilial inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    onlinelibrary-wiley-com.myaccess.library.utoronto.ca/doi/full/10.1002/ajmg.a.31116
  16. www.sciencedirect.com www.sciencedirect.com
    Identification of a new VHL exon and complex splicing alterations in familial erythrocytosis or von Hippel-Lindau disease
    1
    1. ClingenBaseline 30 Oct 2026
      F6

      PatientID: None (Father)

      KindredID: F6

      Case: M, Age Unknown, Ethnicity Unknown

      DiseaseAssertion: Asymptomatic

      FamilyInfo: N/A

      CasePresentingHPOs: N/A

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.Q164H (c.492G>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 456566, https://www.ncbi.nlm.nih.gov/clinvar/variation/456566/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: Q164H (c.492G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:Asymptomatic Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:492 ProteinPosition:164 AminoAcidChange:GLNtoHIS ClinVarID:456566 ClinVarID:Yes MutationType:missense_variant;transversion CivicName:Q164H(c.492G>T) FamilyPedigree inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    sciencedirect.com/science/article/pii/S0006497120320206
  17. jnccn.org jnccn.org
    Exceptional Response to Temsirolimus in a Metastatic Clear Cell Renal Cell Carcinoma With an Early Novel MTOR-Activating Mutation
    1
    1. ClingenBaseline 30 Oct 2026
      Case ReportA 57-year-old Caucasian woman with an unremarkable past medical history presented with lumbar pain. Physical examination revealed a mass on the right flank. An FDG-PET scan revealed a renal mass highly suggestive of malignancy, signs of liver spread, and pelvic and lumbar spinal cord bone metastases (Figure 1A). Tumor staging at initial diagnosis was pT1bN0M1 (stage IV). In April 2007, an open right radical nephrectomy was performed. The histopathologic report revealed Fuhrman grade 4 advanced ccRCC. According to the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic model,14 the patient was classified as being in the intermediate-risk group based on 2 risk factors for the prognostic score: Karnofsky performance status of 70% and a serum lactic dehydrogenase level >1.5 times the upper limit of normal. She received palliative radiotherapy View Full Size Figure 1.(A) Initial tumor dissemination detected by PET/CT (arrows). (B) MRI showing skull metastasis (arrow), which was surgically removed in 2015.Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 15, 11; 10.6004/jnccn.2017.7018Download FigureDownload figure as PowerPoint slideFigure 1.(A) Initial tumor dissemination detected by PET/CT (arrows). (B) MRI showing skull metastasis (arrow), which was surgically removed in 2015.Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 15, 11; 10.6004/jnccn.2017.7018Download FigureDownload figure as PowerPoint slide for a painful right iliac metastasis and started sunitinib treatment at 50 mg/d on a 4 weeks on, 2 weeks off schedule (4/2). After 2 cycles, all tumoral lesions had progressed and treatment was switched to sorafenib, 400 mg twice daily. New response assessment after 2 cycles revealed disease progression with new liver and bone lesions and clinical deterioration. In March 2008, the patient started temsirolimus at 25 mg weekly and experienced a remarkable clinical benefit. She had a partial response according to RECIST criteria, with a time to best response after starting temsirolimus of 6 weeks (temsirolimus start: March 3, 2008; response at first reevaluation: April 16, 2008), and experienced overall good tolerance; she continued temsirolimus for >7 years. Main toxicity consisted of 3 different pneumonitis episodes (grade 1–3) that required dose interruptions or reductions. In August 2015, a new solitary bone metastasis arose in the skull, whereas others remained with no change (Figure 1B). A complete resection of the lesion was performed followed by local radiotherapy. At 21 months after the metastasectomy, the patient continues on treatment with biweekly temsirolimus in combination with denosumab, with no tumor progression.We performed WES in 3 different regions of the primary tumor obtained before treatment, in the skull metastasis resected 7 years after temsirolimus treatment initiation, and in the germline DNA obtained from the patient's blood. The mean depth of coverage was >80x for the 3 regions of the primary tumors, 136x for the metastasis, and 94x for the blood (see supplemental eAppendix 1 for details regarding methodology, available online with this article at JNCCN.org). The number of tumor mutations (single nucleotide variants and indels) leading to nonsynonymous coding or loss-of-function (LOF) variants in the primary tumor was 160. Tumor mutations refer to those detected in the tumor but absent in the blood. In total, 116, 76, and 65 mutations were detected in each of the 3 tumor regions and from these, 41 were shared (Figure 2; supplemental eTable 1). Among the shared tumor mutations, 39 were missense variants and 2 were LOF variants caused by frameshifts. The variants affecting genes frequently mutated in ccRCC were detected in all tumor samples analyzed: VHL (c.263G>T; p.W88L), BAP1 (c.1359dup; p.E454Rfs*15), and MTOR (c.5920T>C; p.Y1974H), and were validated by Sanger sequencing. In ccRCC the primary driver event is VHL inactivation, and thus VHL mutations are early alterations present in all tumor cells.15 The MTOR mutation frequencies detected in the different tumor samples sequenced were similar to those found for VHL, indicating that the MTOR mutation was also a truncal event in this patient (average ratio of 1.1; supplemental eTable 1). View Full Size Figure 2.Mutations revealed by whole-exome sequencing (WES). (A) Venn diagram indicating the number of tumor (absent in blood) loss-of-function and nonsynonymous coding variants identified through WES in 3 regions (R1–R3) of the primary tumor. Shared variants affecting relevant clear cell renal cell carcinoma genes are indicated below the arrow. (B) Representative genome images from the Integrative Genomics Viewer (Broad Institute), along with the number of reads for the reference (ref) and variant allele of the MTOR Y1974H mutation, and Sanger sequencing chromatogram.Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 15, 11; 10.6004/jnccn.2017.7018Download FigureDownload figure as PowerPoint slideFigure 2.Mutations revealed by whole-exome sequencing (WES). (A) Venn diagram indicating the number of tumor (absent in blood) loss-of-function and nonsynonymous coding variants identified through WES in 3 regions (R1–R3) of the primary tumor. Shared variants affecting relevant clear cell renal cell carcinoma genes are indicated below the arrow. (B) Representative genome images from the Integrative Genomics Viewer (Broad Institute), along with the number of reads for the reference (ref) and variant allele of the MTOR Y1974H mutation, and Sanger sequencing chromatogram.Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 15, 11; 10.6004/jnccn.2017.7018Download FigureDownload figure as PowerPoint slide View Full Size Figure 3.Functional assessment of MTOR p.Y1974H variant. Constructs expressing wild-type (WT) mTOR, mTOR Y1974H, and mTOR S2215Y (a positive control for mTOR activation) were transfected in HEK293 cells and the effect of phosphorylation of the downstream target S6K1 (pS6K1) was tested with Western blot. (A) Western blot analysis 24 hours after transfection cells were serum-starved for 24 hours (Starving) and then stimulated with 1% or 10% fetal bovine serum for 2 hours (Stimulation). In the Starving assay, lanes 1–2, 3–4, and 5–6 are duplicates from different experiments. (B) Cells transfected with mTOR constructs were treated with 2.5, 12.5, and 100 nM of rapamycin (rap) for 6 hours.Abbreviation: GAPDH, glyceraldehyde 3-phosphate dehydrogenase.Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 15, 11; 10.6004/jnccn.2017.7018Download FigureDownload figure as PowerPoint slideFigure 3.Functional assessment of MTOR p.Y1974H variant. Constructs expressing wild-type (WT) mTOR, mTOR Y1974H, and mTOR S2215Y (a positive control for mTOR activation) were transfected in HEK293 cells and the effect of phosphorylation of the downstream target S6K1 (pS6K1) was tested with Western blot. (A) Western blot analysis 24 hours after transfection cells were serum-starved for 24 hours (Starving) and then stimulated with 1% or 10% fetal bovine serum for 2 hours (Stimulation). In the Starving assay, lanes 1–2, 3–4, and 5–6 are duplicates from different experiments. (B) Cells transfected with mTOR constructs were treated with 2.5, 12.5, and 100 nM of rapamycin (rap) for 6 hours.Abbreviation: GAPDH, glyceraldehyde 3-phosphate dehydrogenase.Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 15, 11; 10.6004/jnccn.2017.7018Download FigureDownload figure as PowerPoint slide For BAP1 mutation, the average ratio was 0.66. Other genes implicated in cancer with mutations included BCL11B, CIC, EML4, KMT2C, NOTCH1, and RANBP2 (see supplemental eTable 1).To assess the effect of the MTOR novel variant p.Y1974H, HEK293 cells were transfected with constructs expressing the wild-type mTOR protein or the Y1974H variant protein. The mTOR-activating mutation S2215Y was used as control for the experiments. The Thr389 phospho-S6K1 (pS6K1) levels, which represent TORC1 activity, were augmented for the Y1974H variant compared with mTOR wild-type, and similar to those obtained for S2215Y (Figure 3A), indicating that mTOR Y1974H activates mTORC1. In addition, we observed that mTOR Y1974H was sensitive to rapamycin (Figure 3B). mTOR Y1974H also led to an increased number of cells in S phase with a concomitant decrease in G0/G1, and an alteration in forward scatter (data related to an alteration in cell size) compared with mTOR wild-type and similar to mTOR S2215Y (supplemental eFigure 1).16 Immunohistologic analysis of the tumor samples revealed activation of the mTOR pathway through a positive immunostaining of phospho-S6, a downstream target of mTOR (Figure 4A–C), with the metastasis staining being more intense than that in the primary tumor. The staining of p-ERK (Figure4 D–F) was weak in the primary tumor, whereas the metastasis exhibited a nuclear and cytoplasmatic intense and extensive staining.WES of the metastasis that arose 7 years after starting temsirolimus treatment revealed 80 tumor nonsynonymous coding or LOF variants (71 missense, 2 in-frame deletions, and 7 LOF) present in the tumor and absent in the blood. Of these, 51 were shared with the primary tumor and 29 were exclusively present in the metastasis (supplemental eTable 1). Among the genes exclusively mutated in the metastasis, only 3 (CRTC3, KAT6B, PBRM1) were in the Cancer Gene Census (CGC) but none were directly related to the MTOR pathway, and the variants have not been previously described in tumors, according to the COSMIC database.The full region of the MTOR FKBP-rapamycin binding domain (FRB), including intronic regions, was sequenced by Sanger. However, no metastasis-specific variants were detected.

      PatientID: None

      KindredID: 1

      Case: F, 39Y0M, Ethnicity Unknown

      DiseaseAssertion: Clear cell renal cell carcinoma

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0006770 (Clear cell renal cell carcinoma)

      CaseHPOFreeText: A 57-year-old Caucasian woman with an unremarkable past medical history presented with lumbar pain. Physical examination revealed a mass on the right flank. An FDG-PET scan revealed a renal mass highly suggestive of malignancy, signs of liver spread, and pelvic and lumbar spinal cord bone metastases. Open right radical nephrectomy was performed. The histopathologic report revealed Fuhrman grade 4 advanced ccRCC. New response assessment after 2 cycles of treatment revealed disease progression with new liver and bone lesions and clinical deterioration. In August 2015, a new solitary bone metastasis arose in the skull, whereas others remained with no change.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: Supplementary eTable1

      Variant: p.W88L (c.263G>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: N/A

      CAID: CA351750675, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA351750675

      gnomAD: N/A

      VariantEvidence: VHL and MTOR variants were not explicitly stated to be germline in the text but were not present in Supplementary eTable 1 where variants present in tumor/metastasis and absent in blood are listed. The number of tumor mutations (single nucleotide variants and indels) leading to nonsynonymous coding or loss-of-function (LOF) variants in the primary tumor was 160. Tumor mutations refer to those detected in the tumor but absent in the blood. In total, 116, 76, and 65 mutations were detected in each of the 3 tumor regions and from these, 41 were shared. Among the shared tumor mutations, 39 were missense variants and 2 were LOF variants caused by frameshifts. The variants affecting genes frequently mutated in ccRCC were detected in all tumor samples analyzed: VHL (c.263G>T; p.W88L), BAP1 (c.1359dup; p.E454Rfs*15), and MTOR (c.5920T>C; p.Y1974H). For a comprehensive list of somatic variants see Supplementary eTable1.

      MutationType: missense_variant;transversion

      CivicName: W88L (c.263G>T)

      MultipleGeneVariants: Germline, MTOR, c.5920T>C (p.Tyr1974His) MultipleGeneVariants: Somatic, BAP1, c.1359dup (p.Glu454Argfs*15)

      InheritancePattern:AutosomalDominant DiseaseEntity:clearcellrenalcellcarcinoma AgeOfPresentation:clearcellrenalcellcarcinoma:57 Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:263 ProteinPosition:88 AminoAcidChange:TRPtoLEU ClinVarID:N/A CAID:CA351750675 MultipleGeneVariants MutationType:missense_variant;transversion CivicName:W88L(c.263G>T) PreviousTesting:SupplementaleTable1 NoFamilyInfo SupplementalData inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    jnccn.org/view/journals/jnccn/15/11/article-p1310.xml
  18. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Sporadic phaeochromocytoma in childhood: clinical and molecular variability
    1
    1. ClingenBaseline 30 Oct 2026
      The second patient, an incidental finding, was practically asymptomatic and had a de novo germline point mutation in the VHL gene (Arg167Trp).

      PatientID: 2

      KindredID: 2

      Case: M, 10Y6M, Ethnicity Unknown

      DiseaseAssertion: adrenal pheochromocytoma

      FamilyInfo: de novo mutation found: his parents were said to have tested negative for the mutation (neither parent had this R167W mutation). All other family history was negative.

      CasePresentingHPOs: HP:0006748 (adrenal pheochromocytoma)

      CaseHPOFreeText: this patient was described to be practically asymptomatic, with an incidental finding: Diagnosed with adrenal incidentaloma, he had intermittent abdominal pain for 6 months (beginning at age 10Y). CT scan showed a left adrenal solid tumor (3x3cm) with no calcifications; I-MIBG was normal; he underwent an adrenalectomy for this pheochromocytoma.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: brain and spinal cord MRI, ophthal-moscopy, whole body CT scan and ultrasonography of the testes, showed no abnormalities.

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:DeNovoAssertion deNovoConfirmed DiseaseEntity:adrenalpheochromocytoma AgeOfPresentation:adrenalpheochromocytoma:10 Mutation:Germline AssumedRefSeq:NM_000551.3 CivicName:R167W(c.499C>T) cDNAposition:499 ProteinPosition:167 MutationType:missense_variant;transition AminoAcidChange:ARGtoTRP ClinVarID:2218 ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/16042317/
  19. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Cauda equina hemangioblastoma at L5 vertebral level related to von Hippel-Lindau disease
    1
    1. ClingenBaseline 30 Oct 2026
      PMID: 22133049

      PatientID: 1 (case)

      KindredID: 1

      Case: F, 32Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: The patient’s mother had a history of hemangioblastoma located in thoracic cord, however no testing was mentioned

      CasePresentingHPOs: HP:0001737; HP:0009713 (pancreatic cysts, spinal hemangioblastoma)

      CaseHPOFreeText: she presented with 2-month history of severe glutea and right leg pain. At 32Y, MRI showed a well-demarcated, ellipsoidal mass at the level of L5 which almost completely obliterated the spinal canal (originally thought to be a cauda equine nerve sheath tumour). Immunohistology confirmed a hemangioblastoma. MRI scans of abdomen displayed multiple cysts of the pancreatic body

      CaseNotHPOs: HP:0010797; HP:0000107 (hemangioblastoma, renal cyst)

      CaseNotHPOFreeText: There are no other tumours in brain scans; MRI scans of abdomen displayed but no change in renal

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.E94*(c.280G>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 584477 https://www.ncbi.nlm.nih.gov/clinvar/variation/584477/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: Not explicitly said to be germline. However family history gives presumption, and: “the final diagnosis of VHL is based on the VHL gene mutation analysis and the demonstration of clinical manifestation”. On immunohistochemistry, the endothelial cells were positive for CD31 and CD34, and the stromal were positive for NSE and vimentin, were negative for Ki-67/MIB-1, GFAP and AE1/AE3, EMA, S-100 and P53

      MutationType: stop_gained

      CivicName:p.E94*(c.280G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:pancreaticcysts DiseaseEntity:spinalhemangioblastoma Mutation:Germline AssumedRefSeq:NM_000551.3 CivicName:E94*(c.280G>T) cDNAposition:280 ProteinPosition:94 AminoAcidChange:GLUtoTER MutationType:stop_gained ClinVarID:584477 ClinVarID:Yes Familial inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/22133049/
  20. onlinelibrary-wiley-com.uhn.idm.oclc.org onlinelibrary-wiley-com.uhn.idm.oclc.org
    The genomic landscape of phaeochromocytoma
    1
    1. ClingenBaseline 30 Oct 2026
      All germline mutations in VHL,

      PatientID: V-PH-34T

      KindredID: 6

      Case: M, 40Y0M, Ethnicity Unknown

      DiseaseAssertion: assumed VHL

      FamilyInfo: A family history of VHL associated phenotypes was given. This patient is said to be the sibling of V-PH-33T with the germline VHL mutation: p.W117S (c.350G>C). V-PH-35T is also said to be a sibling, with the VHL mutation p.Arg161Ter.

      CasePresentingHPOs: HP:0006748; HP0010797; HP:0100565 (adrenal pheochromocytoma, hemangioblastoma, hydromyelia)

      CaseHPOFreeText: diagnosed with left adrenal phaeochromocytoma at age 40Y, surgery the same year. He also had a personal history including recurrent pheaochromocytoma and hemangioblastomas, and hydromyelia. He also had raised noradrenaline and normetanephrine levels

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: RET, SDHA, SDHB, SDHC, TMEM127

      PreviouslyPublished: Likely; 26796762 (ID: RNSH10)

      SupplementalData: Yes (see table S1 and S10)

      Variant: p.R161* (c.481C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: Patient given as ENSP00000256474.2:p.Arg161Ter/ENSP00000256474.2:p.Arg200GlyfsTer2

      ClinVarID: 2217, https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: CivicName: R161* (c.481C>T) AND R200fs (c.598del)

      MultipleGeneVariants: Germline, KIF1B, c.184-6_184-5del; Germline, KIF1B, c.608+8dup; Somatic, VHL, c.delC; Germline, VHL, c.598del (p.Arg200GlyfsTer2)

      InheritancePattern:AutosomalDominant DiseaseEntity:hydromyelia DiseaseEntity:hemangioblastoma DiseaseEntity:adrenalpheochromocytoma AgeOfPresentation:adrenalpheochromocytoma:40 Mutation:Germline AssumedRefSeq:NM_000551.3 MutationType:stop_gained ProteinPosition:161 CivicName:R161*(c.481C>T)ANDR200fs(c.598del) cDNAposition:481 AminoAcidChange:ARGtoTER SupplementalData MultipleGeneVariants MultipleVHLVariants ClinVarID:2217 ClinVarID:Yes Familial PreviousTesting:RET/SDHA/SDHB/SDHC/TMEM127 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    onlinelibrary-wiley-com.uhn.idm.oclc.org/doi/full/10.1002/path.4503
  21. onlinelibrary.wiley.com onlinelibrary.wiley.com
    Genotype–phenotype correlations in von Hippel-Lindau disease
    1
    1. ClingenBaseline 30 Oct 2026

      GroupID: 78

      DiseaseAssertion: assumed VHL

      GroupSize: 5

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: N/A

      GroupAgeRange: N/A

      GroupInfo: 5 of the 573 patients discussed in this paper were found to have identical variants. This mutation (c.496G>T) was found in 2 VHL families with 5 patients.

      GroupPresentingHPOs: pheochromocytoma; retinal capillary hemangioma; cerebellar hemangioblastoma (HP:0002666; HP:0009711; HP:0006880)

      GroupHPOFreeText: 2 patients had retinal angiomas with a mean age of diagnosis of 24Y, 2 patients had cHBs with a mean age of diagnosis of 23Y, and 4 patients had pheos with a mean age of diagnosis of 22Y,

      GroupNotHPOs: HP:0005584 (renal cell carcinoma)

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: Supplementary Table S1.

      Variant: p.V166F (c.496G>T)

      CaseProblemVariantFreeText: Paper (suppl. table) records this as c.498A>G, however this doesn't match the given protein change (p.V166F). As the Latif et al. 1993 (AFO10238) sequence given was c.709G>T, can deduce with high likelihood that this "c.498A>G" should have wrote "c.496G>T".

      LegacyVariant: N/A

      ClinVarID: 2224 https://www.ncbi.nlm.nih.gov/clinvar/variation/2224/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: V166F (c.496G>T)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:pheochromocytoma DiseaseEntity:cerebellarhemangioblastoma DiseaseEntity:retinalcapillaryhemangioma SupplementalData ExperimentalAssay Mutation:Germline RefSeq:NM_000551.2 InheritancePattern:AutosomalDominant Familial MutationType:missense_variant;transversion AminoAcidChange:VALtoPHE ProteinPosition:166 cDNAposition:496 ClinVarID:2224 ClinVarID:Yes CivicName:V166F(c.496G>T) inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    onlinelibrary.wiley.com/doi/abs/10.1002/humu.20385
  22. www.endocrinepractice.org www.endocrinepractice.org
    VHL-Related Neuroendocrine Neoplasms And Beyond: An Israeli Specialized Center Real-Life Report
    1
    1. ClingenBaseline 30 Oct 2026
      n 1996, we described a 3 generation VHL 2A kindred with 11 mutation carriers. We aim to share our experience regarding the long-term follow-up of this family

      PatientID: 12

      KindredID: 1

      Case: F, 18Y0M, Ethnicity Unknown

      DiseaseAssertion: N/A

      FamilyInfo: This patient was a member of family 1, where 14/32 total patients were diagnosed with VHL. One of which (I-32) was a mutational carrier with down syndrome. The other 13 patients had varying phenotypes, including adrenal pheochromocytoma, pancreatic endocrine tumors, liver and bone metastases, paraganglioma, cerebellar, spinal, and retinal hemangioblastomas, polycythemia, and chondrosarcoma. See Fig. 1 for family pedigree.

      CasePresentingHPOs: N/A

      CaseHPOFreeText: Patient died at age 18. Death suspected by catecholamine crisis (possible PPGL) (see table 1).

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: 8550742

      SupplementalData: N/A

      Variant: p.V166F (c.496G>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2224, https://www.ncbi.nlm.nih.gov/clinvar/variation/2224/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transversion

      CivicName: V166F (c.496G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline MutationType:missense_variant;transversion cDNAPosition:496 ProteinPosition:166 AminoAcidChange:VALtoPHE ClinVarID:2224 ClinVarID:Yes RefSeq:NM_000551.3 Familial CivicName:V166F(c.496G>T) FamilyPedigree inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    endocrinepractice.org/article/S1530-891X(20)48218-7/fulltext
  23. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Clinical and genetic characterization of pheochromocytoma in von Hippel-Lindau families: comparison with sporadic pheochromocytoma gives insight into natural history of pheochromocytoma
    1
    1. ClingenBaseline 30 Oct 2026

      GroupID/KindredID: 5959

      DiseaseAssertion:VHL

      GroupSize: 2

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: N/A

      GroupAgeRange: N/A

      GroupInfo: These two patients were from the same family (5959) and both had the same VHL gene mutations.

      GroupPresentingHPOs: HP:0002666; HP:0009711; HP:0030405 (Pheochromocytoma, Retinal capillary hemangioma, Pancreatic endocrine tumor)

      GroupHPOFreeText: One patient in this family had a pheochromocytoma and cysts (type of cyst was not specified). Both patients had retinal angioma. It is unclear how many of the patients had pancreatic endocrine tumors.

      GroupNotHPOs: HP:0005584; HP:0010797 (Renal cell carcinoma, Hemangioblastoma)

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.P81S (c.241C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: c.454C>T

      ClinVarID: 2233, https://www.ncbi.nlm.nih.gov/clinvar/variation/2233/

      CAID: N/A

      gnomAD: 0.0002179, https://gnomad.broadinstitute.org/variant/3-10183772-C-T

      VariantEvidence: Variant reported as 454, C to T (Pro to Ser), assumed to be reported in legacy nomenclature (AF010238.1) and mapped to c.241C>T, p.Pro81Ser (NM_000551.3).

      MutationType: missense_variant;transition

      CivicName: P81S (c.241C>T)

      MultipleGeneVariants: Germline, VHL, c.562C>G (p.Leu188Val)

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:pheochromocytoma DiseaseEntity:hemangioblastoma DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:pancreaticendocrinetumor Mutation:Germline AssumedRefSeq:AF010238.1 cDNAposition:241 ProteinPosition:81 AminoAcidChange:PROtoSER ClinVarID:2233 ClinVarID:Yes MutationType:missense_variant;transition CivicName:P81S(c.241C>T) Familial FamilyCohort inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/10458336/
  24. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Three novel VHL germline mutations in Korean patients with von Hippel-Lindau disease and pheochromocytomas
    1
    1. ClingenBaseline 30 Oct 2026

      PatientID: S-FPH1

      KindredID: S-FPH1

      Case: F, 60Y0M, Korean

      DiseaseAssertion: VHL

      FamilyInfo: 2 affected individuals in this family. Pheochromocytoma is noted as familial.

      CasePresentingHPOs: HP:0002666 (Pheochromocytoma)

      CaseHPOFreeText: Bilateral pheochromocytoma. Diagnosed with VHL type 2C.

      CaseNotHPOs: HP:0005584; HP:0010797 (Renal cell carcinoma, Hemangioblastoma)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: 25078357

      SupplementalData: N/A

      Variant: p.V84L (c.250G>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2236, https://www.ncbi.nlm.nih.gov/clinvar/variation/2236/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: V84L (c.250G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Korean DiseaseEntity:VHL DiseaseEntity:pheochromocytoma Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:250 ProteinPosition:84 AminoAcidChange:VALtoLEU ClinVarID:2236 ClinVarID:Yes MutationType:missense_variant;transversion CivicName:V84L(c.250G>T) Familial inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/16142346/
  25. journals.lww.com journals.lww.com
    Endocrine Pancreatic Tumors in von Hippel-Lindau Disease:... : Pancreas
    1
    1. ClingenBaseline 30 Oct 2026
      21 missense mutations

      PatientID: 15

      KindredID: 503

      Case: Sex unknown, Age unknown, French

      DiseaseAssertion: VHL

      FamilyInfo: One other member belonging to family 503 was mentioned (Patient: 7). This patient was found to have a pancreatic endocrine tumour, pheochromocytoma and renal cell carcinoma.

      CasePresentingHPOs: HP:0030405 (pancreatic endocrine tumour)

      CaseHPOFreeText: N/A

      CaseNotHPOs: HP:0002666; HP:0005584 (pheochromocytoma, renal cell carcinoma)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.P86S (c.256C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 178692 https://www.ncbi.nlm.nih.gov/clinvar/variation/178692/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence:N/A

      MutationType: missense_variant;transition

      CivicName: P86S (c.256C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant MutationType:missense_variant;transition CivicName:P86S(c.256C>T) cDNAposition:256 ProteinPosition:86 AminoAcidChange:PROtoSER ClinVarID:178692 ClinVarID:Yes Familial Mutation:Germline Ethnicity:French DiseaseEntity:VHL DiseaseEntity:pancreaticendocrinetumor AssumedRefSeq:NM_000551.3 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    journals.lww.com/pancreasjournal/fulltext/2008/07000/endocrine_pancreatic_tumors_in_von_hippel_lindau.13.aspx
  26. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Germline mutations in the new E1' cryptic exon of the VHL gene in patients with tumours of von Hippel-Lindau disease spectrum or with paraganglioma
    2
    1. ClingenBaseline 30 Oct 2026
      #8ccRCC(39)NAc.340+578C>Trs1396223560.05NANANANANAVUS

      PatientID: 8

      KindredID: 8

      Case: Sex Unknown, 39Y0M, Ethnicity Unknown

      DiseaseAssertion: clear cell renal cell carcinoma

      FamilyInfo: N/A - not stated

      CasePresentingHPOs: HP:0006770 (clear cell renal cell carcinoma)

      CaseHPOFreeText: Clear cell RCC diagnosed first at 39Y was recorded

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: Yes

      Variant: c.340+578C>T

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 849869 https://www.ncbi.nlm.nih.gov/clinvar/variation/849869/

      CAID: N/A

      gnomAD: 0.0005097 https://gnomad.broadinstitute.org/variant/3-10184449-C-T

      VariantEvidence: N/A

      MutationType: splice_site_variant; intron_variant

      CivicName: Splice Site (c.340+578C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline AssumedRefSeq:NM_000551.3 DiseaseEntity:clearcellrenalcellcarcinoma AgeOfPresentation:clearcellrenalcellcarcinoma:39 CivicName:SpliceSite(c.340+578C>T) MutationType:splice_site_variant AminoAcidChange:N/A ProteinPosition:N/A cDNAposition:N/A ClinVarID:849869 ClinVarID:Yes SupplementalData NoFamilyInfo MutationType:intron_variant inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 30 Oct 2026
      #2Carotid body PGL (34)1c.340+578C>Trs1396223560.05NANANANANAVUS

      PatientID: 2

      KindredID: 2

      Case: Sex Unknown, 35Y0M, Ethnicity Unknown

      DiseaseAssertion: paraganglioma

      FamilyInfo: N/A - not stated

      CasePresentingHPOs: HP:0100635 (Carotid Paraganglioma)

      CaseHPOFreeText: A carotid body PGL diagnosed first at 34Y was found, with follow up of a 1 year duration.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: Yes

      Variant: c.340+578C>T

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 849869 https://www.ncbi.nlm.nih.gov/clinvar/variation/849869/

      CAID: N/A

      gnomAD: 0.0005097 https://gnomad.broadinstitute.org/variant/3-10184449-C-T

      VariantEvidence: N/A

      MutationType: splice_site_variant; intron_variant

      CivicName: Splice Site (c.340+578C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline DiseaseEntity:carotidparaganglioma AgeOfPresentation:carotidparaganglioma:34 AssumedRefSeq:NM_000551.3 ClinVarID:849869 ClinVarID:Yes CivicName:SpliceSite(c.340+578C>T) MutationType:splice_site_variant AminoAcidChange:N/A cDNAposition:N/A ProteinPosition:N/A NonFamilial SupplementalData MutationType:intron_variant inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC7387210/
  27. link.springer.com link.springer.com
    Detection of large deletions in the VHL gene using a Real-Time PCR with SYBR Green
    1
    1. ClingenBaseline 30 Oct 2026
      The VHL mutation pattern includes point mutations, small deletions and large deletions.

      PatientID: VH5

      KindredID: F3

      Case: F, 26Y0M, Ethnicity Unknown

      DiseaseAssertion: pheochromocytoma

      FamilyInfo: Family history of pheo (type 2 VHL with no other lesions). two other family members are given: VH6, 54Y Male, and VH7, 25Y Male both with an isolated pheochromocytoma too.

      CasePresentingHPOs: HP:0002666 (pheochromocytoma)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: 24735130

      SupplementalData: N/A

      Variant: p.R82L (c.245G>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 526675 https://www.ncbi.nlm.nih.gov/clinvar/variation/526675/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transversion

      CivicName: R82L (c.245G>T)

      MultipleGeneVariants: N/A

      DiseaseEntity:pheochromocytoma Familial AssumedRefSeq:NM_000551.3 Mutation:Germline CivicName:R82L(c.245G>T) cDNAposition:245 ProteinPosition:82 AminoAcidChange:ARGtoLEU MutationType:missense_variant;transversion ClinVarID:526675 ClinVarID:Yes ExperimentalAssay InheritancePattern:AutosomalDominant inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    link.springer.com/article/10.1007/s10689-013-9606-2
  28. academic.oup.com academic.oup.com
    Familial pheochromocytoma associated with a novel mutation in the von Hippel-Lindau gene
    1
    1. ClingenBaseline 30 Oct 2026
      709 G-->T transversion present in all affected subjects and in four presymptomatic children.

      PatientID: II:5

      KindredID: 1

      Case: M, Age Unknown (deceased), Jewish

      DiseaseAssertion: VHL

      FamilyInfo: This kindred of Jewish-Kurdish origin consisted of 3 generations of 25 members. 7 were clinically affected subjects with pheochromocytoma (5 of which had the confirmed mutation - I:1, II:2, II:4, II:7 and II:9, as the other 2, II:5 and II:10 were said to have passed due to complications of the disease - prior to any genetic testing), and 4 others were carriers, or pre-symptomatic (III:1, III:3, III:7 and III:12). Subject 11:7 developed a cerebellar hemangioblastoma 25 yr after his initial diagnosis of pheochromocytoma, leading to the clinical diagnosis of VHL in the kindred.

      CasePresentingHPOs: HP:0002666 (pheochromocytoma)

      CaseHPOFreeText: patient had bilateral pheochromocytoma. He was said to have died of complications of the disease, and although genotype was not established prior, it is assumed that he carried the same VHL mutation

      CaseNotHPOs: HP:0005584 (renal cell carcinoma)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: 33471715

      SupplementalData: N/A

      Variant: p.V166F (c.496G>T) [assumed]

      LegacyVariant: p.V166F (c.709G>T)

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2224, https://www.ncbi.nlm.nih.gov/clinvar/variation/2224/

      CAID: N/A

      VariantEvidence: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: V166F (c.496G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:pheochromocytoma Ethnicity:Jewish Mutation:Germline AssumedRefSeq:AF010238.1 Familial FamilyPedigree ClinVarID:2224 ClinVarID:Yes cDNAposition:496 CivicName:V166F(c.496G>T) AminoAcidChange:VALtoPHE ProteinPosition:166 MutationType:missense_variant;transversion inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    academic.oup.com/jcem/article/81/1/147/2649376
  29. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Molecular genetic diagnosis of von Hippel-Lindau disease in familial phaeochromocytoma.
    1
    1. ClingenBaseline 30 Oct 2026
      V155L

      PatientID: None

      KindredID: A

      Case: F, 17Y0M, Welsh

      DiseaseAssertion: Pheochromocytoma

      FamilyInfo: The patient had a brother that presented with bilateral pheochromocytoma at 11Y. The patient also had an asymptomatic parent.

      CasePresentingHPOs: HP:0002666 (Pheochromocytoma)

      CaseHPOFreeText: The patient presented with bilateral pheochromocytoma at 17Y.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: RET

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.V84L(c.250G>T)

      LegacyVariant: p.V155L(c.463G>T)

      CaseProblemVariantFreeText: bandshift in exon 1 and genomic sequencing indicated a G>T transversion at nucleotide 463, substituting a valine for leucine at codon 155 (V155L). Leading to NM_000551.3:p.V84L(c.250G>T)

      ClinVarID: 2236, http://www.ncbi.nlm.nih.gov/clinvar/variation/2236

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: V84L(c.250G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Welsh DiseaseEntity:pheochromocytoma AgeOfPresentation:pheochromocytoma:17 Mutation:Germline RefSeq:N/A AssumedRefSeq:AF010238.1 cDNAposition:250 ProteinPosition:84 AminoAcidChange:VALtoLEU ClinVarID:Yes ClinVarID:2236 MutationType:missense_variant;transversion CivicName:V84L(c.250G>T) PreviousTesting:RET FamilyPedigree Familial inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC1051741/
  30. erc.bioscientifica.com erc.bioscientifica.com
    Overexpression of miR-210 is associated with SDH-related pheochromocytomas, paragangliomas, and gastrointestinal stromal tumours
    1
    1. ClingenBaseline 30 Oct 2026
      P1639MPCBenignVHL (p. Arg161X)NA50PosPos

      PatientID: P16

      KindredID: P16

      Case: M, 39Y0M, Ethnicity Unknown

      DiseaseAssertion: Pheochromocytoma

      FamilyInfo: N/A

      CohortInfo: Tumour samples and paired peripheral blood samples were obtained from 39 patients, consisting of 31 PCs, seven extra adrenal PGLs and one metastasis from a malignant PC previously presenting with a PC.

      CasePresentingHPOs: HP:0002666 (pheochromocytoma)

      CaseHPOFreeText: The patient had a benign pheochromocytoma measuring 50 mm at age 39.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: RET/SDHB/SDHD

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R161* (c.481C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 2217 https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: The tumour tested positive for SDHA and SHB IHC.

      MutationType: stop_gained

      CivicName: R161* (c.481C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline MutationType:stop_gained AssumedRefSeq:NM_000551.3 DiseaseEntity:pheochromocytoma AgeOfPresentation:pheochromocytoma:39 CasePreviousTesting:RET/SDHB/SDHD CivicName:R161*(c.481C>T) cDNAposition:481 ProteinPosition:161 ClinVarID:2217 ClinVarID:Yes NoFamilyInfo AminoAcidChange:ARGtoTER inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    erc.bioscientifica.com/view/journals/erc/21/3/415.xml
  31. www.scielo.br www.scielo.br
    Molecular analysis of the Von Hippel-Lindau (VHL) gene in a family with non-syndromic pheochromocytoma: the importance of genetic testing
    1
    1. ClingenBaseline 30 Oct 2026
      After initial evaluation, the family was lost to medical follow-up. However, three years later, patient II-4 was again referred to our service after a pregnancy complicated by preeclampsia. Her urinary metanephrines were repeatedly negative on two collections (0.86 µg/mg creatinine and 0.8 µg/mg creatinine; normal value: < 1.0 µg/mg creatinine). However, computerized tomography of the abdomen showed a right-sided adrenal mass; non-contrast images revealed a density of 36 Hounsfield units, findings that are highly suggestive for a pheochromocytoma (11). Moreover, this mass was also positive on MIBG scintigraphy. Echocardiography showed concentric myocardial remodeling of the left ventricle; fundoscopy and MRI of the brain were normal. She was then treated with an alpha-blocker (prazosin) in preparation for an open adrenalectomy. The histology confirmed the diagnosis of a pheochromocytoma and immunohistochemistry was only weakly positive for COX-2 (data not shown), a finding that is suggestive of a benign tumor (12).

      PatientID: II-4

      KindredID: 1

      Case: F, Age Unknown, Ethnicity Unknown

      DiseaseAssertion: Adrenal pheochromocytoma

      FamilyInfo: The patient’s brother (II-1) was found to harbor the same germline mutation the patient harbored and had bilateral adrenal pheochromocytoma at 14Y. The patient’s sister (II-2) was found to harbor the same germline mutation the patient harbored and had left adrenal pheochromocytoma at 10Y. The same germline missense mutation was found in the patient’s asymptomatic daughter (III-1). The father was not available for genetic testing because he had died, apparently secondary to a hypertensive crisis. The five other family members which underwent genetic testing did not have the mutation.

      CasePresentingHPOs: HP:0006748 (Adrenal pheochromocytoma)

      CaseHPOFreeText: The patient was originally asymptomatic, but the patient presented with preeclampsia three years after the initial study. Her urinary metanephrines were negative on two collections (0.86 µg/mg creatinine and 0.8 µg/mg creatinine). However, computerized tomography of the abdomen showed a right-sided adrenal mass, and adrenal pheochromocytoma was histologically confirmed. Immunohistochemistry was weakly positive for COX-2, so the tumor was likely benign.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.V166F (c.496G>T)

      LegacyVariant: N/A

      ClinVarID: 2224, https://www.ncbi.nlm.nih.gov/clinvar/variation/2224/

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: V166F(c.496G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:adrenalpheochromocytoma Mutation:Germline RefSeq:N/A AssumedRefSeq:NM_000551.3 cDNAposition:496 ProteinPosition:166 ClinVarID:Yes MutationType:missense_variant;transversion CivicName:V166F(c.496G>T) FamilyPedigree Familial ClinVarID:2224 AminoAcidChange:VALtoPHE DiseaseEntity:asymptomatic inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    scielo.br/j/abem/a/MbLMTLsfq6jvN3HLJt5qZHH/
  32. journals-scholarsportal-info.myaccess.library.utoronto.ca journals-scholarsportal-info.myaccess.library.utoronto.ca
    Genotype–phenotype analysis of von Hippel–Lindau syndrome in fifteen Indian families
    1
    1. ClingenBaseline 30 Oct 2026
      D1846M-- -?- ? -c.499 C[Tp.R167Wa

      PatientID:18

      KindredID: D

      Case: M, 46Y0M, Indian

      DiseaseAssertion: VHL

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0009711, HP:0002666 (retinal capillary hemangioma, pheochromocytoma)

      CaseHPOFreeText: N/A

      CaseNotHPOs: HP:0001737, HP:0010797, HP:0005584, HP:0030393 (pancreatic cyst, hemangioblastoma, renal cell carcinoma, endolymphatic sac tumor)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218 https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007 https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_transition

      CivicName: R167W(c.499C>T)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP ClinVarID:2218 MutationType:missense_variant;transition CivicName:R167W(c.499C>T) DiseaseEntity:pheochromocytoma DiseaseEntity:retinalcapillaryhemangioma InheritancePattern:AutosomalDominant Ethnicity:Indian ClinVarID:Yes NoFamilyInfo inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    journals-scholarsportal-info.myaccess.library.utoronto.ca/pdf/13899600/v14i0004/585_gaovhsifif.xml
  33. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Integrative Genetic Characterization and Phenotype Correlations in Pheochromocytoma and Paraganglioma Tumours
    1
    1. ClingenBaseline 30 Oct 2026
      11PCCM21+VHL40/30Multiple−− VHL 3Germlinec.499C>Tp.Arg167TrpPathogenic

      PatientID: 11

      KindredID: 2

      Case: M, 21Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: Patient has 2 siblings (patients 10 and 12) with the same mutation and pheochromocytoma.

      CasePresentingHPOs: HP:0002666 (Pheochromocytoma)

      CaseHPOFreeText: Bilateral pheochromocytoma (40mm and 30mm)

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: SDHB (NM_003000.2), SDHC (NM_003001.3), SDHD (NM_003002.2), SDHAF2 (NM_017841.2), RET (exons 10–11 and 13–16, NM_020975.4), TMEM127 (NM_017849.3), MAX (NM_002382.3).

      PreviouslyPublished: N/A

      SupplementalData: Table 2

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T

      VariantEvidence: Loss of heterozygosity could be detected in tumour DNA.

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:pheochromocytoma AgeOfPresentation:pheochromocytoma:21 Mutation:Germline RefSeq:NM_000551.3 cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP ClinVarID:2218 ClinVarID:Yes MutationType:missense_variant;transition CivicName:R167W(c.499C>T) PreviousTesting:SDHB/SDHC/SDHD/SDHAF2/RET/TMEM127/MAX Familial SupplementalData inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC3899286/
  34. thejns-org.myaccess.library.utoronto.ca thejns-org.myaccess.library.utoronto.ca
    Ruptured intracranial aneurysm associated with von Hippel–Lindau syndrome: a molecular link?
    1
    1. ClingenBaseline 30 Oct 2026
      he patient's mother tested positive for the same point mutation, but neuroimaging showed that she was unaffected by the disease that affected her daughter.

      PatientID: 2

      KindredID: 1

      Case: F, Age Unknown, Ethnicity Unknown

      DiseaseAssertion: Asymptomatic

      FamilyInfo: The proband (designated as 'Patient 1') presented with the same germline mutation as her mother (this patient, designated as 'Patient 2'). However, neuroimaging showed that this patient was unaffected by the same disease (spinocerebellar hemangioblastomas) as her daughter. There was no other family history of similar diseases/complaints. In contrast to her mother, the proband presented with subarachnoid hemorrhage at age 17. Six years later (age 23), she presented with cystic lesions in the cerebellar vermis and cervicomedullary region, diagnosed as spinocerebellar hemangioblastomas through tumor biopsy. She underwent a total excision of these tumors.

      CasePresentingHPOs: N/A

      CaseHPOFreeText:

      CaseNotHPOs: HP:0009713; HP:0006880 (Spinal hemangioblastoma, Cerebellar hemangioblastoma)

      CaseNotHPOFreeText: Neuroimaging showed that this patient was unaffected by the same disease (spinocerebellar hemangioblastomas) as her daughter.

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.P86S (c.256C>T)

      LegacyVariant: c.469C>T

      CaseProblemVariantFreeText: N/A

      ClinVarID: 178692, https://www.ncbi.nlm.nih.gov/clinvar/variation/178692/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType:missense_variant;transition

      CivicName: P86S (c.256C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:asymptomatic Mutation:Germline AssumedRefSeq:AF010238.1 cDNAposition:256 ProteinPosition:86 AminoAcidChange:PROtoSER ClinVarID:178692 MutationType:missense_variant;transition CivicName:P86S(c.256C>T) Familial inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    thejns-org.myaccess.library.utoronto.ca/pediatrics/view/journals/j-neurosurg-pediatr/104/2/article-p90.xml
  35. www.liebertpub.com www.liebertpub.com
    VHL Germline Mutations in Argentinian Patients with Clinical Diagnoses or Single Typical Manifestations of Type 1 von Hippel-Lindau Disease
    1
    1. ClingenBaseline 30 Oct 2026
      nonsense mutations (6/16)

      PatientID: 9

      KindredID: 9

      Case: 25Y0M, Sex Unknown, Argentinian

      DiseaseAssertion: VHL

      FamilyInfo: No family history

      CasePresentingHPOs: HP:0010797; HP:0005584; HP:0001737; HP:0000107 (hemangioblastoma; renal cell carcinoma; pancreatic cysts; renal cyst)

      CaseHPOFreeText: Aged 25Y at diagnosis (genetic testing); fulfils type 1 VHL clinical diagnosis. CNS angiomas diagnosed at 22, ccRCC at 22Y, renal cysts and pancreatic cysts at 22Y (See Table 1 & 2).

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R161* (c.481C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2217 https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: R161* (c.481C>T)

      MultipleGeneVariants: N/A

      Ethnicity:Argentinian DiseaseEntity:VHL AgeOfPresentation:hemangioblastoma:22 AgeOfPresentation:clearcellrenalcellcarcinoma:22 AgeOfPresentation:renalcyst:22 AgeOfPresentation:pancreaticcysts:22 Mutation:Germline RefSeq:NM_000551.3 CivicName:R161*(c.481C>T) cDNAposition:481 ProteinPosition:161 AminoAcidChange:ARGtoTER MutationType:stop_gained ClinVarID:2217 ClinVarID:Yes NonFamilial DiseaseEntity:hemangioblastoma DiseaseEntity:clearcellrenalcellcarcinoma DiseaseEntity:renalcyst DiseaseEntity:pancreaticcysts ExperimentalAssay inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    liebertpub.com/doi/10.1089/gtmb.2016.0204
  36. eje.bioscientifica.com eje.bioscientifica.com
    Germline VHL gene mutations in Hungarian families with von Hippel–Lindau disease and patients with apparently sporadic unilateral pheochromocytomas
    1
    1. ClingenBaseline 30 Oct 2026
      Cousin 2–383929–

      PatientID: None (Cousin 2)

      KindredID: G

      Case: Sex Unknown, 38Y0M, Hungarian

      DiseaseAssertion: Assumed VHL

      FamilyInfo: Large VHL family spanning five generations. The index patient presented with pheochromocytoma, renal cell carcinoma as well as spinal cord, cerebellar, and medulla oblongata hemangioblastomas. Her parents showed no clinical, biochemical, or radiological evidence of the disease, but VHL-associated tumors were detected in five other family members (bilateral renal cell carcinomas in one, renal cysts in one, spinal cord, cerebellar, and medulla oblongata hemangioblastomas in three, retinal hemangioblastomas in four, and pheochromocytomas in two family members).

      CasePresentingHPOs: HP:0010797; HP:0009711; HP:0002666 (Hemangioblastoma, Retinal capillary hemangioma, Pheochromocytoma)

      CaseHPOFreeText: Presented with CNS hemangioblastoma at age 38, pheochromocytoma at age 39 and retinal hemangioblastoma at age 29. No VHL diagnosis noted but assumed to have VHL based on genetic, clinical and familial findings.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: 18416845

      SupplementalData: N/A

      Variant: p.S80I (c.239G>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 625229, https://www.ncbi.nlm.nih.gov/clinvar/variation/625229/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: Variant reported as S80I and cDNA change was mapped to c.239G>T.

      MutationType: missense_variant;transversion

      CivicName: S80I (c.239G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Hungarian DiseaseEntity:AssumedVHL DiseaseEntity:hemangioblastoma DiseaseEntity:pheochromocytoma AgeOfPresentation:hemangioblastoma:38 AgeOfPresentation:pheochromocytoma:39 Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:239 ProteinPosition:80 AminoAcidChange:SERtoILE ClinVarID:625229 ClinVarID:Yes MutationType:missense_variant;transversion CivicName:S80I(c.239G>T) Familial DiseaseEntity:retinalcapillaryhemangioma AgeOfPresentation:retinalcapillaryhemangioma:29 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    eje.bioscientifica.com/view/journals/eje/161/3/495.xml
  37. onlinelibrary-wiley-com.uhn.idm.oclc.org onlinelibrary-wiley-com.uhn.idm.oclc.org
    Frequency of Von Hippel-Lindau germline mutations in classic and non-classic Von Hippel-Lindau disease identified by DNA sequencing, Southern blot analysis and multiplex ligation-dependent probe amplification
    1
    1. ClingenBaseline 30 Oct 2026
      10 c.388G>T p.Val130Phe p.V130F Familial VHL

      GroupID/ KindredID: 10

      DiseaseAssertion: VHL

      GroupSize: 5

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: N/A

      GroupAgeRange: N/A

      GroupInfo: 5 registrants belonging to the same family (10) have the germline VHL mutation.

      GroupPresentingHPOs:HP:0009711; HP:0010797; HP:0001737; HP:0005584; HP:0000107 (retinal capillary hemangioma, hemangioblastoma, pancreatic cysts, renal cell carcinoma, renal cyst)

      GroupHPOFreeText: 4 had retinal hemangioblastomas, 3 had CNS hemangioblastomas, 2 had renal cell carcinoma, with 4 renal cysts and 3 had pancreatic cysts

      GroupNotHPOs: HP:0002666 (pheochromocytoma)

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: Previously reported, HGMD (Human Gene Mutation Database: http://uwcmml1s.uwcm.ac.uk/uwcm/mg/search/120488.html)

      SupplementalData: N/A

      Variant: p.V130F (c.388G>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 496061 https://www.ncbi.nlm.nih.gov/clinvar/variation/496061/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: V130F (c.388G>T)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:hemangioblastoma DiseaseEntity:pancreaticcysts DiseaseEntity:renalcellcarcinoma DiseaseEntity:renalcyst Familial FamilyCohort ClinVarID:496061 ClinVarID:Yes AminoAcidChange:VALtoPHE ProteinPosition:130 CivicName:V130F(c.388G>T) cDNAposition:388 MutationType:missense_variant;transversion Mutation:Germline RefSeq:NM_000551.2 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    onlinelibrary-wiley-com.uhn.idm.oclc.org/doi/full/10.1111/j.1399-0004.2007.00827.x
  38. Oct 2026
  39. nyaspubs.onlinelibrary.wiley.com nyaspubs.onlinelibrary.wiley.com
    Genetic mutation screening in an italian cohort of nonsyndromic pheochromocytoma/paraganglioma patients
    1
    1. ClingenBaseline 29 Oct 2026
      Read the full text

      PatientID: 10

      KindredID: 10

      Case: Sex Unknown, 35Y0M, Italian

      DiseaseAssertion: paraganglioma

      FamilyInfo: None - said NOT to have a positive family history. Apparently sporadic

      CasePresentingHPOs: HP:0002668 (paraganglioma)

      CaseHPOFreeText: left para-adrenal PGL with an age of first diagnosis of 35Y

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.P81L (c.242C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 36899 https://www.ncbi.nlm.nih.gov/clinvar/variation/36899/

      CAID: N/A

      gnomAD: 0.000004349 https://gnomad.broadinstitute.org/variant/3-10183773-C-T

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: P81L (c.242C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Italian DiseaseEntity:paraganglioma AgeOfPresentation:paraganglioma:35 Mutation:Germline AssumedRefSeq:NM_000551.3 ProteinPosition:81 cDNAposition:242 MutationType:missense_variant;transition AminoAcidChange:PROtoLEU ClinVarID:36899 ClinVarID:Yes CivicName:P81L(c.242C>T) NonFamilial inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1196/annals.1353.016
  40. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Development of synchronous VHL syndrome tumors reveals contingencies and constraints to tumor evolution
    1
    1. ClingenBaseline 29 Oct 2026
      Clinical case reportA 32-year-old male presented with hematuria. Ultrasound demonstrated multiple renal cysts and the initial diagnosis was polycystic kidney disease. However, the cysts enlarged during a surveillance period of one year, leading to computed tomography imaging demonstrating a locally advanced right renal tumor, and two tumors in the left kidney (Figure 1). Further investigation revealed capillary retinal angiomas and hemangiomas of the brain and spine typical of VHL disease, and he was diagnosed with a de novo, germline nonsense mutation in exon 3 of the VHL gene. At the age of 33, the patient underwent a radical right nephrectomy; histopathological examination confirmed a single stage 3, Fuhrman grade 3 ccRCC (pT3aN0M0). Six months later, there was progression in the left kidney and he was treated with partial left nephrectomy to remove both tumors. Both were stage 1 ccRCCs with a maximum Fuhrman grade of 2 (pT1aN0M0). At the time of this report, the patient remains in complete remission.

      PatientID: None

      KindredID: 1

      Case: M, 32Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0000790, HP:0009711, HP:0000107, HP:0009713, HP:0010797, HP:0006770 (hematuria, retinal capillary hemangioma, renal cyst, spinal hemangioblastoma, hemangioblastoma, clear cell renal cell carcinoma)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R120*(c.358A>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: N/A

      CAID: CA351753732 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.358A%3ET

      gnomAD: N/A

      VariantEvidence: All tumor regions also displayed 3p LOH.

      MutationType: stop_gained

      CivicName: R120*(c.358A>T)

      MultipleGeneVariants: Somatic, VHL, not described

      MutationType:stop_gained Mutation:Germline AssumedRefSeq:NM_000551.3 DiseaseEntity:VHL NoFamilyInfo DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:renalcyst DiseaseEntity:spinalhemangioblastoma DiseaseEntity:hemangioblastoma DiseaseEntity:clearcellrenalcellcarcinoma AgeOfPresentation:clearcellrenalcellcarcinoma:32 AgeOfPresentation:renalcyst:32 cDNA:358 ProteinPosition:120 CAID:CA351753732 ClinVarID:N/A CivicName:R120*(c.358A>T) MultipleVHLVariants InheritancePattern:DeNovoAssertion AminoAcidChange:ARGtoTER ExperimentalAssay inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC4166471/
  41. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Germline Pathogenic Variants Identified by Targeted Next-Generation Sequencing of Susceptibility Genes in Pheochromocytoma and Paraganglioma
    1
    1. ClingenBaseline 29 Oct 2026
      2 MA35/MPheochromocytoma (Bilateral)Father, sisterVHL{"type":"entrez-nucleotide","attrs":{"text":"NM_000551.4","term_id":"1779521775"}}NM_000551.4:c.481C>Tp.(Arg161Ter)rs5030818

      PatientID: 2 MA

      KindredID: 2

      Case: M, 35Y0M, Ethnicity Unknown

      DiseaseAssertion: Pheochromocytoma

      FamilyInfo: Patient had two other affected family members: their father and sister. It does not describe how they were affected nor any diagnosis or variant.

      CasePresentingHPOs: HP:0002666 (Pheochromocytoma)

      CaseHPOFreeText: Patient had bilateral pheochromocytoma

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: RET, SDHB, SDHD, TMEM127

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R161*(c.481C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2217 https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: R161*(c.481C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline RefSeq:NM_000551.4 DiseaseEntity:pheochromocytoma Familial CivicName:R161*(c.481C>T) cDNAposition:481 MutationType:stop_gained ProteinPosition:161 AminoAcidChange:ARGtoTER ClinVarID:2217 ClinVarID:Yes PreviousTesting:RET/SDHB/SDHD/TMEM127 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC7969383/
  42. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Genetic and Clinical Profiles of Pheochromocytoma and Paraganglioma: A Single Center Study
    1
    1. ClingenBaseline 29 Oct 2026
      92VHLE3c.499C>Tp.R167WPP7987306M9922Nobil-PCC,R- PGL5No

      PatientID: 92

      KindredID: 92

      Case: M, 31Y0M, Chinese (East Asian)

      DiseaseAssertion: Assumed VHL

      FamilyInfo: No family history.

      CasePresentingHPOs: Pheochromocytoma; Paraganglioma (HP:0002666; HP:0002668)

      CaseHPOFreeText: retroperitoneal paraganglioma and bilateral pheochromocytoma, with a biggest tumor size of 5cm. Age of onset and diagnosis at 9Y. 22 years later they were confirmed with a genetic mutation

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: MAX, NF1, RET, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: Described as a pathogenic variant, according to the ACMG guidelines at the time of publication.

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline RefSeq:NM_000551.3 DiseaseEntity:pheochromocytoma DiseaseEntity:paraganglioma AgeOfPresentation:pheochromocytoma:9 AgeOfPresentation:paraganglioma:9 NonFamilial Ethnicity:Chinese Ethnicity:EastAsian CivicName:R167W(c.499C>T) cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP MutationType:missense_variant;transition PreviousTesting:MAX/RET/NF1/SDHA/SDHB/SDHC/SDHD/SDHAF2/TMEM127 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC7761866/
  43. www.karger.com www.karger.com
    Germline Mutation in the von Hippel-Lindau Gene in Kuwait
    1
    1. ClingenBaseline 29 Oct 2026

      PatientID: I-1

      KindredID: 1

      Case: F, Age Unknown (deceased), Persian

      DiseaseAssertion: VHL

      FamilyInfo: Multigenerational Kuwaiti family with Arabian and Persian genetic admixture. Thirteen members of the family had been clinically diagnosed as having VHL. Patient 1-I had 6 children, 5 of which were found with VHL and the p.W117C mutation. 7/20 of her grandchildren also found to have VHL and the same mutation.

      CasePresentingHPOs: HP:0010797; HP:0006770 (hemangioblastoma; clear cell renal cell carcinoma)

      CaseHPOFreeText: Member had clear cell renal carcinomas that were the main cause of mortality, in addition to hemangioblastomas

      CaseNotHPOs: HP:0002666 (pheochromocytoma)

      CaseNotHPOFreeText: Lacked evidence of any pheos.

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.W117C (c.351G>T)

      LegacyVariant: p.Trp117Cys (c.564G>T)

      CaseProblemVariantFreeText: N/A

      ClinVarID: 167827 https://www.ncbi.nlm.nih.gov/clinvar/variation/167827/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: W117C (c.351G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Persian DiseaseEntity:VHL DiseaseEntity:clearcellrenalcellcarcinoma DiseaseEntity:hemangioblastoma Mutation:Germline RefSeq:AF010238.1 cDNAposition:351 ProteinPosition:117 AminoAcidChange:TRPtoCYS MutationType:missense_variant;transversion CivicName:W117C(c.351G>T) ClinVarID:167827 FamilyPedigree Familial ExperimentalAssay ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    karger.com/Article/Abstract/141504
  44. onlinelibrary.wiley.com onlinelibrary.wiley.com
    Genotype-phenotype correlation in von Hippel-Lindau disease
    1
    1. ClingenBaseline 29 Oct 2026
      1 (100)

      GroupID: 41

      Case: Sex Unknown, Age Unknown, Ethnicity Unknown

      DiseaseAssertion: VHL

      CohortInfo: a retrospective cohort study from an eye centre in Germany involved 148 VHL patients and their genetic data involved in retinal capillary hemangiomas.

      CasePresentingHPOs: HP:0009711 (retinal capillary hemangioma)

      CaseHPOFreeText: This individual patient was the only one discussed with this mutation. They had retinal hemangiomas; Other VHL manifestations were discussed but not per- variant.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: Yes - Supplementary Table S1

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      GroupProblemVariantFreeText: N/A

      ClinVarID: 2218 https://www.ncbi.nlm.nih.gov/clinvar/variation/2218

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_variant; transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline AssumedRefSeq:NM_000551.3 DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma cDNAposition:499 CivicName:R167W(c.499C>T) ProteinPosition:167 AminoAcidChange:ARGtoTRP MutationType:missense_variant;transition ClinVarID:2218 ClinVarID:Yes NoFamilyInfo SupplementalData inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    onlinelibrary.wiley.com/doi/10.1111/aos.14843
  45. www-sciencedirect-com.uhn.idm.oclc.org www-sciencedirect-com.uhn.idm.oclc.org
    Denaturing High Performance Liquid Chromatography Detection of SDHB, SDHD, and VHL Germline Mutations in Pheochromocytoma
    2
    1. ClingenBaseline 29 Oct 2026
      c.499C > T

      PatientID: None

      KindredID: 13

      Case: age, sex, ethnicity unknown

      DiseaseAssertion: Unknown

      FamilyInfo: N/A

      CasePresentingHPOs: N/A

      CaseHPOFreeText: Described as a positive control but not stated anything further

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: Likely previously published - not clear where the controls came from/ how they were used.

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T

      VariantEvidence: N/A

      MutationType: missense_variant; transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline RefSeq:NM_000551.3 ProteinPosition:167 CivicName:R167W(c.499C>T) cDNAposition:499 AminoAcidChange:ARGtoTRP MutationType:missense_variant;transition ClinVarID:2218 ClinVarID:Yes NoFamilyInfo inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 29 Oct 2026
      c.250G > T(p.Val84Leu)

      PatientID: None

      KindredID: 1

      Case: age, sex, ethnicity unknown

      DiseaseAssertion: pheochromocytoma

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0002666 (pheochromocytoma)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.V84L (c.250G>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2236 https://www.ncbi.nlm.nih.gov/clinvar/variation/2236/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence:N/A

      MutationType: missense_variant; transversion

      CivicName: V84L (c.250G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline RefSeq:NM_000551.3 DiseaseEntity:pheochromocytoma ClinVarID:2236 ProteinPosition:84 cDNAposition:250 AminoAcidChange:VALtoLEU CivicName:V84L(c.250G>T) MutationType:missense_variant;transversion ClinVarID:Yes NoFamilyInfo inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    www-sciencedirect-com.uhn.idm.oclc.org/science/article/pii/S0022480408005271
  46. cancerres.aacrjournals.org cancerres.aacrjournals.org
    Telomere Shortening Is Associated with Genetic Anticipation in Chinese Von Hippel–Lindau Disease Families
    3
    1. ClingenBaseline 29 Oct 2026
      c.481C>T p.Arg161Stop

      PatientID: None (proband 15)

      KindredID: 15

      Case: M, 36Y0M, Chinese

      DiseaseAssertion: VHL

      FamilyInfo: Father had died before diagnosis therefore no DNA sample available; He presented with CNS hemangioblastomas at the age of 42.

      CasePresentingHPOs: HP:0010797; HP:0005584; HP:0001737; HP:0009715; HP:0030393 (hemangioblastoma, renal cell carcinoma, pancreatic cysts, papillary cystadenoma of the epididymis, endolymphatic sac tumor)

      CaseHPOFreeText: Patient presented with hemangioblastoma at age 29, renal cell carcinoma at age 29, pancreatic cysts at age 36, endolymphatic sac tumor at age 33, papillary cystadenoma of the epididymis at age 29.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R161* (c.481C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 2217 https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: R161* (c.481C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Chinese DiseaseEntity:VHL DiseaseEntity:hemangioblastoma DiseaseEntity:renalcellcarcinoma DiseaseEntity:pancreaticcysts DiseaseEntity:papillarycystadenomaoftheepididymis DiseaseEntity:endolymphaticsactumor AgeOfPresentation:hemangioblastoma:29 AgeOfPresentation:renalcellcarcinoma:29 AgeOfPresentation:endolymphaticsactumor:33 AgeOfPresentation:papillarycystadenomaoftheepididymis:29 Mutation:Germline AssumedRefSeq:NM_000551.3 ClinVarID:2217 ClinVarID:Yes AminoAcidChange:ARGtoTER MutationType:stop_gained AgeOfPresentation:pancreaticcysts:36 ExperimentalAssay Familial CivicName:R161*(c.481C>T) cDNAposition:481 ProteinPosition:161 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 26 Oct 2026
      c.269A>T p.Asn90Ile

      PatientID: II:3 (proband 4)

      KindredID: 4

      Case: M, 38Y0M, Chinese

      DiseaseAssertion: VHL

      FamilyInfo: Patient’s mother (I:1) was found with the same mutation and RCC at 63Y. The proband’s brother (II:1) died before diagnosis; thus no DNA sample available. He presented with hemangioblastoma at 19Y

      CasePresentingHPOs: HP:0010797; HP:0009711 (hemangioblastoma, retinal capillary hemangioma)

      CaseHPOFreeText: patient had hemangioblastoma at 22Y and retinal capillary hemangioma at 32Y

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.N90I (c.269A>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 223172 https://www.ncbi.nlm.nih.gov/clinvar/variation/223172/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transversion

      CivicName: N90I (c.269A>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Chinese DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:hemangioblastoma AgeOfPresentation:hemangioblastoma:22 AgeOfPresentation:retinalcapillaryhemangioma:32 ClinVarID:223172 ClinVarID:Yes ExperimentalAssay Familial FamilyPedigree AssumedRefSeq:NM_000551.3 Mutation:Germline ProteinPosition:90 cDNAposition:269 CivicName:N90I(c.269A>T) AminoAcidChange:ASNtoILE MutationType:missense_variant;transversion inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    3. ClingenBaseline 25 Oct 2026
      c.499C>T p.Arg167Trp

      PatientID: II:4 (proband 5’s sister 2)

      KindredID: 5

      Case: F, 34Y0M, Chinese

      DiseaseAssertion: VHL

      FamilyInfo: Her father and two sisters presented with this same mutation. The father had RCC diagnosed at 54Y. The one sister (II:3) had had pancreatic tumors at 36Y and hemangioblastomas at 38Y. The brother (II:1) appeared to be non-affected, while the other sister (II:2) had hemangioblastoma, renal cell carcinoma, pancreatic cysts, and Papillary cystadenoma of the epididymis diagnosed at 37Y; and pheochromocytoma at 39Y

      CasePresentingHPOs: HP:0009711 (retinal capillary angiomas)

      CaseHPOFreeText: had retinal angiomas at 34Y

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 2218 (https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/)

      CAID: N/A

      gnomAD: 0.000007954 https://gnomad.broadinstitute.org/variant/3-10191506-C-T

      VariantEvidence: N/A

      MutationType: missense_variant; transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Chinese DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma AgeOfPresentation:retinalcapillaryhemangioma:34 ClinVarID:2218 ClinVarID:Yes ExperimentalAssay Familial FamilyPedigree AssumedRefSeq:NM_000551.3 Mutation:Germline ProteinPosition:167 CivicName:R167W(c.499C>T) cDNAposition:499 AminoAcidChange:ARGtoTRP MutationType:missense_variant;transition inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    cancerres.aacrjournals.org/content/74/14/3802
  47. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    von Hippel-Lindau disease: renal tumors less than 3 cm. can metastasize
    1
    1. ClingenBaseline 29 Oct 2026

      PatientID: None (Daughter)

      KindredID: 1

      Case: F, Age Unknown, Ethnicity Unknown

      DiseaseAssertion: Asymptomatic

      FamilyInfo: The patient's mother had pancreatic islet cell adenoma, renal cell carcinoma, extraadrenal pheochromocytoma, and spinal cord lesion. Her brother had the same VHL gene mutation.

      CasePresentingHPOs: N/A

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.P86L (c.257C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 182977, https://www.ncbi.nlm.nih.gov/clinvar/variation/182977/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: P86L (c.257C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline AssumedRefSeq:NM_000551.3 MutationType:missense_variant;transition Familial DiseaseEntity:Asymptomatic cDNAposition:257 ProteinPosition:86 ClinVarID:182977 ClinVarID:Yes CivicName:P86L(c.257C>T) AminoAcidChange:PROtoLEU inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/11257676/
  48. journals.lww.com journals.lww.com
    PARS PLANA VITRECTOMY IN ADVANCED CASES OF VON... : RETINA
    1
    1. ClingenBaseline 29 Oct 2026
      detected point germline vhl mutations in 14 patients

      PatientID: 21

      KindredID: 21

      Case: 23Y0M, sex unknown, ethnicity unknown

      DiseaseAssertion: VHL

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0010797; HP:0009711 (hemangioblastoma; retinal capillary hemangioma)

      CaseHPOFreeText: See Table 1&2 for retinal capillary hemangioma information

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: c.464-1G>T

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 223221 https://www.ncbi.nlm.nih.gov/clinvar/variation/223221/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: Stated in paper as “IVS2-1G>T”

      MutationType: splice_site_variant

      CivicName: Splice Site (c.464-1G>T)

      MultipleGeneVariants: N/A

      DiseaseEntity:hemangioblastoma DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:VHL cDNAposition:464 ClinVarID:223221 ClinVarID:Yes CivicName:SpliceSite(c.464-1G>T) MutationType:splice_site_variant AssumedRefSeq:NM_000551.3 Mutation:Germline InheritancePattern:AutosomalDominant inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    journals.lww.com/retinajournal/fulltext/2016/02000/pars_plana_vitrectomy_in_advanced_cases_of_von.13.aspx
  49. link.springer.com link.springer.com
    Germline mutations in the von Hippel–Lindau disease (VHL) gene in mainland Chinese families
    1
    1. ClingenBaseline 29 Oct 2026
      5 nonsenses

      GroupID/ KindredID: 3

      DiseaseAssertion: assumed VHL

      GroupSize: 6

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: Chinese

      GroupAgeRange: N/A

      GroupInfo: With a family history, 6 family members were recorded in this group with the given mutation.

      GroupPresentingHPOs: HP:0010797; HP:0005584; HP:0001732 (hemangioblastoma; renal cell carcinoma; pancreatic lesion)

      GroupHPOFreeText: 5 members had CNS hemangioblastomas, 1 member had RCC, and 1 had pancreatic cysts or tumors (an abnormality of the pancreas)

      GroupNotHPOs: HP:0009711; HP:0002666 (retinal capillary hemangioma, pheochromocytoma)

      GroupNotHPOFreeText: No family members appeared to have the above manifestation.

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.Q73* (c.217C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: p.Q73* (c.430C>T)

      ClinVarID: 223164 https://www.ncbi.nlm.nih.gov/clinvar/variation/223164/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: Q73* (c.217C>T)

      MultipleGeneVariants: N/A

      Mutation:Germline DiseaseEntity:VHL DiseaseEntity:hemangioblastoma DiseaseEntity:renalcellcarcinoma DiseaseEntity:abnormalityofthepancreas RefSeq:AF010238.1 ProteinPosition:73 MutationType:stop_gained CivicName:Q73*(c.217C>T) cDNAposition:217 AminoAcidChange:GLNtoTER ClinVarID:223164 ClinVarID:Yes Ethnicity:Chinese Familial FamilyCohort InheritancePattern:AutosomalDominant inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    link.springer.com/article/10.1007/s00432-008-0399-x
  50. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Somatostatin receptor expression on von Hippel-Lindau-associated hemangioblastomas offers novel therapeutic target
    1
    1. ClingenBaseline 29 Oct 2026
      A 64-year-old female with a germline VHL missense mutation (R167W), a known large suprasellar hemangioblastoma, and history of right eye enucleation presented with worsening vision of her remaining left eye. The patient had a past history of severe VHL disease with bilateral clear cell renal cell carcinomas, bilateral pheochromocytomas, pancreatic cysts, retinal HBs, and multiple CNS HBs. Neurological exam was significant for Romberg sign and mild dysmetria of bilateral upper extremities. Left eye extraocular movements and pupillary reaction intact. A visual field test of the left eye revealed new onset inferior temporal quadrantanopsia. Magnetic resonance imaging confirmed a slowly growing (3.45 cm3) suprasellar hemangioblastoma within the circle of Willis with increased optic tract edema and compression of the optic chiasm (Fig. 3A).Open in a separate windowFigure 3Symptomatic, surgically unresectable VHL-HB treated with octreotide.(A) T1 magnetic resonance image with contrast of 64 year-old female patient with germline VHL missense mutation presents with a 3.45 cm3 suprasellar HB. (B) 68GA-DOTATATE PET/CT imaging of suprasellar HB showing avid 68GA-DOTATATE uptake. (C) 68Ga-DOTATATE-PET imaging at presentation and 6 months after octreotide treatment (D). The pituitary stalk HB exhibits diminished uptake of 12.0 SUV compared to 22.6 SUV in initial study. Central photopenia also noted, indicative of necrotic process. (E) Tumor volume was measured using Osirix® software on FLAIR images. Seven images were analyzed, with the first image acquired just prior to initiation of Octreotide treatment. Measurements in cm3. (F) Visual field analysis of patient’s left visual field prior to starting octreotide treatment (left) and 6 months after beginning treatment.The newly symptomatic suprasellar mass was deemed inoperable due to the location (suprasellar, within the circle of Willis), her extensive co-morbidities, and the risk of loss of vision in her remaining eye with an attempted surgical resection. Whole body 68Ga-DOTATATE-PET revealed that the suprasellar mass was avid for DOTATATE (maximum standard uptake value (SUVMax) = 22.6) (Fig. 3B and C). As such, octreotide was initiated off label with a trial dosing of 20 μg daily subcutaneously for two weeks. Following this, she was prescribed long-acting Octreotide-LAR 30 mg by intramuscular injection, once a month, for 9 months. On Octreotide-LAR, she reported diarrhea managed with increased pancrealipase dosing and an increased insulin requirement. Follow up 68Ga-DOTATATE-PET imaging was done 6 months after primary scans and more than one month after her most recent octreotide dose. These images revealed maximum SUVMax of 12.0, compared to the initial SUVMax of 22.6 prior to starting treatment. Moreover, the 6 month follow up scan revealed central tumor photopenia, indicative of necrosis (Fig. 3D). As a reference, the pituitary uptake initially measured 24.9 SUV and 6 months after treatment measured 50.3 SUV. Serial FLAIR MRI images were acquired periodically throughout octreotide treatment and revealed a steady decline in the volume of the suprasellar mass from 3.45 cm3 to 2.54 cm3 with 9 months of Octreotide-LAR therapy (Fig. 3E). Furthermore, visual field analysis remained stable with continuous therapy (Fig. 3F).

      PatientID: None

      KindredID: 1

      Case: F, 64Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0010797; HP:0000504; HP:0006770; HP:0002666; HP:0001737; HP:0009711; HP:0002403; HP:0020036; HP:0000969; HP:0025163 (Hemangioblastoma, Abnormality of vision, Clear cell renal cell carcinoma, Pheochromocytoma, Pancreatic cysts, Retinal capillary hemangioma, Positive Romberg sign, Upper limb dysmetria, Edema, Abnormality of optic chiasm morphology)

      CaseHPOFreeText: Presented at age 64 with a known large suprasellar hemangioblastoma, and history of right eye enucleation presented with worsening vision of her remaining left eye. The patient had a past history of severe VHL disease with bilateral clear cell renal cell carcinomas, bilateral pheochromocytomas, pancreatic cysts, retinal HBs, and multiple CNS HBs. Neurological exam was significant for Romberg sign and mild dysmetria of bilateral upper extremities. A visual field test of the left eye revealed new onset inferior temporal quadrantanopsia. Magnetic resonance imaging confirmed a slowly growing suprasellar hemangioblastoma within the circle of Willis with increased optic tract edema and compression of the optic chiasm.

      CaseNotHPOs: HP:0007686; HP:0000496 (Abnormal pupillary function, Abnormality of eye movement)

      CaseNotHPOFreeText: Left eye extraocular movements and pupillary reaction intact.

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T

      VariantEvidence: VHL-HBs demonstrated strong expression patterns for all receptor subtypes except SSTR3 (more info available in “Results”).

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:clearcellrenalcellcarcinoma DiseaseEntity:pheochromocytoma DiseaseEntity:pancreaticcysts DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:hemangioblastoma DiseaseEntity:abnormalityofvision DiseaseEntity:positiverombergsign DiseaseEntity:upperlimbdysmetria DiseaseEntity:edema DiseaseEntity:abnormalityofopticchiasmmorphology AgeOfPresentation:hemangioblastoma:64 AgeOfPresentation:abnormalityofvision:64 AgeOfPresentation:positiverombergsign:64 AgeOfPresentation:upperlimbdysmetria:64 AgeOfPresentation:edema:64 AgeOfPresentation:abnormalityofopticchiasmmorphology:64 Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP ClinVarID:2218 ClinVarID:Yes MutationType:missense_variant;transition CivicName:R167W(c.499C>T) NoFamilyInfo inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC5240113/
  51. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Sequencing of Von Hippel-Lindau (VHL) Gene from Genomic DNA for Mutation Detection in Italian Patients
    4
    1. ClingenBaseline 29 Oct 2026
      In the second case, the proband II/3 with R167W mutation (Figure 2) inherited the VHL mutated gene from his father (Figure 2, I/1), who had haemangioblastoma.

      PatientID: I/1

      KindredID: 2

      Case: M, Age Unknown, Italian

      DiseaseAssertion: VHL

      FamilyInfo: Case II/3 (the patient’s son) had retina angioma with renal carcinoma. Case II/2 (his other son) also had the mutation and presented with renal carcinoma, central nervous system haemangioblastoma, pheochromacytoma and pancreatic cysts. Case III/3 (his grandson; son of Case II/2) also had the mutation and was symptomatic but specific phenotypes were not specified. Pedigree: see Figure 2.

      CasePresentingHPOs: HP:0010797 (hemangioblastoma)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: R167W (8702C->T)

      ClinVar: 2218 https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: CA020450 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.499C%3ET

      gnomAD: 0.000007954 https://gnomad.broadinstitute.org/variant/3-10191506-C-T

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Italian DiseaseEntity:VHL DiseaseEntity:hemangioblastoma Mutation:Germline cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP ClinVarID:2218 CAID:CA020450 MutationType:missense_variant;transition CivicName:R167W(c.499C>T) FamilyPedigree ClinVarID:Yes Familial inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
    2. ClingenBaseline 27 Oct 2026
      In patient II/1 (Figure 1) the 8684 C->T substitution causing the nonsense R161X mutation in the putative protein was found

      PatientID: II/1

      KindredID: 1

      Case: F, 33Y0M, Italian

      DiseaseAssertion: VHL

      FamilyInfo: A patient was found to have a mutation in the VHL gene (R161* (c.481C>T)), this patients parents were tested for the same mutation in VHL, but testing revealed no VHL gene mutation. Pedigree: see Figure 1.

      CasePresentingHPOs: HP:0006880 (cerebellar hemangioblastoma)

      CaseHPOFreeText: developed cerebellar hemangioblastoma at age 33

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R161* (c.481C>T)

      LegacyVariant: R161X (8684C>T)

      ClinVar: 2217 https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: R161* (c.481C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:DeNovoAssertion Ethnicity:Italian DiseaseEntity:cerebellarhemangioblastoma DiseaseEntity:VHL AgeOfPresentation:cerebellarhemangioblastoma:33 Mutation:Germline cDNAposition:481 ProteinPosition:161 AminoAcidChange:ARGtoTER ClinVarID:2217 MutationType:stop_gained CivicName:R161*(c.481C>T) FamilyPedigree deNovoConfirmed ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    3. ClingenBaseline 26 Oct 2026
      One of his two children (III/3) also developed the disease.

      PatientID: III/3

      KindredID: 2

      Case: F, Age Unknown, Italian

      DiseaseAssertion: VHL

      FamilyInfo: Case II/3 (patient III/3's father) had retina angioma with renal carcinoma. Case II/2 (her uncle) also had the mutation and presented with renal carcinoma, central nervous system haemangioblastoma, pheochromacytoma and pancreatic cysts. Case I/1 (her grandfather) also had the mutation and presented with haemangioblastom. Pedigree: see Figure 2.

      CasePresentingHPOs: N/A

      CaseHPOFreeText: This patient has developed VHL disease as mentioned in the paper, however, specific clinical presentations of the disease are not outlined.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: R167W (8702C->T)

      ClinVar: 2218 https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: CA020450 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.499C%3ET

      gnomAD: 0.000007954 https://gnomad.broadinstitute.org/variant/3-10191506-C-T

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Italian DiseaseEntity:VHL Mutation:Germline cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP CAID:CA020450 MutationType:missense_variant;transition CivicName:R167W(c.499C>T) FamilyPedigree ClinVarID:2218 ClinVarID:Yes Familial inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
    4. ClingenBaseline 23 Oct 2026
      8702C->T substitution was detected in patient II/3

      PatientID: II/3

      KindredID: 2

      Case: M, Age Unknown, Italian

      DiseaseAssertion: VHL

      FamilyInfo: A patient was found to have a mutation in the VHL gene (R167W (c.499C>T)). The patient inherited this mutated gene from his father (I/1) who had haemangioblastoma. His brother (II/2) also manifested renal carcinoma, central nervous system haemangioblastoma, pheochromocytoma and pancreatic cysts. One of his two children (III/3) also developed the disease. Pedigree: see Figure 2.

      CasePresentingHPOs: HP:0009711, HP:0005584 (retinal capillary hemangioma, renal cell carcinoma)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant:R167W (8702C>T)

      ClinVar: 2218 https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: CA020450 (http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.499C%3ET)

      gnomAD: 0.000007954 https://gnomad.broadinstitute.org/variant/3-10191506-C-T

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Italian DiseaseEntity:VHL DiseaseEntity:renalcellcarcinoma DiseaseEntity:retinalcapillaryhemangioma Mutation:Germline cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP ClinVarID:2218 MutationType:missense_variant;transition FamilyPedigree CivicName:R167W(c.499C>T) CAID:CA020450 ClinVarID:Yes Familial inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC5954429/
  52. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Improved detection of germline mutations in the von Hippel-Lindau disease tumor suppressor gene
    5
    1. ClingenBaseline 29 Oct 2026

      GroupID: 152

      DiseaseAssertion: VHL

      GroupSize: N/A

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: N/A

      GroupAgeRange: N/A

      GroupInfo: VHL family found to have a germline rearrangement of the VHL gene. The number of family members included in this study is not specified.

      GroupPresentingHPOs: N/A

      GroupHPOFreeText: Patients within this family were found to have a clinical diagnosis of VHL disease, however, the presenting phenotypes were not specified.

      GroupNotHPOs: HP:0002666 (Pheochromocytoma)

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: c.712C>T

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL Mutation:Germline RefSeq:AF010238.1 cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP ClinVarID:2218 ClinVarID:Yes MutationType:missense_variant;transition CivicName:R167W(c.499C>T) Familial FamilyCohort inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 28 Oct 2026

      GroupID: 81

      DiseaseAssertion: VHL

      GroupSize: Unknown

      GroupNumberMales: Unknown

      GroupNumberFemales: Unknown

      GroupEthnicity: Unknown

      GroupAgeRange: Unknown

      GroupInfo: This family group had a history of clinically confirmed VHL disease. Members of this family were found to harbour the c.337C>T variant causing a p.Arg113* stopgain (noted in the paper as c.550C>T due to Latif reference transcript being used). It was noted that this family had no history of pheochromocytoma's.

      GroupPresentingHPOs: N/A

      GroupHPOFreeText: Patients within this family were found to have a clinical diagnosis of VHL disease, however, the presenting phenotypes were not specified.

      GroupNotHPOs: HP:0002666 (pheochromocytoma)

      GroupNotHPOFreeText: This family had no history of pheochromocytoma's.

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R113* (c.337C>T)

      LegacyVariant: p.R113* (c.550C>T)

      ClinVarID: 220414 https://www.ncbi.nlm.nih.gov/clinvar/variation/220414/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: R113* (c.337C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL Mutation:Germline RefSeq:AF010238.1 cDNAposition:337 ProteinPosition:113 AminoAcidChange:ARGtoTER ClinVarID:220414 ClinVarID:Yes MutationType:stop_gained CivicName:R113*(c.337C>T) FamilyCohort inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    3. ClingenBaseline 28 Oct 2026

      GroupID: 184

      DiseaseAssertion: VHL

      GroupSize: Unknown

      GroupNumberMales: Unknown

      GroupNumberFemales: Unknown

      GroupEthnicity: Unknown

      GroupAgeRange: Unknown

      GroupInfo: This family group had a history of clinically confirmed VHL disease. Members of this family were found to harbour the c.481C>T variant causing a Arg161* stop gain (noted in the paper as c.694C>T due to Latif reference transcript being used). It was noted that this family had no history of pheochromocytoma's.

      GroupPresentingHPOs: N/A

      GroupHPOFreeText: Patients within this family were found to have a clinical diagnosis of VHL disease, however, the presenting phenotypes were not specified.

      GroupNotHPOs: HP:0002666 (pheochromocytoma)

      GroupNotHPOFreeText: It was noted that this family had no history of pheochromocytoma's.

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R161* (c.481C>T)

      LegacyVariant: p.R161* (c.694C>T)

      ClinVarID: 2217 https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: R161* (c.481C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL Mutation:Germline RefSeq:AF010238.1 cDNAposition:481 ProteinPosition:161 AminoAcidChange:ARGtoTER ClinVarID:2217 ClinVarID:Yes MutationType:stop_gained CivicName:R161*(c.481C>T) FamilyCohort inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    4. ClingenBaseline 28 Oct 2026

      GroupID: 69

      DiseaseAssertion: VHL

      GroupSize: N/A

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: N/A

      GroupAgeRange: N/A

      GroupInfo: VHL family found to have a germline rearrangement of the VHL gene. The number of family members included in this study is not specified.

      GroupPresentingHPOs: N/A

      GroupHPOFreeText: Patients within this family were found to have a clinical diagnosis of VHL disease, however, the presenting phenotypes were not specified.

      GroupNotHPOs: HP:0002666 (Pheochromocytoma)

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.C162F (c.485G>T)

      LegacyVariant: c.698G>T

      CaseProblemVariantFreeText: N/A

      ClinVarID: 43604, https://www.ncbi.nlm.nih.gov/clinvar/variation/43604/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: C162F (c.485G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL Mutation:Germline RefSeq:AF010238.1 cDNAposition:485 ProteinPosition:162 AminoAcidChange:CYStoPHE ClinVarID:43604 ClinVarID:Yes MutationType:missense_variant;transversion CivicName:C162F(c.485G>T) Familial FamilyCohort inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    5. ClingenBaseline 27 Oct 2026

      GroupID: 78

      DiseaseAssertion: VHL

      GroupSize: N/A

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: N/A

      GroupAgeRange: N/A

      GroupInfo: VHL family found to have a germline rearrangement of the VHL gene. The number of family members included in this study is not specified.

      GroupPresentingHPOs: N/A

      GroupHPOFreeText: Patients within this family were found to have a clinical diagnosis of VHL disease, however, the presenting phenotypes were not specified.

      GroupNotHPOs: HP:0002666 (Pheochromocytoma)

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.E186* (c.556G>T)

      LegacyVariant: c.769G>T

      CaseProblemVariantFreeText: N/A

      ClinVarID: 381602, https://www.ncbi.nlm.nih.gov/clinvar/variation/381602/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: E186* (c.556G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL Mutation:Germline RefSeq:AF010238.1 cDNAposition:556 ProteinPosition:186 AminoAcidChange:GLUtoTER ClinVarID:381602 ClinVarID:Yes MutationType:missense_variant;transversion CivicName:E186*(c.556G>T) Familial FamilyCohort inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/9829911/
  53. www-sciencedirect-com.uhn.idm.oclc.org www-sciencedirect-com.uhn.idm.oclc.org
    Endolymphatic sac tumor (aggressive papillary tumor of middle ear and temporal bone): Report of two cases with analysis of the VHL gene
    1
    1. ClingenBaseline 29 Oct 2026
      Family historyThe family medical history disclosed the presence of symptoms of VHLD in the patient's grandfather, uncle, and father. In particular, the patient's father presented with multi-tumor syndrome and evidence of genetic VHLD due to causal mutation in VHL gene in exon 1 TCG(Ser65)→TTG(Leu). At the age of 30, he was operated on for cerebellar hemangioblastoma, and died of disseminated bilateral renal cell carcinoma of kidneys with multi-organ distant metastases 13 years later at the age of 43.

      PatientID: N/A (father)

      KindredID: 1

      Case: M, 43Y0M (deceased), Ethnicity Unknown

      DiseaseAssertion: assumed VHL

      FamilyInfo: The family medical history disclosed the presence of symptoms of VHLD in the patient’s daughter, brother, and father. His daughter was detected with the c.194C>T mutation in two of her tumors, likely germline with the familial relations. She also had undergone brain surgery at 23Y due to a cerebellar hemangioblastoma, and an ELST

      CasePresentingHPOs: HP:0006880; HP:0005584 (cerebellar hemangioblastoma; Renal cell carcinoma)

      CaseHPOFreeText: At the age of 30, he was operated on for cerebellar hemangioblastoma, and died of disseminated bilateral renal cell carcinoma of kidneys with multi-organ distant metastases 13 years later at the age of 43.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.S65L (c.194C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 182975, https://www.ncbi.nlm.nih.gov/clinvar/variation/182975/

      CAID: N/A

      gnomAD: https://gnomad.broadinstitute.org/variant/3-10183725-C-T

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: S65L (c.194C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:cerebellarhemangioblastoma DiseaseEntity:renalcellcarcinoma ProteinPosition:65 CivicName:S65L(c.194C>T) cDNAposition:194 AminoAcidChange:SERtoLEU MutationType:missense_variant;transition ClinVarID:182975 ClinVarID:Yes Familial RefSeq:AF010238.1 Mutation:Germline inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    www-sciencedirect-com.uhn.idm.oclc.org/science/article/pii/S0344033808000484
  54. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Identification and In Silico Analysis of Novel von Hippel-Lindau (VHL) Gene Variants from a Large Population
    2
    1. ClingenBaseline 29 Oct 2026

      PatientID: 6

      KindredID: 6

      Case: Sex Unknown, 27Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: Family history noted but details not specified.

      CasePresentingHPOs: HP:0002666; HP:0010797; HP:0009711 (Pheochromocytoma, Hemangioblastoma, Retinal capillary hemangioma)

      CaseHPOFreeText: CNS and retinal capillary hemangioblastoma, pheochromocytoma.

      CaseNotHPOs: HP:0006770; HP:0000107; HP:0001732 (Clear cell renal cell carcinoma, Renal cyst, Abnormality of the pancreas)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: Table S1, S2 and S3

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:hemangioblastoma DiseaseEntity:retinalcapillaryhemangioma Mutation:Germline RefSeq:NM_000551.3 cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP ClinVarID:2218 ClinVarID:Yes MutationType:missense_variant;transition CivicName:R167W(c.499C>T) NoFamilyInfo Familial SupplementalData ExperimentalAssay DiseaseEntity:pheochromocytoma inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 26 Oct 2026

      PatientID: 218

      KindredID: 218

      Case: Sex Unknown, 17Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: Positive VHL family history.

      CasePresentingHPOs: HP:0010797 (hemangioblastoma )

      CaseHPOFreeText: N/A

      CaseNotHPOs: HP:0009711, HP:0001737, HP:0002666, HP:0000107, HP:0006770 (retinal capillary hemangioma, pancreatic cyst, pheochromocytoma, renal cyst, clear cell renal cell carcinoma)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: Table S1, S2, S3.

      Variant: p.R161* (c.481C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2217 https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

      CAID: CA020408 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.481C%3ET

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: R161*(c.481C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:pheochromocytoma DiseaseEntity:VHL RefSeq:NM_000551.3 Mutation:Germline MutationType:stop_gained ClinVarID:2217 ProteinPosition:161 CivicName:R161*(c.481C>T) cDNAposition:481 CAID:CA020408 Familial SupplementalData ClinVarID:Yes AminoAcidChange:ARGtoTER ExperimentalAssay inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/21463266/
  55. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Solitary juxtapapillary capillary retinal angioma and von Hippel-Lindau disease
    1
    1. ClingenBaseline 29 Oct 2026

      PatientID: 5

      KindredID: 1

      Case: Sex Unknown, 15Y10M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: None.

      CasePresentingHPOs: HP:0009711 (retinal capillary hemangioma)

      CaseHPOFreeText: At first presentation (age 14Y3M) the patient had a visual acuity of 20/200. The angioma showed an exophytic growth pattern and was located in the inferior disc margin.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: Medical screening for other VHL lesions comprised magnetic resonance imaging (MRI) of the brain and spinal cord (gadolinium-enhanced), urine catecholamines, and abdominal sonography or computed tomography (CT). No VHL lesions present other than the retinal angioma reported.

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.Q164H (c.492G>T)

      LegacyVariant: p.Q164H (c.705G>T)

      CaseProblemVariantFreeText: N/A

      ClinVarID: 456566 https://www.ncbi.nlm.nih.gov/clinvar/variation/456566/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: Q164H (c.492G>T)

      MultipleGeneVariants: N/A

      MutationType:missense_variant;transversion DiseaseEntity:VHL NonFamilial DiseaseEntity:retinalcapillaryhemangioma AgeOfPresentation:RetinalCapillaryHemangioma:14 Mutation:Germline AssumedRefSeq:AF010238.1 cDNAposition:492 ProteinPosition:164 AminoAcidChange:GLNtoHIS ClinVarID:456566 ClinVarID:Yes CivicName:Q164H(c.492G>T) InheritancePattern:AutosomalDominant inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/17392848/
  56. onlinelibrary.wiley.com onlinelibrary.wiley.com
    Characterization of endolymphatic sac tumors and von Hippel–Lindau disease in the International Endolymphatic Sac Tumor Registry
    1
    1. ClingenBaseline 29 Oct 2026
      1 France c.256C>T p.Pro86Ser

      GroupID: 6

      Case: Sex unknown, Age unknown, French

      DiseaseAssertion: VHL

      FamilyInfo: Unknown. 1 registrant was found with this variant; no family info was mentioned

      CasePresentingHPOs: HP:0030393 (Endolymphatic sac tumor)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.P86S (c.256C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 178692 https://www.ncbi.nlm.nih.gov/clinvar/variation/178692/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transition

      CivicName: P86S (c.256C>T)

      MultipleGeneVariants: N/A

      ClinVarID:178692 ClinVarID:Yes Mutation:Germline DiseaseEntity:endolymphaticsactumor DiseaseEntity:VHL RefSeq:NM_000551.3 ProteinPosition:86 CivicName:P86S(c.256C>T) cDNAposition:256 AminoAcidChange:PROtoSER MutationType:missense_variant;transition Ethnicity:French inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    onlinelibrary.wiley.com/doi/full/10.1002/hed.24067
  57. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Pathogenicity of DNA Variants and Double Mutations in Multiple Endocrine Neoplasia Type 2 and Von Hippel-Lindau Syndrome
    2
    1. ClingenBaseline 29 Oct 2026
      A 50-yr-old male (II.1) presenting with hemangioblastomas of the central nervous system was found to have a hemizygous VHL c.241 C→T (p.Pro81Ser) variant and a concomitant large deletion encompassing all exons of the VHL gene. The screening of his relatives confirmed that the p.Pro81Ser has been inherited from his healthy father (I.1), whereas the large deletion occurred de novo. The proband’s son (III.1) inherited his father’s germline VHL large deletion, and not the VHL p. Pro81Ser variant. In addition, the son (III.1) was found to have a hemizygous VHL c.340 + 5 G→C (IVS1 + 5) polymorphic variant, present on the allele inherited from his healthy mother (II.2). The son (III.1) was, therefore, clinically screened and found to have retinal and cerebellar hemangioblastomas as well as pancreatic cysts, typical lesions of VHL demonstrating that VHL cosegregated with, and is therefore caused by, the VHL large deletion and not the p.Pro81Ser variant.These case reports were, therefore, instrumental in raising two issues. First, could the long-presumed pathogenic RET and VHL mutations actually be harmless polymorphisms? Second, if the RET and VHL variants are pathogenic, then how commonly do patients with heritable PGL harbor two or more pathogenic mutations in the same or different genes?

      PatientID: II.1

      KindredID: 3

      Case: M, 50Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: He inherited the p.Pro81Ser mutation from his healthy father (I.1) and the other mutation occured de novo. The patient had a son (III.1) who inherited his germline VHL large deletion, but not the VHL p. Pro81Ser variant. The son also had another VHL mutation which he inherited from his healthy mother (II.2). The son presented with retinal and cerebellar hemangioblastomas as well as pancreatic cysts. Refer to figure 1, pedigree C for family information.

      CohortInfo: Patients were registrants from the European-American Pheochromocytoma-Paraganglioma and German von Hippel-Lindau Disease Registries.

      CasePresentingHPOs: HP:0010797, HP:0001737 (hemangioblastoma, pancreatic cysts)

      CaseHPOFreeText: Presented with hemangioblastoma at age 50.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: RET/SDHB/SDHD/SDHC

      PreviouslyPublished: May have been previously published in 11106358 and/or 7563486.

      SupplementalData: Yes, File 1 for methods.

      Variant: p.P81S(c.241C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2233 https://www.ncbi.nlm.nih.gov/clinvar/variation/2233/

      CAID: N/A

      gnomAD: 0.0002179 https://gnomad.broadinstitute.org/variant/3-10183772-C-T

      VariantEvidence: The patient was hemizygous for this mutation.

      MutationType: missense_variant;transition

      CivicName: Exon 1-3 Deletion and P81S (c.241C>T)

      MultipleGeneVariants: Germline, VHL, Exon 1-3 deletion

      MutationType:missense_variant;transition InheritancePattern:AutosomalDominant Mutation:Germline DiseaseEntity:VHL Familial FamilyPedigree SupplementalData RefSeq:NM_000551.3 MultipleVHLVariants DiseaseEntity:hemangioblastoma AgeOfPresentation:hemangioblastoma:50 DiseaseEntity:pancreaticcysts PreviousTesting:RET/SDHB/SDHD/SDHC ProteinPosition:81 AminoAcidChange:PROtoSER CivicName:P81S(c.241C>T) cDNAposition:241 ClinVarID:2233 ClinVarID:Yes ExperimentalAssay CivicName:Exon1-3DeletionandP81S(c.241C>T) inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 24 Oct 2026
      p.Pro81Ser has been inherited from his healthy father (I.1)

      PatientID: I.1

      KindredID: 3

      Case: M, Age Unknown, Ethnicity Unknown

      DiseaseAssertion:Asymptomatic

      FamilyInfo: The patient had a son who he passed this mutation to. The son (II.1) presented with hemangioblastoma and pancreatic cysts and had an additional de novo exon 1-3 deletion. Refer to figure 1, pedigree C for family information.

      CohortInfo: Patients were registrants from the European-American Pheochromocytoma-Paraganglioma and German von Hippel-Lindau Disease Registries.

      CasePresentingHPOs: N/A

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: RET/SDHB/SDHD/SDHC

      PreviouslyPublished: May have been previously published in 11106358 and/or 7563486.

      SupplementalData: Yes, File 1 for methods.

      Variant: p.P81S(c.241C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2233 https://www.ncbi.nlm.nih.gov/clinvar/variation/2233/

      CAID: N/A

      gnomAD: 0.0002179 https://gnomad.broadinstitute.org/variant/3-10183772-C-T

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: P81S(c.241C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:asymptomatic Familial FamilyPedigree PreviousTesting:RET/SDHB/SDHD/SDHC ProteinPosition:81 CivicName:P81S(c.241C>T) cDNAposition:241 AminoAcidChange:PROtoSER ClinVarID:2233 ClinVarID:Yes SupplementalData RefSeq:NM_000551.3 MutationType:missense_variant;transition Mutation:Germline ExperimentalAssay inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC2805484/
  58. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Germline VHL gene mutations in three Serbian families with von Hippel-Lindau disease
    1
    1. ClingenBaseline 29 Oct 2026
      family A, a c.490G>T/ p.Gly93Cys

      PatientID: AII2

      KindredID: A

      Case: F, 33Y0M, Serbian

      DiseaseAssertion: VHL

      FamilyInfo: Families were selected based on their clinical data and family history. Patient’s mother (AI1) had CNS hemangioblastoma. The patient’s son (AIII3) had severe arterial hypertension since 12Y0M and left pheochromocytoma was found and removed at 24Y0M. The patient’s sister (AII2) has pheochromocytoma and CNS hemangioblastoma. Genetic testing was performed on nine family members and two carried the heterozygous missense variant - current patient and her son. The patient’s mother and sister with VHL were not genetically tested. See pedigree in figure 1.

      CasePresentingHPOs: HP:0002666 (pheochromocytoma)

      CaseHPOFreeText: Patient was diagnosed with pheochromocytoma at 33Y0M.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.G93C (c.277G>T)

      LegacyVariant: p.G93C (c.490G>T)

      CaseProblemVariantFreeText: N/A

      ClinVarID: 223175, https://www.ncbi.nlm.nih.gov/clinvar/variation/223175/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense variant; transversion

      CivicName: G93C (c.277G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline MutationType:missense_variant;transversion DiseaseEntity:VHL DiseaseEntity:pheochromocytoma AgeOfPresentation:pheochromocytoma:33 CivicName:G93C(c.277G>T) cDNAPosition:277 ProteinPosition:93 AminoAcidChange:GLYtoCYS ClinVarID:Yes ClinVarID:223175 FamilyPedigree Familial AssumedRefSeq:AF010238.1 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/17688370/
  59. academic.oup.com academic.oup.com
    Hemangioblastomas of Central Nervous System: Molecular Genetic Analysis and Clinical Management
    2
    1. ClingenBaseline 29 Oct 2026
      In Patient 1, who was 40 years old and had a cerebellar hemangioblastoma, the P86L missense heterozygous germline mutation was identified in exon 1. The DNA analysis of close relatives did not show affected subjects. This patient was recommended for VHL disease surveillance protocols (15) (Table 4) and developed a retinal hemangioblastoma 4 years after diagnosis. TABLE 4.von Hippel-Lindau protocol for periodical clinical monitoring (7) Open in new tab

      PatientID: 1

      KindredID: 1

      Case: M, 40Y0M, Italian

      DiseaseAssertion: VHL

      FamilyInfo: None - The DNA analysis of close relatives did not show affected subjects

      CasePresentingHPOs: HP:0006880; HP:0009711 (cerebellar hemangioblastoma; retinal capillary hemangioblastoma)

      CaseHPOFreeText: also had high intercranial pressure; developed a retinal hemangioblastoma 4 years after diagnosis (diagnosis at 32Y0M; rHAB at 36Y0M)

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.P86L (c.257C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 182977 https://www.ncbi.nlm.nih.gov/clinvar/variation/182977/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: P86L (c.257C>T)

      MultipleGeneVariants: N/A

      Ethnicity:Italian DiseaseEntity:cerebellarhemangioblastoma DiseaseEntity:retinalcapillaryhemangioma AgeOfPresentation:cerebellarhemangioblastoma:32 DiseaseEntity:VHL AgeOfPresentation:retinalcapillaryhemangioma:36 ProteinPosition:86 CivicName:P86L(c.257C>T) cDNAposition:257 AminoAcidChange:PROtoLEU MutationType:missense_variant;transition ClinVarID:182977 ClinVarID:Yes Mutation:Germline AssumedRefSeq:NM_000551.3 NonFamilial inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 28 Oct 2026
      At VHL gene analysis of close relatives, R167W was detected in her sister as well, who was negative at clinical and instrumental screening.

      PatientID: None (sister of Patient 9)

      KindredID: 2

      Case: F, age unknown, Italian

      DiseaseAssertion: asymptomatic

      FamilyInfo: R167W was detected in her sister as well, who had cerebellar hemangioblastoma.

      CasePresentingHPOs: None

      CaseHPOFreeText: negative at clinical and instrumental screening

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 2218 https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954 https://gnomad.broadinstitute.org/variant/3-10191506-C-T

      VariantEvidence: N/A

      MutationType: missense_variant; transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      Mutation:Germline Ethnicity:Italian DiseaseEntity:asymptomatic InheritancePattern:AutosomalDominant AssumedRefSeq:NM_000551.3 CivicName:R167W(c.499C>T) cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP MutationType:missense_variant;transition ClinVarID:2218 ClinVarID:Yes Familial inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    academic.oup.com/neurosurgery/article-abstract/56/6/1215/2744028
  60. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Molecular genetic diagnosis of von Hippel-Lindau disease in familial phaeochromocytoma.
    1
    1. ClingenBaseline 29 Oct 2026
      V155L

      PatientID: None

      KindredID: A

      Case: M, 11Y0M, Welsh

      DiseaseAssertion: Pheochromocytoma

      FamilyInfo: The patient had a sister that presented with bilateral pheochromocytoma at 17Y. The patient also had an asymptomatic parent.

      CasePresentingHPOs: HP:0002666 (Pheochromocytoma)

      CaseHPOFreeText: The patient presented with bilateral pheochromocytoma at 11Y.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: RET

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.V84L(c.250G>T)

      LegacyVariant: p.V155L(c.463G>T)

      CaseProblemVariantFreeText: bandshift in exon 1 and genomic sequencing indicated a G>T transversion at nucleotide 463, substituting a valine for leucine at codon 155 (V155L). Leading to NM_000551.3:p.V84L(c.250G>T)

      ClinVarID: 2236, http://www.ncbi.nlm.nih.gov/clinvar/variation/2236

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: V84L(c.250G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Welsh DiseaseEntity:pheochromocytoma AgeOfPresentation:pheochromocytoma:11 Mutation:Germline RefSeq:N/A AssumedRefSeq:AF010238.1 cDNAposition:250 ProteinPosition:84 AminoAcidChange:VALtoLEU ClinVarID:Yes ClinVarID:2236 MutationType:missense_variant;transversion CivicName:V84L(c.250G>T) PreviousTesting:RET FamilyPedigree Familial inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC1051741/
  61. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Von Hippel-Lindau disease in a Newfoundland kindred.
    8
    1. ClingenBaseline 29 Oct 2026
      recognized in a large family that originated in Newfoundland but has some members who live in New Brunswick and Ontario. A collaborative investigation was begun in 1982 to document the number of affected members and the extent of their disease and to improve management of the disease. The condition has been documented in 38 members of the family, 28 living and 10 dead. The most common manifestations are retinal angioma (present in 60% of the gene carriers) and pheochromocytoma (present in 53%). Of the 28 living affected members 14 had been identified before the study began. Only 3 of the 14 patients in whom the disease was subsequently diagnosed presented with symptoms; in the remaining 11 the condition was detected by routine screening. Overall the mean age at the time of diagnosis was 23 years; in the 21 affected members of the fourth generation it was 18 years.

      PatientID: II-5

      KindredID: 1

      Case: M, Age Unknown (deceased), Ethnicity Unknown

      DiseaseAssertion: Assumed VHL

      FamilyInfo: 38 family members had been affected at the date of 1986, and 10 had passed away. Pheochromocytoma, cerebellar, spinal and retinal hemangioblastomas, and various cysts were clinical manifestations of VHL seen throughout the family. This male (II-5) appears to have inherited this disease from his father, and passed it onto his son. See Fig. 1 for family pedigree.

      CasePresentingHPOs: HP:0002666 (pheochromocytoma)

      CaseHPOFreeText: Patient had pheochromocytoma described as “probable”. No further details were provided.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: Although never given at the time of this publication, the germline mutation is confirmed in this family in later publications (PMID 7987306; 29437867) for this specific family. It is only assumed this member had the VHL mutation.

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:pheochromocytoma Mutation:Germline RefSeq:N/A CivicName:R167W(c.499C>T) cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP MutationType:missense_variant;transition Familial FamilyPedigree ClinVarID:2218 ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 28 Oct 2026
      recognized in a large family that originated in Newfoundland but has some members who live in New Brunswick and Ontario. A collaborative investigation was begun in 1982 to document the number of affected members and the extent of their disease and to improve management of the disease. The condition has been documented in 38 members of the family, 28 living and 10 dead. The most common manifestations are retinal angioma (present in 60% of the gene carriers) and pheochromocytoma (present in 53%). Of the 28 living affected members 14 had been identified before the study began. Only 3 of the 14 patients in whom the disease was subsequently diagnosed presented with symptoms; in the remaining 11 the condition was detected by routine screening. Overall the mean age at the time of diagnosis was 23 years; in the 21 affected members of the fourth generation it was 18 years.

      PatientID: III-8

      KindredID: 1

      Case: M, Age Unknown, Ethnicity Unknown

      DiseaseAssertion: Assumed VHL

      FamilyInfo: 38 family members had been affected at the date of 1986, and 10 had passed away. Pheochromocytoma, cerebellar, spinal and retinal hemangioblastomas, and various cysts were clinical manifestations of VHL seen throughout the family. This male (III-8) appears to have inherited this disease from his father and has passed it onto to his kin thereafter. See Fig. 1 for family pedigree.

      CasePresentingHPOs: HP:0002666 (pheochromocytoma)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: Although never given at the time of this publication, the germline mutation is confirmed in this family in later publications (PMID 7987306; 29437867) for this specific family. It is only here assumed this member had the VHL mutation.

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline RefSeq:N/A cDNAposition:499 CivicName:R167W(c.499C>T) ProteinPosition:167 AminoAcidChange:ARGtoTRP MutationType:missense_variant;transition ClinVarID:2218 ClinVarID:Yes Familial FamilyPedigree DiseaseEntity:pheochromocytoma inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    3. ClingenBaseline 28 Oct 2026
      recognized in a large family that originated in Newfoundland but has some members who live in New Brunswick and Ontario. A collaborative investigation was begun in 1982 to document the number of affected members and the extent of their disease and to improve management of the disease. The condition has been documented in 38 members of the family, 28 living and 10 dead. The most common manifestations are retinal angioma (present in 60% of the gene carriers) and pheochromocytoma (present in 53%). Of the 28 living affected members 14 had been identified before the study began. Only 3 of the 14 patients in whom the disease was subsequently diagnosed presented with symptoms; in the remaining 11 the condition was detected by routine screening. Overall the mean age at the time of diagnosis was 23 years; in the 21 affected members of the fourth generation it was 18 years.

      PatientID: IV-35

      KindredID: 1

      Case: M, Age Unknown, Ethnicity Unknown

      DiseaseAssertion: Assumed VHL

      FamilyInfo: 38 family members had been affected at the date of 1986, and 10 had passed away. Pheochromocytoma, cerebellar, spinal and retinal hemangioblastomas, and various cysts were clinical manifestations of VHL seen throughout the family. This patient (IV-35) appears to have inherited this disease from his mother, along with many of his siblings. See Fig. 1 for family pedigree.

      CasePresentingHPOs: HP:0002666 (pheochromocytoma)

      CaseHPOFreeText: This member had pheochromocytoma which was not further described.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: Although never given at the time of this publication, the germline mutation is confirmed in this family in later publications (PMID 7987306; 29437867) for this specific family. It is only here assumed this member had the VHL mutation.

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline RefSeq:N/A DiseaseEntity:pheochromocytoma CivicName:R167W(c.499C>T) cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP MutationType:missense_variant;transition Familial FamilyPedigree ClinVarID:2218 ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    4. ClingenBaseline 28 Oct 2026
      recognized in a large family that originated in Newfoundland but has some members who live in New Brunswick and Ontario. A collaborative investigation was begun in 1982 to document the number of affected members and the extent of their disease and to improve management of the disease. The condition has been documented in 38 members of the family, 28 living and 10 dead. The most common manifestations are retinal angioma (present in 60% of the gene carriers) and pheochromocytoma (present in 53%). Of the 28 living affected members 14 had been identified before the study began. Only 3 of the 14 patients in whom the disease was subsequently diagnosed presented with symptoms; in the remaining 11 the condition was detected by routine screening. Overall the mean age at the time of diagnosis was 23 years; in the 21 affected members of the fourth generation it was 18 years.

      PatientID: IV-5

      KindredID: 1

      Case: M, Age Unknown, Ethnicity Unknown

      DiseaseAssertion: Assumed VHL

      FamilyInfo: 38 family members had been affected at the date of 1986, and 10 had passed away. Pheochromocytoma, cerebellar, spinal and retinal hemangioblastomas, and various cysts were clinical manifestations of VHL seen throughout the family. This patient (IV-5) appears to have inherited this disease from his father, along with many of his siblings. See Fig. 1 for family pedigree.

      CasePresentingHPOs: HP:0002666 (pheochromocytoma)

      CaseHPOFreeText: This member had pheochromocytoma which was not further described.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: Although never given at the time of this publication, the germline mutation is confirmed in this family in later publications (PMID 7987306; 29437867) for this specific family. It is only here assumed this member had the VHL mutation.

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline RefSeq:N/A DiseaseEntity:pheochromocytoma CivicName:R167W(c.499C>T) cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP MutationType:missense_variant;transition Familial FamilyPedigree ClinVarID:2218 ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    5. ClingenBaseline 27 Oct 2026
      recognized in a large family that originated in Newfoundland but has some members who live in New Brunswick and Ontario. A collaborative investigation was begun in 1982 to document the number of affected members and the extent of their disease and to improve management of the disease. The condition has been documented in 38 members of the family, 28 living and 10 dead. The most common manifestations are retinal angioma (present in 60% of the gene carriers) and pheochromocytoma (present in 53%). Of the 28 living affected members 14 had been identified before the study began. Only 3 of the 14 patients in whom the disease was subsequently diagnosed presented with symptoms; in the remaining 11 the condition was detected by routine screening. Overall the mean age at the time of diagnosis was 23 years; in the 21 affected members of the fourth generation it was 18 years.

      PatientID: IV-12

      KindredID: 1

      Case: M, Age Unknown, Ethnicity Unknown

      DiseaseAssertion: Assumed VHL

      FamilyInfo: 38 family members had been affected at the date of 1986, and 10 had passed away. Pheochromocytoma, cerebellar, spinal and retinal hemangioblastomas, and various cysts were clinical manifestations of VHL seen throughout the family. This male (IV-12) appears to have inherited this disease from his mother however her children were unaffected at the time. See Fig. 1 for family pedigree.

      CasePresentingHPOs: HP:0009711 (retinal capillary hemangioma)

      CaseHPOFreeText: This member was examined in St. Johns at the Memorial University of Newfoundland. He had retinal angiomas which were not further described.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: Although never given at the time of this publication, the germline mutation is confirmed in this family in later publications (PMID 7987306; 29437867) for this specific family. It is only here assumed this member had the VHL mutation.

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline RefSeq:N/A DiseaseEntity:retinalcapillaryhemangioma cDNAposition:499 CivicName:R167W(c.499C>T) ProteinPosition:167 ClinVarID:2218 MutationType:missense_variant;transition ClinVarID:Yes Familial FamilyPedigree AminoAcidChange:ARGtoTRP inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    6. ClingenBaseline 27 Oct 2026
      recognized in a large family that originated in Newfoundland but has some members who live in New Brunswick and Ontario. A collaborative investigation was begun in 1982 to document the number of affected members and the extent of their disease and to improve management of the disease. The condition has been documented in 38 members of the family, 28 living and 10 dead. The most common manifestations are retinal angioma (present in 60% of the gene carriers) and pheochromocytoma (present in 53%). Of the 28 living affected members 14 had been identified before the study began. Only 3 of the 14 patients in whom the disease was subsequently diagnosed presented with symptoms; in the remaining 11 the condition was detected by routine screening. Overall the mean age at the time of diagnosis was 23 years; in the 21 affected members of the fourth generation it was 18 years.

      PatientID: IV-21

      KindredID: 1

      Case: F, Age Unknown, Ethnicity Unknown

      DiseaseAssertion: Assumed VHL

      FamilyInfo: 38 family members had been affected at the date of 1986, and 10 had passed away. Pheochromocytoma, cerebellar, spinal and retinal hemangioblastomas, and various cysts were clinical manifestations of VHL seen throughout the family. This patient (IV-21) appears to have inherited this disease from her mother. See Fig. 1 for family pedigree.

      CasePresentingHPOs: HP:0009711 (retinal capillary hemangioma)

      CaseHPOFreeText: This member was examined in St. Johns at the Memorial University of Newfoundland. She had retinal angiomas which were not further described.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: Although never given at the time of this publication, the germline mutation is confirmed in this family in later publications (PMID 7987306; 29437867) for this specific family. It is only here assumed this member had the VHL mutation.

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline RefSeq:N/A DiseaseEntity:retinalcapillaryhemangioma cDNAposition:499 CivicName:R167W(c.499C>T) ProteinPosition:167 AminoAcidChange:ARGtoTRP MutationType:missense_variant;transition ClinVarID:2218 ClinVarID:Yes Familial FamilyPedigree inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    7. ClingenBaseline 27 Oct 2026
      recognized in a large family that originated in Newfoundland but has some members who live in New Brunswick and Ontario. A collaborative investigation was begun in 1982 to document the number of affected members and the extent of their disease and to improve management of the disease. The condition has been documented in 38 members of the family, 28 living and 10 dead. The most common manifestations are retinal angioma (present in 60% of the gene carriers) and pheochromocytoma (present in 53%). Of the 28 living affected members 14 had been identified before the study began. Only 3 of the 14 patients in whom the disease was subsequently diagnosed presented with symptoms; in the remaining 11 the condition was detected by routine screening. Overall the mean age at the time of diagnosis was 23 years; in the 21 affected members of the fourth generation it was 18 years.

      PatientID: III-7

      KindredID: 1

      Case: M, Age Unknown (deceased), Ethnicity Unknown

      DiseaseAssertion: Assumed VHL

      FamilyInfo: 38 family members had been affected at the date of 1986, and 10 had passed away. Pheochromocytoma, cerebellar, spinal and retinal hemangioblastomas, and various cysts were clinical manifestations of VHL seen throughout the family. This male (III-7) appears to have inherited this disease from his father and has passed it onto to his kin thereafter. See Fig. 1 for family pedigree.

      CasePresentingHPOs: HP:0002666 (pheochromocytoma)

      CaseHPOFreeText: This patient had pheochromocytoma as well as Vitamin-D-Resistant rickets, likely inherited from his mother.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: Although never given at the time of this publication, the germline mutation is confirmed in this family in later publications (PMID 7987306; 29437867) for this specific family. It is only here assumed this member had the VHL mutation.

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline RefSeq:N/A CivicName:R167W(c.499C>T) cDNAposition:499 ProteinPosition:167 MutationType:missense_variant;transition AminoAcidChange:ARGtoTRP ClinVarID:2218 ClinVarID:Yes Familial FamilyPedigree DiseaseEntity:pheochromocytoma inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    8. ClingenBaseline 27 Oct 2026
      recognized in a large family that originated in Newfoundland but has some members who live in New Brunswick and Ontario. A collaborative investigation was begun in 1982 to document the number of affected members and the extent of their disease and to improve management of the disease. The condition has been documented in 38 members of the family, 28 living and 10 dead. The most common manifestations are retinal angioma (present in 60% of the gene carriers) and pheochromocytoma (present in 53%). Of the 28 living affected members 14 had been identified before the study began. Only 3 of the 14 patients in whom the disease was subsequently diagnosed presented with symptoms; in the remaining 11 the condition was detected by routine screening. Overall the mean age at the time of diagnosis was 23 years; in the 21 affected members of the fourth generation it was 18 years.

      PatientID: IV-2

      KindredID: 1

      Case: F, Age Unknown, Ethnicity Unknown

      DiseaseAssertion: Assumed VHL

      FamilyInfo: 38 family members had been affected at the date of 1986, and 10 had passed away. Pheochromocytoma, cerebellar, spinal and retinal hemangioblastomas, and various cysts were clinical manifestations of VHL seen throughout the family. This patient (IV-2) appears to have inherited this disease from her father, along with many of her siblings. She also had an affected daughter with retinal angiomas. See Fig. 1 for family pedigree.

      CasePresentingHPOs: HP:0009711 (retinal capillary hemangioma)

      CaseHPOFreeText: This member had retinal angiomas which was not further described.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: Although never given at the time of this publication, the germline mutation is confirmed in this family in later publications (PMID 7987306; 29437867) for this specific family. It is only here assumed this member had the VHL mutation.

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline RefSeq:N/A DiseaseEntity:retinalcapillaryhemangioma cDNAposition:499 CivicName:R167W(c.499C>T) ProteinPosition:167 AminoAcidChange:ARGtoTRP MutationType:missense_variant;transition ClinVarID:2218 ClinVarID:Yes Familial FamilyPedigree inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC1490656/
  62. jmg.bmj.com jmg.bmj.com
    Germline mutations in the von Hippel-Lindau (VHL) gene in patients from Poland: disease presentation in patients with deletions of the entire VHL gene
    2
    1. ClingenBaseline 29 Oct 2026
      233A>T

      GroupID/ KindredID: 10

      DiseaseAssertion: VHL

      GroupSize: 4

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: Polish

      GroupAgeRange: N/A

      GroupInfo: Familial VHL stated; 4 family members recorded with this mutation.

      GroupPresentingHPOs: HP:0009711; HP:0010797; HP:0005584 (retinal capillary hemangioma, hemangioblastoma; renal cell carcinoma)

      GroupHPOFreeText: 4 patients were tallied with a retinal capillary hemangiomas, 3 with cHemangioblastomas, and 1 with RCC. These phenotypes couldn’t be paired as it was not clear.

      GroupNotHPOs: N/A

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.N78I (c.233A>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 223169 https://www.ncbi.nlm.nih.gov/clinvar/variation/223169/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transversion

      CivicName: N78I (c.233A>T)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:hemangioblastoma DiseaseEntity:renalcellcarcinoma Ethnicity:Polish Mutation:Germline AssumedRefSeq:NM_000551.3 ProteinPosition:78 CivicName:N78I(c.233A>T) cDNAposition:233 AminoAcidChange:ASNtoILE MutationType:missense_variant;transversion ClinVarID:223169 ClinVarID:Yes Familial FamilyCohort ExperimentalAssay inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 28 Oct 2026
      481C>T

      GroupID/ KindredID: 15

      Case: Age unknown, Sex unknown, Polish

      DiseaseAssertion: VHL

      FamilyInfo: This mutation (p.R161* (c.481C>T)) was found in Family No. 15 with 1 member affected.

      CasePresentingHPOs: HP:0009711; HP:0010797; HP:0005584 (retinal capillary hemangioma, hemangioblastoma, renal cell carcinoma)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R161* (c.481C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 2217 https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: R161* (c.481C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:hemangioblastoma DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:renalcellcarcinoma Ethnicity:Polish Mutation:Germline AssumedRefSeq:NM_000551.3 Familial ClinVarID:2217 ClinVarID:Yes MutationType:stop_gained ProteinPosition:161 cDNAposition:481 CivicName:R161*(c.481C>T) AminoAcidChange:ARGtoTER ExperimentalAssay inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    jmg.bmj.com/content/39/7/e38
  63. onlinelibrary.wiley.com onlinelibrary.wiley.com
    Retinal haemangioblastomas in von Hippel-Lindau germline mutation carriers: progression, complications and treatment outcome
    1
    1. ClingenBaseline 28 Oct 2026
      7 Missense p.(Val130Phe) 5 1

      GroupID: 7

      DiseaseAssertion: VHL

      Group size: 6

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: N/A

      GroupAgeRange: N/A

      Group Info: Retrospective analysis of a longitudinal cohort of 21 VHL germline mutation carriers and retinal haemangioblastomas. All patients were categorized in two genotypic categories: missense mutations and truncating mutations. From this pedigree, 6 individuals were suspected of VHL disease. 5/6 individuals developed RH, while 1/6 did not.

      GroupPresentingHPOs: HP:0009711 (retinal capillary hemangioma)

      GroupHPOFreeText: 5/6 patients in this family with VHL disease presented with retinal capillary hemangioma.

      GroupNotHPOs: N/A

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: Table S1

      Variant: p.V130P (c.388G>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 496061, https://www.ncbi.nlm.nih.gov/clinvar/variation/496061/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: Chr3(GRCh37): g.10188245G>T

      MutationType: missense_variant; transversion

      CivicName: V130P (c.388G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline MutationType:missense_variant;transversion AssumedRefSeq:NM_000551.3 Familial SupplementalData DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma CivicName:V130P(c.388G>T) cDNAPosition:388 ProteinPosition:130 AminoAcidChange:VALtoPRO ClinVarID:Yes ClinVarID:496061 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    onlinelibrary.wiley.com/doi/10.1111/aos.14360
  64. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Whole‐exome sequencing and immunohistochemistry findings in von Hippel–Lindau disease
    2
    1. ClingenBaseline 28 Oct 2026
      Patient II‐1 was admitted to the Department of Urinary Surgery and Neurosurgery in October 2007 and again in December 2015. In the first hospitalization, a serendipitous left kidney mass was found, but no symptoms. Abdominal CT revealed a solid cystic mass on the inside of the left kidney with irregular enhancement (Figure ​(Figure2b),2b), indicating a radiological diagnosis of RCCC. A laparoscopic radical nephrectomy was performed, and pathology confirmed the diagnosis of clear cell carcinoma. In the second hospitalization, the patient was admitted with complaints of headache and dizziness for 2 months. A brain MRI showed a right CH (Figure ​(Figure2c).2c). Tumor resection was performed through a posterior approach, and pathology confirmed the diagnosis of hemangioblastoma. In the most recent follow‐up, his symptoms had disappeared, and radiological imaging revealed no recurrence in either the brain or abdomen.

      PatientID: II-1

      KindredID: 1

      Case: M, 45Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: Both of the patient’s brothers (Patient II-3 and II-4), the patient’s sister (II-5), and the patient’s nephew (III-3) were clinically diagnosed with VHL disease. Patient II-4 presented with RCCC at age 53, and carried the mutation NM_000551.3:c.269A>T. Patient III-3 presented with CH and carried the same mutation. The patient’s other brother (Patient II‐3) and sister (Patient II‐5) were deceased and had an undetermined mutation. Patient II-3 died of an advanced RCCC, and Patient II‐5 died of a ruptured CH. The patient’s parents (Patient I-1 and I-2) were also deceased from other causes. The patient’s grand-nephew (Patient IV‐1) was healthy and did not carry the mutation.

      CasePresentingHPOs: HP:0006770; HP:0006880 (Renal clear cell carcinoma, cerebellar hemangioblastoma)

      CaseHPOFreeText: The 45Y male patient was diagnosed with left RCCC at 33Y, but had no symptoms. The patient presented with complaints of headache and dizziness at age 41Y, and was diagnosed with a right cerebellar hemangioblastoma. In the most recent follow‐up, his symptoms had disappeared, and radiological imaging of the brain and abdomen revealed no recurrence.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: Supplementary Table 1&2 gives information on genetic mutations observed in the CH and RCC tissues of this patient.

      Variant: p.N90I (c.269A>T)

      LegacyVariant: N/A

      ClinVarID: 223172, https://www.ncbi.nlm.nih.gov/clinvar/variation/223172/

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: N90I(c.269A>T)

      MultipleGeneVariants: Supplementary Table 1&2 gives information on genetic mutations observed in the CH and RCC tissues of this patient

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:cerebellarhemangioblastoma DiseaseEntity:clearcellrenalcellcarcinoma AgeOfPresentation:clearcellrenalcellcarcinoma:33 AgeOfPresentation:cerebellarhemangioblastoma:41 Mutation:Germline RefSeq:NM_000551 cDNAposition:269 ProteinPosition:90 AminoAcidChange:ASNtoILE ClinVarID:Yes ClinVarID:223172 MutationType:missense_variant;transversion CivicName:N90I(c.269A>T) FamilyPedigree Familial RefSeq:NM_000551.3 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 23 Oct 2026
      The proband (Patient III‐1) was admitted into our ward in October 2015 with a complaint of an occipital headache for 1 month. He was conscious, and a physical examination did not reveal ataxia. Tests for cranial nerve function, limb sensation and motor function were unremarkable. Contrast‐enhanced brain magnetic resonance imaging (MRI) revealed a solid‐cystic mass in the vermis cerebelli and left cerebellar hemisphere (Figure ​(Figure2a),2a), indicating a radiological diagnosis of CH. Cerebellar tumor resection was performed through a sub‐occipital craniotomy under general anesthesia, and the tumor was completely removed. The tumor, which was 30 mm in diameter, was pink and soft and composed of dilated veins and dense blood capillaries. A postoperative pathological analysis of the tumor indicated a hemangioblastoma. The patient completed outpatient follow‐up in October 2018. The occipital headache had disappeared, brain MRI showed no recurrence, and abdominal computerized tomography (CT) revealed no neoplasms.

      PatientID: III-3

      KindredID: 1

      Case: M, 25Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: Both of the patient’s uncles (Patient II-1 and II-4) were clinically diagnosed with VHL disease, and carried the mutation NM_000551.3:c.269A>T. Patient II-1 presented with RCCC at age 33 and cerebral hemangioblastoma at age 41. Patient II-4 presented with RCCC at age 53. The patient’s deceased father (Patient II‐3) and deceased aunt (Patient II‐5) were also clinically diagnosed with VHL disease, but the mutation was undetermined before death. His father died of advanced RCCC, and his aunt (Patient II‐5) died of a ruptured CH. The patient’s grandparents (Patient I-1 and I-2) were also deceased from other causes. The patient’s son (Patient IV‐1), wife (Patient III‐2), and mother (Patient II‐2) were healthy and did not carry the mutation. Their annual physical examination did not reveal a hemangioblastoma, kidney mass or abdominal cyst.

      CasePresentingHPOs: HP:0006880 (Cerebellar hemangioblastoma)

      CaseHPOFreeText: The 25Y male patient presented with occipital headache at 21Y. Upon initial examination, the patient was diagnosed with cerebellar hemangioblastoma and the tumour was resected. The patient completed outpatient follow‐up three years later. The occipital headache had disappeared, brain MRI showed no recurrence, and abdominal CT revealed no neoplasms.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.N90I (c.269A>T)

      LegacyVariant: N/A

      ClinVarID: 223172, https://www.ncbi.nlm.nih.gov/clinvar/variation/223172/

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: N90I(c.269A>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:cerebellarhemangioblastoma AgeOfPresentation:cerbellarhemangioblastoma:21 Mutation:Germline RefSeq:NM_000551 cDNAposition:269 ProteinPosition:90 AminoAcidChange:ASNtoILE CivicName:N90I(c.269A>T) ClinVarID:Yes ClinVarID:223172 MutationType:missense_variant;transversion FamilyPedigree Familial RefSeq:NM_000551.3 inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC6732316/
  65. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Germline mutations of the VHL gene in seven Chinese families with von Hippel-Lindau disease
    1
    1. ClingenBaseline 28 Oct 2026
      Disease-associated genetic abnormalities were identified in all of the seven families examined.

      PatientID: proband

      KindredID: D

      Case: F, 34Y0M, Chinese

      DiseaseAssertion: VHL

      FamilyInfo: Family history is said to be positive, however no other members were given. The patient’s son was asymptomatic and negative for the mutation.

      CasePresentingHPOs: HP:0010797 (hemangioblastoma)

      CaseHPOFreeText: Patient had multiple hemangioblastoma of the CNS diagnosed at 34Y

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.Q145* (c.433C>T)

      LegacyVariant: p.Q145* (c.646C>T)

      CaseProblemVariantFreeText: N/A

      ClinVarID: 625249 https://www.ncbi.nlm.nih.gov/clinvar/variation/625249/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: Q145* (c.433C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Chinese DiseaseEntity:VHL DiseaseEntity:hemangioblastoma Mutation:Germline AssumedRefSeq:AF010238.1 AgeOfPresentation:hemangioblastoma:34 MutationType:stop_gained ProteinPosition:145 CivicName:Q145*(c.433C>T) cDNAposition:433 AminoAcidChange:GLNtoTER ClinVarID:625249 ClinVarID:Yes Familial inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/21972040/
  66. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    New Insights Into Pheochromocytoma Surveillance of Young Patients With VHL Missense Mutations
    2
    1. ClingenBaseline 28 Oct 2026
      231616N—Y17NNYYYc.74C>Tb; 256C>A

      PatientID: 23

      KindredID: 16

      Case: Sex Unknown, 17Y0M, Brazilian (Latino/Admixed American)

      DiseaseAssertion: VHL

      FamilyInfo: None

      CasePresentingHPOs: HP:0030405; HP:0010797; HP:0001737; HP:0009711 (pancreatic endocrine tumor, hemangioblastoma, pancreatic cyst, retinal capillary hemangioma)

      CaseHPOFreeText: The patient developed a 2.2 cm PNET at age 17. Patient was also recorded with all of the above manifestations

      CaseNotHPOs: HP:0002668, HP:0002666; HP:0005584; HP:0000107 (Paraganglioma, pheochromocytoma, renal cell carcinoma, renal cyst)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.P86T (256C>A)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: N/A

      CAID: CA351750624 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.256C%3EA

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: P25L (c.74C>T) and P86T (c.256C>A)

      MultipleGeneVariants: Germline, VHL, c.74C>T (p.Pro25Leu)

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:pancreaticendocrinetumor DiseaseEntity:pancreaticcysts DiseaseEntity:hemangioblastoma DiseaseEntity:retinalcapillaryhemangioma AgeOfPresentation:pancreaticendocrinetumor:17 Mutation:Germline AssumedRefSeq:NM_000551.3 CAID:CA351750624 ClinVarID:N/A MutationType:missense_variant;transversion ProteinPosition:86 cDNAposition:256 CivicName:P25L(c.74C>T)andP86T(c.256C>A) CivicName:P86T(c.256C>A) AminoAcidChange:PROtoTHR NoFamilyInfo Ethnicity:Brazilian Ethnicity:Latino/AdmixedAmerican MultipleVHLVariants inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
    2. ClingenBaseline 23 Oct 2026
      221519N—N—NNYYNc.481C>T

      PatientID: 22

      KindredID: 15

      Case: Sex Unknown, 19Y0M, Brazilian (Latino/Admixed American)

      DiseaseAssertion: VHL

      FamilyInfo: none

      CasePresentingHPOs: HP:0010797; HP:0001737 (hemangioblastoma, pancreatic cyst)

      CaseHPOFreeText: N/A

      CaseNotHPOs: HP:0002668, HP:0002666; HP:0009711; HP:0030405; HP:0005584; HP:0000107 (Paraganglioma, pheochromocytoma, retinal capillary hemangioma, pancreatic endocrine tumor, renal cell carcinoma, renal cyst)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R161* (c.481C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 2217 https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: R161* (c.481C>T)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL InheritancePattern:AutosomalDominant Mutation:Germline AssumedRefSeq:NM_000551.3 DiseaseEntity:hemangioblastoma DiseaseEntity:pancreaticcysts ProteinPosition:161 cDNAposition:481 CivicName:R161*(c.481C>T) MutationType:stop_gained AminoAcidChange:ARGtoTER ClinVarID:2217 ClinVarID:Yes NoFamilyInfo Ethnicity:Brazilian Ethnicity:Latino/AdmixedAmerican inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC6735756/
  67. onlinelibrary.wiley.com onlinelibrary.wiley.com
    Genotype–phenotype correlations in von Hippel-Lindau disease
    1
    1. ClingenBaseline 28 Oct 2026

      GroupID: 11

      DiseaseAssertion: assumed VHL

      GroupSize: 9

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: N/A

      GroupAgeRange: N/A

      GroupInfo: 9 of the 573 patients discussed in this paper were found to the mutation belonging to 3 families, all with this mutation

      GroupPresentingHPOs: HP:0006880; HP:0005584; HP:0009711 (cerebellar hemangioblastoma, renal cell carcinoma; retinal capillary hemangioma)

      GroupHPOFreeText: 7 patients had retinal angiomas diagnosed at a mean age of 23Y, and 3 patients had cerebellar hemangioblastomas diagnosed at a mean age of 29Y. 5 patients had RCCs with a mean age of diagnosis of 43Y.

      GroupNotHPOs: HP:0002666 (pheochromocytoma)

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: Supplementary Table S1.

      Variant: p.Q73* (c.217C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 223164 https://www.ncbi.nlm.nih.gov/clinvar/variation/223164/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: Q73* (c.217C>T)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:cerebellarhemangioblastoma DiseaseEntity:renalcellcarcinoma DiseaseEntity:retinalcapillaryhemangioma ProteinPosition:73 CivicName:Q73*(c.217C>T) cDNAposition:217 MutationType:stop_gained AminoAcidChange:GLNtoTER ClinVarID:223164 ClinVarID:Yes Mutation:Germline RefSeq:NM_000551.2 ExperimentalAssay InheritancePattern:AutosomalDominant SupplementalData inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    onlinelibrary.wiley.com/doi/abs/10.1002/humu.20385
  68. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Identification of intragenic mutations in the Von Hippel — Lindau disease tumour suppressor gene andcorrelation with disease phenotype
    2
    1. ClingenBaseline 28 Oct 2026

      KindredID: 116

      GroupID: 41

      GroupSize: Unknown

      GroupNumberMales: Unknown

      GroupNumberFemales: Unknown

      GroupEthnicity: Unknown

      GroupAgeRange: Unknown

      DiseaseAssertion: VHL

      GroupInfo: Kindred no.116 describes a family where at least one member (unspecified how many) had this mutation in the VHL gene. Family history indicates that pheochromocytoma is present in this kindred.

      GroupPresentingHPOs: HP:0002666 (Pheochromocytoma)

      GroupHPOFreeText: This study investigated the frequency of different mutation classes between kindreds with and without pheochromocytoma. No other information about disease presentation within members of a kindred could be inferred.

      GroupNotHPOs: N/A

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: c.712C>T (p.R238W)

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL Mutation:Germline RefSeq:AF010238.1 cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP DiseaseEntity:pheochromocytoma ClinVarID:2218 ClinVarID:Yes MutationType:missense_variant;transition CivicName:R167W(c.499C>T) FamilyCohort inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 28 Oct 2026

      KindredID: 95

      GroupID: 40

      GroupSize: Unknown

      GroupNumberMales: Unknown

      GroupNumberFemales: Unknown

      GroupEthnicity: Unknown

      GroupAgeRange: Unknown

      DiseaseAssertion: VHL

      GroupInfo: Kindred no.95 describes a family where at least one member (unspecified how many) had this mutation in the VHL gene. Family history indicates that pheochromocytoma is present in this kindred.

      GroupPresentingHPOs: HP:0002666 (Pheochromocytoma)

      GroupHPOFreeText: This study investigated the frequency of different mutation classes between kindreds with and without pheochromocytoma. No other information about disease presentation within members of a kindred could be inferred.

      GroupNotHPOs: N/A

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: c.712C>T (p.R238W)

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL Mutation:Germline RefSeq:AF010238.1 cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP DiseaseEntity:pheochromocytoma ClinVarID:2218 ClinVarID:Yes MutationType:missense_variant;transition CivicName:R167W(c.499C>T) FamilyCohort inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/7987306/
  69. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Clinical and Genetic Investigation of a Multi-generational Chinese Family Afflicted with Von Hippel-Lindau Disease
    2
    1. ClingenBaseline 28 Oct 2026
      PatientsThe Chinese family study included five-generations comprising of 38 living family members, of whom nine were affected [Figure 1]. All living members were examined clinically. The clinical and radiographic images were published with the consent of the patient. The study was approved by the research Ethics Committees of Xi’an Jiaotong University School of Medicine. Written informed consents were obtained from all participants.Open in a separate windowFigure 1Haplotypes of the Chinese family affected by Von Hippel-Lindau (VHL). The open and filled blackened symbols indicated unaffected and affected individuals, respectively. The squares and circles symbolized the males and females, respectively. The proband, IV-3, was indicated by an arrow. The haplotyping was conducted using three polymorphic microsatellite markers. The marker order was determined from the Marshfield map and the UCSC Human Genome database (February 2009). The dark boxes symbolized haplotypes that cosegregated with the affected individuals and suggested linkage of VHL to disease in this family. The boxes with slash symbolized the dead family members.

      PatientID: III:12

      KindredID: 1

      Case: M, Age Unknown (deceased), Chinese

      DiseaseAssertion: VHL

      FamilyInfo: A 5-generation family with VHL in 15 members. Both second generation children (presumed), 5 third generation, and 8 further generation individuals were affected and haplotyping was conducted using three polymorphic microsatellite markers. All of the 5th generation children (9 total at time of publication) had been sequenced and haplotyped as unaffected.

      CasePresentingHPOs: N/A

      CaseHPOFreeText: unknown phenotype, however they were said to be affected

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: Death before genetic diagnostic, however presumed by authors due to extensive family history (See pedigree).

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Chinese DiseaseEntity:VHL Mutation:Germline AssumedRefSeq:NM_000551.3 CivicName:R167W(c.499C>T) cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP MutationType:missense_variant;transition ClinVarID:2218 ClinVarID:Yes Familial FamilyPedigree inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 25 Oct 2026
      PatientsThe Chinese family study included five-generations comprising of 38 living family members, of whom nine were affected [Figure 1]. All living members were examined clinically. The clinical and radiographic images were published with the consent of the patient. The study was approved by the research Ethics Committees of Xi’an Jiaotong University School of Medicine. Written informed consents were obtained from all participants.Open in a separate windowFigure 1Haplotypes of the Chinese family affected by Von Hippel-Lindau (VHL). The open and filled blackened symbols indicated unaffected and affected individuals, respectively. The squares and circles symbolized the males and females, respectively. The proband, IV-3, was indicated by an arrow. The haplotyping was conducted using three polymorphic microsatellite markers. The marker order was determined from the Marshfield map and the UCSC Human Genome database (February 2009). The dark boxes symbolized haplotypes that cosegregated with the affected individuals and suggested linkage of VHL to disease in this family. The boxes with slash symbolized the dead family members.

      PatientID: III:1

      KindredID: 1

      Case: M, Age Unknown (deceased), Chinese

      DiseaseAssertion: VHL

      FamilyInfo: A 5-generation family with VHL in 15 members. Both second generation children (presumed), 5 third generation, and 8 further generation individuals were affected and haplotyping was conducted using three polymorphic microsatellite markers. All of the 5th generation children (9 total at time of publication) had been sequenced and haplotyped as unaffected.

      CasePresentingHPOs: N/A

      CaseHPOFreeText: unknown phenotype, however they were said to be affected

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: Death before genetic diagnostic, however presumed by authors due to extensive family history (See pedigree).

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Chinese DiseaseEntity:VHL Mutation:Germline AssumedRefSeq:NM_000551.3 ProteinPosition:167 CivicName:R167W(c.499C>T) cDNAposition:499 AminoAcidChange:ARGtoTRP MutationType:missense_variant;transition ClinVarID:2218 ClinVarID:Yes Familial FamilyPedigree inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC4837816/
  70. onlinelibrary.wiley.com onlinelibrary.wiley.com
    Uncommon clinical presentations of pheochromocytoma and paraganglioma in two different patients affected by two distinct novel VHL germline mutations
    1
    1. ClingenBaseline 28 Oct 2026
      T152I missense mutation

      PatientID: None (mother)

      KindredID: 2

      Case: F, 48Y0M, Ethnicity Unknown

      DiseaseAssertion: asymptomatic

      FamilyInfo: Her 2 daughters were found to carry the same mutation. One daughter was asymptomatic too, while the other (aged 25Y) was operated on for a carotid body tumour.

      CasePresentingHPOs: None

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: An extensive clinical/physical examination was conducted: laboratory tests (urinary metanephrine and normetanephrine, plasma chromogranin A), an ophthalmoscopic examination and radiological exams (NMR of the brain, CT scan of the thorax and the abdomen) - all tests were normal.

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.T152I (c.455C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: N/A

      CAID: CA351754382 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.455C%3ET

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: T152I (c.455C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:asymptomatic Mutation:Germline AssumedRefSeq:NM_000551.3 CivicName:T152I(c.455C>T) cDNAposition:455 ProteinPosition:152 CAID:CA351754382 ClinVarID:N/A AminoAcidChange:THRtoILE MutationType:missense_variant;transition Familial FamilyPedigree ExperimentalAssay inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2265.2007.03131.x
  71. www-sciencedirect-com.proxy1.lib.uwo.ca www-sciencedirect-com.proxy1.lib.uwo.ca
    Higher Prevalence of Novel Mutations in VHL Gene in Chinese Von Hippel-Lindau Disease Patients
    1
    1. ClingenBaseline 28 Oct 2026
      Family 5+1c.217C > T, p.Gln73stopYes1––3754––

      PatientID: None

      KindredID: 5

      Case: Sex Unknown, 54, Chinese

      DiseaseAssertion:VHL

      FamilyInfo: Positive. The patient's nephew and niece although did not undergo genetic testing, presented with VHL associated conditions. The nephew had renal cell carcinoma at age 34 and cysts or tumours of the pancreas at age 37. The niece had renal cell carcinoma and cysts or tumours of the pancreas at age 35.

      CasePresentingHPOs: HP:0005584, HP:0001732 (renal cell carcinoma, abnormality of the pancreas)

      CaseHPOFreeText: The patient had renal cell carcinoma at age 37 and cysts or tumours of the pancreas at age 54.

      CaseNotHPOs: HP:0002666, HP:0009715, HP:0010797, HP:000971(pheochromocytoma, Papillary cystadenoma of the epididymis, hemangioblastoma, retinal capillary hemangioma)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: 29330336

      SupplementalData: N/A

      Variant: p.Q73* (c.217C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 223164 https://www.ncbi.nlm.nih.gov/clinvar/variation/223164/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence:N/A

      MutationType: stop_gained

      CivicName: Q73* (c.217C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline AssumedRefSeq:NM_000551.3 DiseaseEntity:VHL Familial Ethnicity:Chinese DiseaseEntity:renalcellcarcinoma DiseaseEntity:abnormalityofthepancreas AgeOfPresentation:renalcellcarcinoma:37 AgeOfPresentation:abnormalityofthepancreas:54 cDNAposition:217 CivicName:Q73*(c.217C>T) ProteinPosition:73 AminoAcidChange:GLNtoTER MutationType:stop_gained ClinVarID:223164 ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    www-sciencedirect-com.proxy1.lib.uwo.ca/science/article/pii/S0090429513014969
  72. link.springer.com link.springer.com
    Retinal angiomatosis and von Hippel-Lindau disease
    1
    1. ClingenBaseline 28 Oct 2026

      GroupID: None (12)

      DiseaseAssertion: VHL

      GroupSize: 1

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: N/A

      GroupAgeRange: N/A

      GroupInfo: This family group of 1 individual has clinically confirmed VHL disease presenting with retinal angiomatosis. This individual was found to harbor a c.278G>T variant causing a Gly93Val missense mutation (noted in the paper as c.491G>T due to Latif reference transcript being used).

      GroupPresentingHPOs: HP:0009711 (Retinal capillary hemangioma)

      GroupHPOFreeText: Patients within this family were found to have a clinical diagnosis of VHL disease. No VHL clinical phenotypes were explicitly stated other than retinal angiomatosis.

      GroupNotHPOs: N/A

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.G93V (c.278G>T)

      LegacyVariant: c.491G>T

      CaseProblemVariantFreeText: N/A

      ClinVarID: 625232, https://www.ncbi.nlm.nih.gov/clinvar/variation/625232/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: G93V (c.278G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma Mutation:Germline AssumedRefSeq:AF010238.1 cDNAposition:278 ProteinPosition:93 AminoAcidChange:GLYtoVAL ClinVarID:625232 ClinVarID:Yes MutationType:missense_variant;transversion CivicName:G93V(c.278G>T) NoFamilyInfo FamilyCohort inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    link.springer.com/article/10.1007/s004170000200
  73. www.thieme-connect.de www.thieme-connect.de
    Pheochromocytoma and Von Hippel–Lindau in Pregnancy
    1
    1. ClingenBaseline 28 Oct 2026

      PatientID: None (proband’s brother)

      KindredID: 2

      Case: M, Age Unknown, Ethnicity unknown

      DiseaseAssertion: VHL

      FamilyInfo: His sister (25Y0M; proband), dad, and 8-year-old nephew have also been diagnosed with VHL. His other infant nephew also tested positive for the VHL mutation (c.499C>T).

      CasePresentingHPOs: unknown

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218 https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954 https://gnomad.broadinstitute.org/variant/3-10191506-C-T

      VariantEvidence: N/A

      MutationType: missense_variant; transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL Mutation:Germline AssumedRefSeq:NM_000551.3 CivicName:R167W(c.499C>T) cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP MutationType:missense_variant;transition ClinVarID:2218 ClinVarID:Yes Familial inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    thieme-connect.de/products/ejournals/abstract/10.1055/s-0029-1239489
  74. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Family history of von Hippel–Lindau disease was uncommon in Chinese patients: suggesting the higher frequency of de novo mutations in VHL gene in these patients
    2
    1. ClingenBaseline 28 Oct 2026

      PatientID: N/A

      KindredID: 2

      Case: F, 8Y0M, Chinese

      DiseaseAssertion: Asymptomatic

      FamilyInfo: Patient had no family history of VHL disease. Her parent had the same VHL mutation and presented with retinal capillary hemangioma, renal cell carcinoma, abnormality of the pancreas, and pheochromocytoma.

      CohortInfo: 16 Chinese patients clinically diagnosed with VHL disease.

      CasePresentingHPOs: N/A

      CaseHPOFreeText: N/A

      CaseNotHPOs: HP:0009711, HP:0002666, HP:0030393, HP:0010797, HP:0006770, HP:0001732 (retinal capillary hemangioma, pheochromocytoma, endolymphatic sac tumor, hemangioblastoma, clear cell renal cell carcinoma, abnormality of the pancreas)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.P86S (c.256C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 178692, https://www.ncbi.nlm.nih.gov/clinvar/variation/178692/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transition

      CivicName: P86S (c.256C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline MutationType:missense_variant;transition AssumedRefSeq:AF010238.1 Ethnicity:Chinese Familial DiseaseEntity:asymptomatic cDNAPosition:256 CivicName:P86S(c.256C>T) ProteinPosition:86 AminoAcidChange:PROtoSER ClinVarID:Yes ClinVarID:178692 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 28 Oct 2026
      16 patients

      PatientID: 10

      KindredID: 10

      Case: Sex Unknown, 55Y0M, Chinese

      DiseaseAssertion: VHL

      FamilyInfo: Patient had family history of VHL disease. Patient’s son presented with epididymal cystadenoma at age 23 and possessed the same mutation. Patient’s daughter had no clinical manifestations but also had the same VHL mutation.

      CohortInfo: 16 Chinese patients clinically diagnosed with VHL disease.

      CasePresentingHPOs: HP:0010797; HP:0005584; HP:0001732 (hemangioblastoma; renal cell carcinoma; abnormality of the pancreas)

      CaseHPOFreeText: The patient presented with multiple pancreatic cysts or tumors and renal cell carcinoma at age 53 and a hemangioblastoma at age 54.

      CaseNotHPOs: HP:0009711, HP:0030424, HP:0002666, HP:0030393 (retinal capillary hemangioma, epididymal cyst, pheochromocytoma, endolymphatic sac tumor)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.E94* (c.280G>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 584477, https://www.ncbi.nlm.nih.gov/clinvar/variation/584477/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: E94* (c.280G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline MutationType:stop_gained AssumedRefSeq:NM_000551.3 Ethnicity:Chinese Familial DiseaseEntity:VHL DiseaseEntity:hemangioblastoma DiseaseEntity:renalcellcarcinoma DiseaseEntity:abnormalityofthepancreas AgeOfPresentation:abnormalityofthepancreas:53 AgeOfPresentation:renalcellcarcinoma:53 AgeOfPresentation:hemangioblastoma:54 CivicName:E94*(c.280G>T) cDNAPosition:280 ProteinPosition:94 AminoAcidChange:GLUtoTER ClinVarID:Yes ClinVarID:584477 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/22357542/
  75. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Somatic inactivation of the VHL gene in Von Hippel-Lindau disease tumors.
    4
    1. ClingenBaseline 28 Oct 2026

      PatientID: 1

      KindredID: 96

      Case: Sex, Age, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0005584 (renal cell carcinoma)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167* (c.481C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: p.R167* (c.694C>T)

      ClinVarID: 2217 https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: Loss of heterozygosity

      MutationType: stop_gained

      CivicName: R167* (c.481C>T)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:renalcellcarcinoma Mutation:Germline RefSeq:AF010238.1 CivicName:R161*(c.481C>T) cDNAposition:481 AminoAcidChange:ARGtoTER ClinVarID:2217 MutationType:stop_gained ProteinPosition:161 ClinVarID:Yes InheritancePattern:AutosomalDominant NoFamilyInfo inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 28 Oct 2026

      PatientID: 1

      KindredID: P30

      Case: Sex, Age, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0002666 (pheochromocytoma)

      CaseHPOFreeText: a pheochromocytoma was detected in this patient

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: p.R167W (c.712C>T)

      ClinVarID: 2218 (https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/)

      CAID: N/A

      gnomAD: 0.000007954 https://gnomad.broadinstitute.org/variant/3-10191506-C-T

      VariantEvidence: Tested the tumors for somatic mutations but did not detect any

      MutationType: missense_variant; transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:pheochromocytoma NoFamilyInfo InheritancePattern:AutosomalDominant RefSeq:AF010238.1 Mutation:Germline CivicName:R167W(c.499C>T) cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP MutationType:missense_variant;transition ClinVarID:2218 ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    3. ClingenBaseline 28 Oct 2026

      PatientID: 2

      KindredID: P1

      Case: Sex, Age, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: One other patient belonging to the same family (P1) had this mutation. They had 1 HB and 1 pheochromocytoma

      CasePresentingHPOs: HP:0006880 (cerebellar hemangioblastoma)

      CaseHPOFreeText: two cerebellar hemangioblastomas were detected in this patient

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: p.R167W (c.712C>T)

      ClinVarID: 2218 (https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/)

      CAID: N/A

      gnomAD: 0.000007954 https://gnomad.broadinstitute.org/variant/3-10191506-C-T

      VariantEvidence: Tested the tumors for somatic mutations but did not detect any

      MutationType: missense_variant; transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:cerebellarhemangioblastoma InheritancePattern:AutosomalDominant Familial Mutation:Germline RefSeq:AF010238.1 ClinVarID:2218 ClinVarID:Yes CivicName:R167W(c.499C>T) cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP MutationType:missense_variant;transition inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    4. ClingenBaseline 27 Oct 2026

      PatientID: 1

      KindredID: P3

      Case: Sex, Age, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0010797 (hemangioblastoma)

      CaseHPOFreeText: HB1 and HB2 were detected in this patient (P3/1)

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167* (c.481C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: p.R167* (c.694C>T)

      ClinVarID: 2217 https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: R167* (c.481C>T)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:hemangioblastoma AminoAcidChange:ARGtoTER CivicName:R161*(c.481C>T) cDNAposition:481 Mutation:Germline RefSeq:AF010238.1 MutationType:stop_gained ClinVarID:2217 ProteinPosition:161 ClinVarID:Yes InheritancePattern:AutosomalDominant NoFamilyInfo inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC1712486/
  76. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Genotype-phenotype correlations in Chinese von Hippel–Lindau disease patients
    4
    1. ClingenBaseline 28 Oct 2026

      PatientID: 93

      KindredID: 30

      Case: M, 31Y0M, Chinese

      DiseaseAssertion: VHL

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0010797; (Hemangioblastoma)

      CaseHPOFreeText: The proband presented with a CNS hemangioblastoma at age 51.

      CaseNotHPOs: HP:0002666; HP:0009711; HP:0005584; HP:0001737; HP:0001732 (Pheochromocytoma, Retinal capillary hemangioma, Renal cell carcinoma, Pancreatic cysts, Abnormality of the pancreas)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: This patient was also published in a later paper by Wang et al., 2018 (PMID: 29330336).

      SupplementalData: Patient and family genotype-phenotype information is listed in Supplementary Table 1.

      Variant: p.E94* (c.280G>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 584477; https://www.ncbi.nlm.nih.gov/clinvar/variation/584477/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: E94* (c.280G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Chinese Mutation:Germline AssumedRefSeq:NM_000551.3 DiseaseEntity:VHL DiseaseEntity:hemangioblastoma AgeOfPresentation:hemangioblastoma:31 CivicName:E94*(c.280G>T) cDNAposition:280 ProteinPosition:94 AminoAcidChange:GLUtoTER ClinVarID:584477 ClinVarID:Yes MutationType:missense_variant;transversion SupplementalData inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 25 Oct 2026

      PatientID: 200

      KindredID: 77

      Case: F, 25Y0M, Chinese

      DiseaseAssertion: VHL

      FamilyInfo: The proband (patient 200) has six family members who passed away before diagnosis/ had no DNA sample available. Of the family who passed away before diagnosis: the proband's aunt 1 (patient 202) had a CNS hemangioblastoma at 27; the daughter of aunt 1 (patient 203) had a pheochromocytoma at 31; aunt 2 (patient 205) had a CNS hemangioblastoma at 43, renal cell carcinoma at 36, and multiple pancreatic cysts/tumors at 48. Of the family for whom no DNA sample was available: the proband's mother (patient 201) had a CNS hemangioblastoma at 51, multiple pancreatic cysts/tumors at 46, and a pheochromocytoma at 25; the grandson of aunt 1 (patient 204) had a pheochromocytoma at age 9; and the son of aunt 2 (patient 206) had a pheochromocytoma at 16 and renal cell carcinoma + multiple pancreatic cysts/tumors at 21.

      CasePresentingHPOs: HP:0010797 (Hemangioblastoma)

      CaseHPOFreeText: The patient presented with a pheochromocytoma and renal cell carcinoma at 36.

      CaseNotHPOs: HP:0009711; HP:0001737; HP:0001732; HP:0002666; HP:0005584 (Retinal capillary hemangioma, Pancreatic cysts, Abnormality of the pancreas, Pheochromocytoma, Renal cell carcinoma )

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: This patient was also published in a later paper by Wang et al., 2018 (PMID: 29330336).

      SupplementalData: Patient and family genotype-phenotype information is listed in Supplementary Table 1.

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218; https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954; https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Chinese Mutation:Germline AssumedRefSeq:NM_000551.3 DiseaseEntity:VHL DiseaseEntity:hemangioblastoma AgeOfPresentation:hemangioblastoma:25 ClinVarID:2218 ClinVarID:Yes MutationType:missense_variant;transition CivicName:R167W(c.499C>T) Familial SupplementalData cDNAposition:449 ProteinPosition:167 AminoAcidChange:ARGtoTRP inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    3. ClingenBaseline 25 Oct 2026

      PatientID: 187

      KindredID: 72

      Case: M, 67Y0M, Chinese

      DiseaseAssertion: VHL

      FamilyInfo: The proband, patient 72, has multiple family members with the same mutation. Her father (patient 73) had a CNS hemangioblastoma at 65, renal cell carcinioma at 54, and multiple pancreatic cysts/tumors at 67. Her sister 2 (second sister) had multiple pancreatic cysts/tumors at 36, and a CNS hemangioblastoma at 39. Her sister 3 had multiple pancreatic cysts/tumors at 32, and a retinal angioma at 34. The proband's sister 1 had a CNS hemangioblastoma at 22, but passed away before they could be diagnosed/ confirmed with the mutation.

      CasePresentingHPOs: HP:0010797; HP:0005584; HP:0001732; HP:0001737 (Hemangioblastoma, Renal cell carcinoma, Abnormality of the pancreas, Pancreatic cysts)

      CaseHPOFreeText: The patient presented with a CNS hemangioblastoma at 65, renal cell carcinoma at 54, and multiple pancreatic cysts/tumors at 67.

      CaseNotHPOs: HP:0009711; HP:0002666 (Retinal capillary hemangioma, Pheochromocytoma)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: This patient was also published in a later paper by Wang et al., 2018 (PMID: 29330336).

      SupplementalData: Patient and family genotype-phenotype information is listed in Supplementary Table 1.

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218; https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954; https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Chinese Mutation:Germline AssumedRefSeq:NM_000551.3 DiseaseEntity:VHL DiseaseEntity:hemangioblastoma DiseaseEntity:renalcellcarcinoma DiseaseEntity:pancreaticcysts DiseaseEntity:abnormalityofthepancreas AgeOfPresentation:hemangioblastoma:65 AgeOfPresentation:renalcellcarcinoma:54 AgeOfPresentation:pancreaticcysts:67 AgeOfPresentation:abnormalityofthepancreas:67 ClinVarID:2218 ClinVarID:Yes MutationType:missense_variant;transition CivicName:R167W(c.499C>T) Familial SupplementalData cDNAposition:449 ProteinPosition:167 AminoAcidChange:ARGtoTRP inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    4. ClingenBaseline 24 Oct 2026

      PatientID: 186

      KindredID: 72

      Case: F, 39Y0M, Chinese

      DiseaseAssertion: VHL

      FamilyInfo: The proband, patient 72, has multiple family members with the same mutation. Her father (patient 73) had a CNS hemangioblastoma at 65, renal cell carcinioma at 54, and multiple pancreatic cysts/tumors at 67. Her sister 2 (second sister) had multiple pancreatic cysts/tumors at 36, and a CNS hemangioblastoma at 39. Her sister 3 had multiple pancreatic cysts/tumors at 32, and a retinal angioma at 34. The proband's sister 1 had a CNS hemangioblastoma at 22, but passed away before they could be diagnosed/ confirmed with the mutation.

      CasePresentingHPOs: HP:0010797; HP:0005584; HP:0001732; HP:0001737; HP:0002666 (Hemangioblastoma, Renal cell carcinoma, Abnormality of the pancreas, Pancreatic cysts, Pheochromocytoma)

      CaseHPOFreeText: The patient presented with a CNS hemangioblastoma, renal cell carcinoma, and multiple pancreatic cysts/tumors at 37, and a pheochromocytoma at 39.

      CaseNotHPOs: HP:0009711 (Retinal capillary hemangioma)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: This patient was also published in a later paper by Wang et al., 2018 (PMID: 29330336).

      SupplementalData: Patient and family genotype-phenotype information is listed in Supplementary Table 1.

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218; https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954; https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Chinese Mutation:Germline AssumedRefSeq:NM_000551.3 DiseaseEntity:VHL DiseaseEntity:hemangioblastoma DiseaseEntity:renalcellcarcinoma DiseaseEntity:abnormalityofthepancreas DiseaseEntity:pancreaticcysts DiseaseEntity:pheochromocytoma AgeOfPresentation:hemangioblastoma:37 AgeOfPresentation:renalcellcarcinoma:37 AgeOfPresentation:pheochromocytoma:39 AgeOfPresentation:pancreaticcysts:37 AgeOfPresentation:abnormalityofthepancreas:37 ClinVarID:2218 ClinVarID:Yes MutationType:missense_variant;transition CivicName:R167W(c.499C>T) Familial SupplementalData cDNAposition:449 ProteinPosition:167 AminoAcidChange:ARGtoTRP inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC5503545/
  77. onlinelibrary.wiley.com onlinelibrary.wiley.com
    Germline mutations in the von Hippel–Lindau disease tumor suppressor gene: Correlations with phenotype
    3
    1. ClingenBaseline 28 Oct 2026

      GroupID: 4405

      DiseaseAssertion: assumed VHL

      GroupSize: 41

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: N/A

      GroupAgeRange: N/A

      GroupInfo: Familial VHL stated; 41 family members recorded with this mutation.

      GroupPresentingHPOs: HP:0009711; HP:0010797; HP:0002666; HP:0005584 (retinal capillary hemangioma, hemangioblastoma, pheochromocytoma, renal cell carcinoma)

      GroupHPOFreeText: 29/41 members had retinal angioma (hemangioma), 10 had CNS hemangioblastoma, 15 had RCC and 28 had pheochromocytoma

      GroupNotHPOs: N/A

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: 8956040 (type 2 4405NCI)

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: p.R238W (c.712C>T)

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-

      VariantEvidence: N/A

      MutationType: missense_variant; transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:hemangioblastoma DiseaseEntity:renalcellcarcinoma DiseaseEntity:pheochromocytoma Mutation:Germline RefSeq:AF010238.1 ClinVarID:Yes ClinVarID:2218 InheritancePattern:AutosomalDominant Familial FamilyCohort CivicName:R167W(c.499C>T) cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP MutationType:missense_variant;transition inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 27 Oct 2026

      GroupID: 2753

      DiseaseAssertion: assumed VHL

      GroupSize: 7

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: N/A

      GroupAgeRange: N/A

      GroupInfo: Familial VHL stated; 7 family members recorded with this mutation.

      GroupPresentingHPOs: HP:0010797; HP:0009711; HP:0005584 (hemangioblastoma, retinal capillary hemangioma, renal cell carcinoma)

      GroupHPOFreeText: 6/7 members had a retinal angioma (hemangioma), 3 had RCC, and 1 member had CNS hemangioblastoma

      GroupNotHPOs: HP:0002666 (pheochromocytoma)

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: Possibly previously published in PMID: 9829911 [Q73* (c.217C>T) family (ID 20)]

      SupplementalData: N/A

      Variant: p.Q73* (c.217C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: p.Q73* (c.430C>T)

      ClinVarID: 223164 https://www.ncbi.nlm.nih.gov/clinvar/variation/223164

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: Q73* (c.217C>T)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:hemangioblastoma DiseaseEntity:renalcellcarcinoma Mutation:Germline RefSeq:AF010238.1 ClinVarID:Yes ClinVarID:223164 InheritancePattern:AutosomalDominant Familial FamilyCohort MutationType:stop_gained AminoAcidChange:GLNtoTER ProteinPosition:73 CivicName:Q73*(c.217C>T) cDNAposition:217 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    3. ClingenBaseline 23 Oct 2026

      PatientID: None

      KindredID: 4479

      Case: Sex, Age, Ethnicity Unknown

      DiseaseAssertion: assumed VHL

      FamilyInfo: Familial VHL stated; although only 1 family member recorded.

      CasePresentingHPOs: HP:0010797 (hemangioblastoma)

      CaseHPOFreeText: N/A

      CaseNotHPOs: HP:0002666; HP:0009711; HP:0005584 (Pheochromocytoma, retinal capillary hemangioma, renal cell carcinoma)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: 8956040

      SupplementalData: N/A

      Variant: p.E70* (c.208G>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: p.E70* (c.421G>T)

      ClinVarID: 428806 https://www.ncbi.nlm.nih.gov/clinvar/variation/428806/

      CAID: CA16602179 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.208G%3ET

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: E70* (c.208G>T)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:hemangioblastoma Mutation:Germline CivicName:E70*(c.208G>T) cDNAposition:208 ProteinPosition:70 AminoAcidChange:GLUtoTER CAID:CA16602179 ClinVarID:428806 MutationType:stop_gained Familial RefSeq:AF010238.1 InheritancePattern:AutosomalDominant ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    onlinelibrary.wiley.com/doi/10.1002/humu.1380050109
  78. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Germline mutations in the Von Hippel-Lindau disease (VHL) gene in families from North America, Europe, and Japan
    5
    1. ClingenBaseline 28 Oct 2026
      Germline mutations were identified in 300/469 (63%) of the families tested; 137 distinct intragenic germline mutations were detected.

      GroupID/ KindredID: 55CE, 136CA

      DiseaseAssertion: VHL

      GroupSize: N/A

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: N/A

      GroupAgeRange: N/A

      GroupInfo: This germline familial VHL mutation was taken from the Munich, university of Freiburg and Institute of Pathology database and the Cambridge, Department of Pathology database, with an unknown number of members belonging to Family IDs 55CE and 136CA. Table 3 lists all ID and mutations associated with individuals possessing renal carcinoma, without pheochromocytoma.

      GroupPresentingHPOs: HP:0005548 (renal cell carcinoma)

      GroupHPOFreeText: Described as a VHL family with RCC, without pheochromocytoma. Other phenotypes are likely, however not detailed in this publication

      GroupNotHPOs: HP:0002666 (pheochromocytoma)

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R113* (c.337C>T)

      LegacyVariant: p.R113* (c.550C>T)

      CaseProblemVariantFreeText: N/A

      ClinVarID: 220414 https://www.ncbi.nlm.nih.gov/clinvar/variation/220414/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: This paper declares this variant is predicted to compromise the Elongin-binding site by truncating the protein.

      MutationType: stop_gained

      CivicName: R113* (c.337C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline RefSeq:AF010238.1 DiseaseEntity:renalcellcarcinoma ProteinPosition:113 AminoAcidChange:ARGtoTER CivicName:R113*(c.337C>T) cDNAposition:337 MutationType:stop_gained ClinVarID:220414 ClinVarID:Yes Familial FamilyCohort inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 28 Oct 2026
      Germline mutations were identified in 300/469 (63%) of the families tested; 137 distinct intragenic germline mutations were detected.

      GroupID/ KindredID: 70CA, 3699NCI

      DiseaseAssertion: VHL

      GroupSize: N/A

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: N/A

      GroupAgeRange: N/A

      GroupInfo: This germline familial VHL mutation was taken from two databases: the Cambridge, Department of Pathology database and the National Cancer Institute database. There was an unknown number of members belonging to Family IDs: 70CA and 3699NCI. Table 3 lists all ID and mutations associated with individuals possessing renal carcinoma, without pheochromocytoma.

      GroupPresentingHPOs: HP:0005548 (renal cell carcinoma)

      GroupHPOFreeText: Described as a VHL family with RCC, without pheochromocytoma. Other phenotypes are likely, however not detailed in this publication

      GroupNotHPOs: HP:0002666 (pheochromocytoma)

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: 7728151; 9829911

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: p.R167W (c.712C>T)

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218 https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954 https://gnomad.broadinstitute.org/variant/3-10191506-C-T

      VariantEvidence: This paper declares this variant is predicted to compromise the Elongin-binding site by location between codons 157 and 189.

      MutationType: missense_variant; transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline RefSeq:AF010238.1 DiseaseEntity:renalcellcarcinoma CivicName:R167W(c.499C>T) cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP MutationType:missense_variant;transition ClinVarID:2218 ClinVarID:Yes Familial FamilyCohort inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    3. ClingenBaseline 27 Oct 2026
      Germline mutations were identified in 300/469 (63%) of the families tested; 137 distinct intragenic germline mutations were detected.

      GroupID/ KindredID: 74CA, 2753NCI, 38CA

      DiseaseAssertion: VHL

      GroupSize: N/A

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: N/A

      GroupAgeRange: N/A

      GroupInfo: This germline familial VHL mutation was taken from the Cambridge, Department of Pathology database as well as the National Cancer Institute database with an unknown number of members belonging to Family ID 38CA, 74CA, 2753NCI. Table 3 lists all ID and mutations associated with individuals possessing renal carcinoma, without phechromocytoma.

      GroupPresentingHPOs: HP:0005548 (renal cell carcinoma)

      GroupHPOFreeText: Described as a VHL family with RCC, without pheochromocytoma. Other phenotypes are likely, however not detailed in this publication

      GroupNotHPOs: HP:0002666 (pheochromocytoma)

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: 7728151; 9829911

      SupplementalData: N/A

      Variant: p.Q73* (c.217C>T)

      LegacyVariant: p.Q73* (c.430C>T)

      CaseProblemVariantFreeText: N/A

      ClinVarID: 223164 https://www.ncbi.nlm.nih.gov/clinvar/variation/223164/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: This paper declares this variant is predicted to compromise the Elongin-binding site by truncating the protein.

      MutationType: stop_gained

      CivicName: Q73* (c.217C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline DiseaseEntity:renalcellcarcinoma RefSeq:AF010238.1 cDNAposition:217 CivicName:Q73*(c.217C>T) AminoAcidChange:GLNtoTER MutationType:stop_gained ProteinPosition:73 ClinVarID:223164 ClinVarID:Yes Familial FamilyCohort inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    4. ClingenBaseline 26 Oct 2026
      Germline mutations were identified in 300/469 (63%) of the families tested; 137 distinct intragenic germline mutations were detected.

      GroupID/ KindredID: 4783NCI

      DiseaseAssertion: VHL

      GroupSize: N/A

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: N/A

      GroupAgeRange: N/A

      GroupInfo: Two germline familial VHL mutations were associated with this family. They were: c.382C>T and c.381G>T and this data was taken from the National Cancer Institute database. It is unclear how many members belonging to Family ID 4783NCI had both mutations. Table 4 lists all ID and mutations associated with individuals with pheochromocytoma.

      GroupPresentingHPOs: HP:0002666 (pheochromocytoma)

      GroupHPOFreeText: Described as a VHL family with pheochromocytoma. Other phenotypes are likely, including renal cell carcinoma, however not detailed here.

      GroupNotHPOs: N/A

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.G127G (c.381G>T)

      LegacyVariant: p.G127G (c.594G>T)

      CaseProblemVariantFreeText: N/A

      ClinVarID: N/A

      CAID: CA432421824 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.381G>T

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transversion; synonymous_variant

      CivicName: G127G (c.381G>T)

      MultipleGeneVariants: Germline, VHL, c.382C>T (p.Leu128Phe)

      InheritancePattern:AutosomalDominant Mutation:Germline RefSeq:AF010238.1 DiseaseEntity:pheochromocytoma cDNAposition:381 ProteinPosition:127 AminoAcidChange:GLYtoGLY CivicName:G127G(c.381G>T) MutationType:missense_variant;transversion MutationType:synonymous_variant CAID:CA432421824 ClinVarID:N/A MultipleVHLVariants Familial FamilyCohort inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
    5. ClingenBaseline 24 Oct 2026
      Germline mutations were identified in 300/469 (63%) of the families tested; 137 distinct intragenic germline mutations were detected.

      GroupID/ KindredID: 40CA

      DiseaseAssertion: VHL

      GroupSize: N/A

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: N/A

      GroupAgeRange: N/A

      GroupInfo: This germline familial VHL mutation was taken from the Cambridge, Department of Pathology database, with an unknown number of members belonging to Family ID 40CA. Table 4 lists all ID and mutations associated with individuals with pheochromocytoma.

      GroupPresentingHPOs: HP:0002666 (pheochromocytoma)

      GroupHPOFreeText: Described as a VHL family with pheochromocytoma. Other phenotypes are likely, including renal cell carcinoma, however not detailed here.

      GroupNotHPOs: N/A

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.G114C (c.340G>T)

      LegacyVariant: p.G114C (c.553G>T)

      CaseProblemVariantFreeText: N/A

      ClinVarID: N/A

      CAID: CA351751376 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.340G>T

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transversion

      CivicName: G114C (c.340G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline RefSeq:AF010238.1 DiseaseEntity:pheochromocytoma ProteinPosition:114 cDNAposition:340 CivicName:G114C(c.340G>T) AminoAcidChange:GLYtoCYS MutationType:missense_variant;transversion CAID:CA351751376 ClinVarID:N/A Familial FamilyCohort inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/8956040/
  79. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Allelic deletion and mutation of the von Hippel-Lindau (VHL) tumor suppressor gene in pancreatic microcystic adenomas.
    1
    1. ClingenBaseline 28 Oct 2026
      In 2 cases, VHL disease was documented clinically

      PatientID: 2

      KindredID: 2

      Case: M, 38Y0M, ethnicity unknown

      DiseaseAssertion: VHL

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0001737; HP:0002666; HP:0005584 (Pancreatic cysts; pheochromocytoma; renal cell carcinoma)

      CaseHPOFreeText: Pancreatic microcyst adenomas (Pancreatic MCAs), and other VHL disease-associated tumors

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R161* (c.481C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: R161* (c.694C>T)

      ClinVarID: 2217 https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: See Table 2 (case 2) for LOH information

      MutationType: stop_gained

      CivicName: R161* (c.481C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:pancreaticcysts DiseaseEntity:pheochromocytoma DiseaseEntity:renalcellcarcinoma AssumedRefSeq:AF010238.1 Mutation:Germline CivicName:R161*(c.481C>T) cDNAposition:481 AminoAcidChange:ARGtoTER ProteinPosition:161 MutationType:missense_variant;transition ClinVarID:2217 ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC1858030/
  80. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Retinal abnormalities associated with a mutation of the nucleotide 683 in von Hippel-Lindau disease
    1
    1. ClingenBaseline 28 Oct 2026
      Methods: We performed a fundus examination and fluorescein and indocyanine green (ICG) angiography in both eyes of a young woman affected by VHL with bilateral pheochromocytoma, retinal angioma, retinal microaneurysms and unusual alterations of the deep retinal layers. A molecular analysis of the VHL gene was carried out.

      PatientID: 1 (case)

      KindredID: 1

      Case: F, 25Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: Not significant - the paper states that the parents and siblings were negative for the mutation (indicating de novo).

      CasePresentingHPOs: HP:0002666; HP:0009711; HP:0000479; HP:0012045 (pheochromocytoma, retinal capillary hemangioma, abnormal retinal morphology, retinal flecks)

      CaseHPOFreeText: patient was referred for eye exam as part of a VHL screening program at 25Y. She has been diagnosed with bilateral pheochromocytoma at the age of 14 after an episode of acute hypertensive encephalopathy. Ophthalmoscopy disclosed in her right eye a small retinal hemangioma (1 disc diameter wide) along with feeder vessels in the mid-periphery and multiple, small, whitish, dome-shaped lesions scattered in the deeper layers of the posterior retina. Fluorescein and indocyanine green angiography confirmed the presence of the retinal hemangioma; multiple window-defects were also seen at the posterior pole and pericentral retina and hypofluorescent dots. (Unusual alterations of the deep retinal layers).

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.T157I (c.470C>T)

      LegacyVariant: p.T157I (c.683C>T)

      CaseProblemVariantFreeText: N/A

      ClinVarID: 223223 https://www.ncbi.nlm.nih.gov/clinvar/variation/223223/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: T157I (c.470C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:DeNovoAssertion deNovoConfirmed DiseaseEntity:VHL DiseaseEntity:pheochromocytoma DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:retinalflecks DiseaseEntity:abnormalretinalmorphology AgeOfPresentation:pheochromocytoma:14 AgeOfPresentation:retinalcapillaryhemangioma:25 Mutation:Germline AssumedRefSeq:AF010238.1 cDNAposition:470 ProteinPosition:157 AminoAcidChange:THRtoILE CivicName:T157I(c.470C>T) MutationType:missense_variant;transition ClinVarID:223223 ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/10955664/
  81. pubmed-ncbi-nlm-nih-gov.proxy1.lib.uwo.ca pubmed-ncbi-nlm-nih-gov.proxy1.lib.uwo.ca
    Efficacy of gene testing for von Hippel-Lindau disease
    1
    1. ClingenBaseline 28 Oct 2026

      PatientID: 2

      KindredID: 2

      Case: Sex Unknown, Age Unknown, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: Positive.

      CohortInfo: Between September 1994 and December 1997, 16 unrelated individuals were referred to Genetic Services of Western Australia by local clinicians and by similar genetic services in other States, for VHL gene mutation analysis because of clinical manifestations suggestive of the diagnosis.

      CasePresentingHPOs: HP:0002666, HP:0009711, HP:0010797 (pheochromocytoma, retinal capillary hemangioma, hemangioblastoma)

      CaseHPOFreeText: N/A

      CaseNotHPOs: HP:0005584, HP:0001737 (renal cell carcinoma, pancreatic cysts)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.V84L (c.250G>T)

      LegacyVariant: p.V84L (c.463G>T)

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2236 https://www.ncbi.nlm.nih.gov/clinvar/variation/2236/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transversion

      CivicName: V84L (c.250G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline AssumedRefSeq:AF010238.1 DiseaseEntity:VHL Familial DiseaseEntity:pheochromocytoma DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:hemangioblastoma cDNAposition:250 ProteinPosition:84 AminoAcidChange:VALtoLEU ClinVarID:2236 ClinVarID:Yes MutationType:missense_variant;transversion CivicName:V84L(c.250G>T) inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    pubmed-ncbi-nlm-nih-gov.proxy1.lib.uwo.ca/9830390/
  82. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Germ‐line Mutation Analysis in Patients with von Hippel‐Lindau Disease in Japan: An Extended Study of 77 Families
    1
    1. ClingenBaseline 28 Oct 2026

      GroupID: 45

      DiseaseAssertion: VHL

      GroupSize: 2

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: Japanese

      GroupAgeRange: N/A

      GroupInfo: 2 individuals from a single family (ID 45).

      GroupPresentingHPOs: HP:0002666; HP:0005584 (Pheochromocytoma, Renal cell carcinoma)

      GroupHPOFreeText: Pheochromocytoma (1/2) and renal cell carcinoma (2/2).

      GroupNotHPOs: HP:0009711; HP:0001732; HP:0010797 (Retinal capillary hemangioma, Abnormality of the pancreas, Hemangioblastoma)

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: 8634692

      SupplementalData: N/A

      Variant: p.T157I (c.470C>T)

      LegacyVariant: c.683C>T

      CaseProblemVariantFreeText: N/A

      ClinVarID: 223223, https://www.ncbi.nlm.nih.gov/clinvar/variation/223223/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: T157I (c.470C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Japanese DiseaseEntity:VHL DiseaseEntity:renalcellcarcinoma DiseaseEntity:pheochromocytoma Mutation:Germline RefSeq:AF010238.1 cDNAposition:470 ProteinPosition:157 AminoAcidChange:THRtoILE ClinVarID:223223 ClinVarID:Yes MutationType:missense_variant;transition CivicName:T157I(c.470C>T) Familial FamilyCohort inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/10761708/
  83. nyaspubs-onlinelibrary-wiley-com.uhn.idm.oclc.org nyaspubs-onlinelibrary-wiley-com.uhn.idm.oclc.org
    von Hippel-Lindau gene mutation in non-syndromic familial pheochromocytomas
    1
    1. ClingenBaseline 27 Oct 2026
      Arg167Trp (712C-T)

      PatientID: (proband)

      KindredID: 4

      Case: M, Age unknown, Chinese

      DiseaseAssertion: pheochromocytoma 
FamilyInfo: There is a history of non-syndromic familial pheochromocytoma in this patient’s family history as well as a confirmed presence of this same germline mutation in their family. It is not perfectly clear which pedigree belongs to this family.

      CasePresentingHPOs: HP:0002666 (pheochromocytoma)

      CaseHPOFreeText: non-syndromic pheochromocytoma

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: No clinical manifestations of hereditary syndromes, including MEN2A, MEN2B, VHL, and NF1 were found

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: p.R167W (c.712C>T)

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Chinese DiseaseEntity:pheochromocytoma Familial FamilyPedigree CivicName:R167W(c.499C>T) cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP MutationType:missense_variant;transition Mutation:Germline AssumedRefSeq:AF010238.1 ClinVarID:2218 ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    nyaspubs-onlinelibrary-wiley-com.uhn.idm.oclc.org/doi/full/10.1196/annals.1353.022
  84. onlinelibrary.wiley.com onlinelibrary.wiley.com
    Genetic characterization and structural analysis of VHL Spanish families to define genotype–phenotype correlations
    2
    1. ClingenBaseline 27 Oct 2026

      GroupID/ KindredID: F9

      Case: Sex unknown, 20Y0M, Spanish

      DiseaseAssertion: assumed VHL

      FamilyInfo: None. Microsatellites were used to exclude nonpaternity, and the de novo character of the mutation was demonstrated in this patient. Paper says its confirmed however only discuss nonpaternity.

      CasePresentingHPOs: HP:0009711; HP:0006880; HP:0001737 (retinal capillary hemangioma, cerebellar hemangioblastoma, pancreatic cysts)

      CaseHPOFreeText: Cerebellar hemangioblastoma was found with multiple lesions. Age of onset is 20Y0M.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R161* (c.481C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 2217 https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: R161* (c.481C>T)

      MultipleGeneVariants: N/A

      Mutation:Germline Ethnicity:Spanish DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma RefSeq:AF010238.1 CivicName:R161*(c.481C>T) cDNAposition:481 ProteinPosition:161 AminoAcidChange:ARGtoTER MutationType:stop_gained ClinVarID:2217 ClinVarID:Yes ExperimentalAssay NonFamilial InheritancePattern:DeNovoAssertion inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 27 Oct 2026

      GroupID/ KindredID: F64

      Case: Sex unknown, 24Y0M, Spanish

      DiseaseAssertion: assumed VHL

      FamilyInfo: None

      CasePresentingHPOs: HP:0009711; HP:0002666; HP:0001737 (retinal capillary hemangioma, pheochromocytoma, clear cell renal cell carcinoma, pancreatic cysts)

      CaseHPOFreeText: Bilateral pheo was found. Age of onset is 24Y0M.

      CaseNotHPOs: HP:0006770; HP:0000107; HP:0006880 (clear cell renal cell carcinoma, renal cysts, cerebellar hemangioblastoma)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218 https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954 https://gnomad.broadinstitute.org/variant/3-10191506-C-T

      VariantEvidence: N/A

      MutationType: missense_variant; transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      Mutation:Germline InheritancePattern:AutosomalDominant Ethnicity:Spanish DiseaseEntity:VHL RefSeq:AF010238.1 DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:pancreaticcysts DiseaseEntity:pheochromocytoma DiseaseEntity:clearcellrenalcellcarcinoma ClinVarID:2218 ClinVarID:Yes CivicName:R167W(c.499C>T) cDNAposition:499 AminoAcidChange:ARGtoTRP ProteinPosition:167 MutationType:missense_variant;transition NoFamilyInfo ExperimentalAssay inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    onlinelibrary.wiley.com/doi/abs/10.1002/humu.10309
  85. onlinelibrary.wiley.com onlinelibrary.wiley.com
    Germline mutations detected in the von Hippel-Lindau disease tumor suppressor gene by southern blot and direct genomic DNA sequencing
    1
    1. ClingenBaseline 27 Oct 2026

      GroupID/ KindredID: 5

      DiseaseAssertion: VHL

      GroupSize: 2

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: Swedish

      GroupAgeRange: N/A

      GroupInfo: 2 patients grouped under family 5 were found in this Swedish VHL family

      GroupPresentingHPOs: HP:0005584; HP:0009711; HP:0010797 (renal cell carcinoma; retinal capillary hemangioma; hemangioblastoma)

      GroupHPOFreeText: Both (2/2) had renal cell carcinoma, and retinal capillary hemangioma; only 1/2 had hemangioblastoma.

      GroupNotHPOs: HP:0002666 (pheochromocytoma)

      GroupNotHPOFreeText: neither patient had pheochromocytoma

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.C162F (c.485G>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 43604 https://www.ncbi.nlm.nih.gov/clinvar/variation/43604/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transversion

      CivicName: C162F (c.485G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Swedish DiseaseEntity:VHL DiseaseEntity:renalcellcarcinoma DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:hemangioblastoma Mutation:Germline RefSeq:AF010238.1 CivicName:C162F(c.485G>T) cDNAposition:485 ProteinPosition:162 AminoAcidChange:CYStoPHE MutationType:missense_variant;transversion ClinVarID:43604 ClinVarID:Yes Familial FamilyCohort inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    onlinelibrary.wiley.com/doi/10.1002/humu.1380110111
  86. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Polyglobulia in patients with hemangioblastomas is related to tumor size but not to serum erythropoietin
    1
    1. ClingenBaseline 27 Oct 2026
      17m4717.5n18.3↑694 C/T–5.3

      PatientID: 17

      KindredID: 17

      Case: M, 47Y0M, Ethnicity Unknown

      DiseaseAssertion: Assumed VHL

      FamilyInfo: No details on family information.

      CasePresentingHPOs: HP:0010797 (hemangioblastoma)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R161* (c.481C>T)

      LegacyVariant: c.694C>T

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2217, https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: R161* (c.481C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline MutationType:stop_gained AssumedRefSeq:AF010238.1 CivicName:R161*(c.481C>T) cDNAPosition:481 ProteinPosition:161 AminoAcidChange:ARGtoTER ClinVarID:Yes ClinVarID:2217 NoFamilyInfo DiseaseEntity:hemangioblastoma inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC6131788/
  87. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Cryptic von Hippel-Lindau disease: germline mutations in patients with haemangioblastoma only
    1
    1. ClingenBaseline 27 Oct 2026
      A germline VHL mutation was detected in a 44 year old woman with a solitary cerebellar HAB,

      PatientID: D24

      KindredID: 1

      Case: F, 47Y0M, ethnicity unknown

      DiseaseAssertion: cerebellar hemangioblastoma

      FamilyInfo: DNA analysis of other close relatives showed that four clinically unaffected first and second degree relatives (aged 17-77 years) were also carriers of a P81S germline mutation. See Figure 3 for pedigree.

      CasePresentingHPOs: HP:0006880 (cerebellar hemangioblastoma)

      CaseHPOFreeText: patient had a single cerebellar HAB

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: 8956040; 9829911; 8634692; 17661816 (mentioned as a group)

      SupplementalData: N/A

      Variant: p.P81S (c.241C>T)

      LegacyVariant: p.P81S (c.454C>T)

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2233 https://www.ncbi.nlm.nih.gov/clinvar/variation/2233/

      CAID: N/A

      gnomAD: 0.0002179 https://gnomad.broadinstitute.org/variant/3-10183772-C-T

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: P81S (c.241C>T)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL InheritancePattern:AutosomalDominant DiseaseEntity:cerebellarhemangioblastoma Mutation:Germline RefSeq:AF010238.1 CivicName:P81S(c.241C>T) cDNAposition:241 ProteinPosition:81 AminoAcidChange:PROtoSER MutationType:missense_variant;transition ClinVarID:2233 ClinVarID:Yes Familial FamilyPedigree inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC1734505/
  88. academic.oup.com academic.oup.com
    VHL mutation analysis in patients with isolated central nervous system haemangioblastoma
    1
    1. ClingenBaseline 27 Oct 2026
      B5 CHB 39 c.811C → T, R200W No 6 y 3 m Nil 2 FDRs mutation positive

      PatientID: B5

      KindredID: 5

      Case: Sex Unknown, 39Y0M, Ethnicity Unknown

      DiseaseAssertion: cerebellar hemangioblastoma

      FamilyInfo: Two first degree relatives were found to have the same mutation in the VHL gene, both had no features of VHL disease at 28 and 38 years old

      CasePresentingHPOs: HP:0006880 (cerebellar hemangioblastoma)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: no other clinical features were found after the cerebellar hemangioblastoma during 6 years and 3 month follow-up

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R200W (c.598C>T)

      LegacyVariant: p.R200W (c.811C>T)

      ClinVarID: 2232 (https://www.ncbi.nlm.nih.gov/clinvar/variation/2232/)

      CAID: N/A

      gnomAD: 0.0002016 (https://gnomad.broadinstitute.org/variant/3-10191605-C-T)

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R200W(c.598C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:cerebellarhemangioblastoma Mutation:Germline cDNAposition:598 ProteinPosition:200 AminoAcidChange:ARGtoTRP ClinVarID:2232 MutationType:missense_variant;transition CivicName:R200W(c.598C>T) RefSeq:AF010238.1 AgeOfPresentation:cerebellarhemangioblastoma:39 ClinVarID:Yes Familial inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    academic.oup.com/brain/article/130/3/836/278946
  89. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Molecular diagnosis of von Hippel-Lindau disease in a kindred with a predominance of familial phaeochromocytoma
    2
    1. ClingenBaseline 27 Oct 2026
      Patients: Two generations of a family consisting of 15 individuals were studied.

      PatientID: II:1

      KindredID: 1

      Case: M, 49Y0M, Spanish

      DiseaseAssertion: pheochromocytoma

      FamilyInfo: Spanish family of 15 members studied, over 2 generations. 6 members had VHL presentations, 1 was a carrier, and 4 others had the mutation, while 2 were not sequenced. This patient’s 3 children showed VHL phenotypes, and his sister and 2 nieces presented with the VHL mutation.

      CasePresentingHPOs: HP:0002666 (pheochromocytoma)

      CaseHPOFreeText: first studied at 45Y, the patient had bilateral accumulation of pheo tumors, right: 9cm and left: 2cm

      CaseNotHPOs: HP:0006880; HP:0009711 (cerebellar hemangioblastoma, retinal capillary hemangioma)

      CaseNotHPOFreeText: Brain MRI and CT-scans were normal, and no signs of retinal angiomas were present.

      CasePreviousTesting: RET

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: p.R238T, C>T

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Spanish DiseaseEntity:pheochromocytoma AgeOfPresentation:pheochromocytoma:45 Mutation:Germline AssumedRefSeq:AF010238.1 Familial FamilyPedigree CivicName:R167W(c.499C>T) cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP MutationType:missense_variant;transition ClinVarID:2218 ClinVarID:Yes PreviousTesting:RET inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 27 Oct 2026
      Patients: Two generations of a family consisting of 15 individuals were studied.

      PatientID: III:9

      KindredID: 1

      Case: F, 25Y, Spanish

      DiseaseAssertion: pheochromocytoma

      FamilyInfo: Spanish family of 15 members studied, over 2 generations. 6 members had VHL presentations, 1 was a carrier, and 4 others had the mutation, while 2 were not sequenced. This patient’s sister was a carrier, while her mother mother, uncle, and cousins were affected.

      CasePresentingHPOs: HP:0002666 (pheochromocytoma)

      CaseHPOFreeText: First studied at 19Y, she had a bilateral tumor accumulation (Right, 6cm and Left 4cm).

      CaseNotHPOs: HP:0006880; HP:0009711 (cerebellar hemangioblastoma, retinal capillary hemangioma)

      CaseNotHPOFreeText: Brain MRI and CT-scans were normal, and no signs of retinal angiomas were present.

      CasePreviousTesting: RET

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      LegacyVariant: p.R238T, C>T

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Spanish AgeOfPresentation:pheochromocytoma:19 DiseaseEntity:pheochromocytoma Mutation:Germline AssumedRefSeq:AF010238.1 Familial FamilyPedigree ProteinPosition:167 CivicName:R167W(c.499C>T) cDNAposition:499 AminoAcidChange:ARGtoTRP MutationType:missense_variant;transition ClinVarID:2218 ClinVarID:Yes PreviousTesting:RET inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/9156047/
  90. academic.oup.com academic.oup.com
    Familial pheochromocytoma associated with a novel mutation in the von Hippel-Lindau gene
    1
    1. ClingenBaseline 27 Oct 2026
      709 G-->T transversion present in all affected subjects and in four presymptomatic children.

      PatientID: II:7

      KindredID: 1

      Case: M, Age Unknown, Jewish

      DiseaseAssertion: VHL

      FamilyInfo: This kindred of Jewish-Kurdish origin consisted of 3 generations of 25 members. 7 were clinically affected subjects with pheochromocytoma (5 of which had the confirmed mutation - I:1, II:2, II:4, II:7 and II:9, as the other 2, II:5 and II:10 were said to have passed due to complications of the disease - prior to any genetic testing), and 4 others were carriers, or pre-symptomatic (III:1, III:3, III:7 and III:12). Subject 11:7 developed a cerebellar hemangioblastoma 25 yr after his initial diagnosis of pheochromocytoma, leading to the clinical diagnosis of VHL in the kindred.

      CasePresentingHPOs: HP:0002666; HP:0006880; HP:0030074 (pheochromocytoma, cerebellar hemangiolastoma, chemodectoma)

      CaseHPOFreeText: patient had cerebellar HB at 25Y, after his initial diagnosis with bilateral pheochromocytoma, and then also extra-adrenal chromafin tumors (carotid body chemodectoma).

      CaseNotHPOs: HP:0005584 (renal cell carcinoma)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: 33471715

      SupplementalData: N/A

      Variant: p.V166F (c.496G>T)

      LegacyVariant: p.V166F (c.709G>T)

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2224, https://www.ncbi.nlm.nih.gov/clinvar/variation/2224/

      CAID: N/A

      VariantEvidence: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: V166F (c.496G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL Ethnicity:Jewish DiseaseEntity:chemodectoma DiseaseEntity:pheochromocytoma DiseaseEntity:cerebellarhemangioblastoma AgeOfPresentation:cerebellarhemangioblastoma:25 Mutation:Germline AssumedRefSeq:AF010238.1 Familial FamilyPedigree ClinVarID:2224 ClinVarID:Yes ProteinPosition:166 CivicName:V166F(c.496G>T) cDNAposition:496 MutationType:missense_variant;transversion AminoAcidChange:VALtoPHE inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    academic.oup.com/jcem/article/81/1/147/2649376
  91. erc.bioscientifica.com erc.bioscientifica.com
    Calculating optimal surveillance for detection of von Hippel–Lindau-related manifestations
    2
    1. ClingenBaseline 27 Oct 2026
      235 (CAG-TAG)1 (1)163HBr, HBc, HBsc, RCC, Cr

      GroupID: None

      Case: Sex Unknown, 63Y0M, Dutch

      DiseaseAssertion: VHL

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0009711, HP:0006880, HP:0009713, HP:0005584, HP:0000107 (Retinal capillary hemangioma, Cerebellar hemangioblastoma, Spinal hemangioblastoma, Renal cell carcinoma, Renal cyst)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: This cohort was published later in PMID 31087189

      SupplementalData: N/A

      Variant: p.R79C (c.235C>T)

      LegacyVariant: c.235 (CAG-TAG)

      CaseProblemVariantFreeText: written in the publication as c.235 (CAG-TAG), deduced to c.235C>T: p.Arg79Cys updated nomenclature

      ClinVarID: 161400 https://www.ncbi.nlm.nih.gov/clinvar/variation/161400/

      CAID: N/A

      gnomAD: 0.00002168, https://gnomad.broadinstitute.org/variant/3-10183766-C-T

      VariantEvidence: N/A

      MutationType: missense_variant; transition

      CivicName: R79C (c.235C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline Ethnicity:Dutch DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:cerebellarhemangioblastoma DiseaseEntity:spinalhemangioblastoma DiseaseEntity:renalcellcarcinoma DiseaseEntity:renalcyst ClinVarID:161400 ClinVarID:Yes NoFamilyInfo ProteinPosition:79 AminoAcidChange:ARGtoCYS cDNAposition:235 CivicName:R79C(c.235C>T) MutationType:missense_variant;transition inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 26 Oct 2026
       c.241C>T2 (2)2a/b47 (34–59)HBr, HBc, HBsc, RCC, pNET, Pheo, Cr

      GroupID:None

      DiseaseAssertion:VHL

      GroupSize: 2

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: Dutch

      GroupAgeRange: 34-59

      GroupInfo: 2 out of 82 individuals were grouped together based on all having the c.241C>T mutation. This group was classified as 2a/b meaning that it included de novo VHL mutation carriers or VHL mutation carriers having a family history with diagnosis of pheochromocytoma and other VHL related manifestations.

      GroupPresentingHPOs: HP:0009711, HP:0006880, HP:0009713, HP:0005584, HP:0030405, HP:0002666, HP:0000107 (Retinal capillary hemangioma, Cerebellar hemangioblastoma, Spinal hemangioblastoma, Renal cell carcinoma, Pancreatic endocrine tumor, Pheochromocytoma, Renal cyst)

      GroupHPOFreeText: It is unclear if both patients in this group had all of these presentations or if they were only affected by a subset.

      GroupNotHPOs: N/A

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.P81S (c.241C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 2233 https://www.ncbi.nlm.nih.gov/clinvar/variation/2233/

      CAID: N/A

      gnomAD: 0.0002179 https://gnomad.broadinstitute.org/variant/3-10183772-C-T

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: P81S (c.241C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline DiseaseEntity:VHL Ethnicity:Dutch NoFamilyInfo DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:cerebellarhemangioblastoma DiseaseEntity:spinalhemangioblastoma DiseaseEntity:renalcellcarcinoma DiseaseEntity:pancreaticendocrinetumor DiseaseEntity:pheochromocytoma DiseaseEntity:renalcyst CivicName:P81S(c.241C>T) cDNAposition:241 ProteinPosition:81 AminoAcidChange:PROtoSER AssumedRefSeq:NM_000551.3 ClinVarID:2233 MutationType:missense_variant;transition ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    erc.bioscientifica.com/view/journals/erc/21/1/63.xml
  92. www.endocrinepractice.org www.endocrinepractice.org
    VHL-Related Neuroendocrine Neoplasms And Beyond: An Israeli Specialized Center Real-Life Report
    3
    1. ClingenBaseline 26 Oct 2026
      In 1996, we described a 3 generation VHL 2A kindred with 11 mutation carriers. We aim to share our experience regarding the long-term follow-up of this family

      PatientID: 21

      KindredID: 1

      Case: F, 23Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: This patient was a member of family 1, where 14/32 total patients were diagnosed with VHL. One of which (I-32) was a mutational carrier with down syndrome. The other 13 patients had varying phenotypes, including adrenal pheochromocytoma, pancreatic endocrine tumors, liver and bone metastases, paraganglioma, cerebellar, spinal, and retinal hemangioblastomas, polycythemia, and chondrosarcoma. See Fig. 1 for family pedigree.

      CasePresentingHPOs: HP:0006748; HP:0009711 (adrenal pheochromocytoma; retinal capillary hemangioma)

      CaseHPOFreeText: Patient presented with his initial VHL-related clinical manifestations at 11Y0M. She had adrenal pheochromocytoma and retinal capillary hemangioma. She was diagnosed with VHL subtype 2A(see table 1).

      CaseNotHPOs: HP:0002668 (paraganglioma)

      CaseNotHPOFreeText: Patient does not have paraganglioma.

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.V166F (c.496G>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2224, https://www.ncbi.nlm.nih.gov/clinvar/variation/2224/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transversion

      CivicName: V166F (c.496G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline MutationType:missense_variant;transversion DiseaseEntity:VHL DiseaseEntity:adrenalpheochromocytoma DiseaseEntity:retinalcapillaryhemangioma CivicName:V166F(c.496G>T) cDNAPosition:496 ProteinPosition:166 AminoAcidChange:VALtoPHE RefSeq:NM_000551.3 Familial FamilyPedigree ClinVarID:2224 ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    2. ClingenBaseline 26 Oct 2026
      In 1996, we described a 3 generation VHL 2A kindred with 11 mutation carriers. We aim to share our experience regarding the long-term follow-up of this family

      PatientID: 3

      KindredID: 1

      Case: M, 55Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: This patient was a member of family 1, where 14/32 total patients were diagnosed with VHL. One of which (I-32) was a mutational carrier with down syndrome. The other 13 patients had varying phenotypes, including adrenal pheochromocytoma, pancreatic endocrine tumors, liver and bone metastases, paraganglioma, cerebellar, spinal, and retinal hemangioblastomas, polycythemia, and chondrosarcoma. See Fig. 1 for family pedigree.

      CasePresentingHPOs: HP:0006748; HP:0002668; HP:0030405; HP:0009713; HP:0006880; HP:0001901 (adrenal pheochromocytoma; paraganglioma; pancreatic endocrine tumor; spinal hemagnioblastoma, cerebellar hemagnioblastoma; polycythemia)

      CaseHPOFreeText: Patient presented with his initial VHL-related clinical manifestations at 7Y0M. He was found to have adrenal pheochromocytoma; paraganglioma, pancreatic endocrine tumor, spinal and cerebellar hemagnioblastoma, and polycythemia (see table 1). Patient was diagnosed with VHL subtype 2A at 54Y0M.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: 8550742

      SupplementalData: N/A

      Variant: p.V166F (c.496G>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2224, https://www.ncbi.nlm.nih.gov/clinvar/variation/2224/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transversion

      CivicName: V166F (c.496G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline MutationType:missense_variant;transversion DiseaseEntity:VHL DiseaseEntity:adrenalpheochromocytoma DiseaseEntity:paraganglioma DiseaseEntity:pancreaticendocrinetumor DiseaseEntity:spinalhemangioblastoma DiseaseEntity:cerebellarhemangioblastoma DiseaseEntity:polycythemia CivicName:V166F(c.496G>T) cDNAPosition:496 ProteinPosition:166 AminoAcidChange:VALtoPHE RefSeq:NM_000551.3 ClinVarID:2224 ClinVarID:Yes Familial AgeOfPresentation:VHL:7 FamilyPedigree inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    3. ClingenBaseline 23 Oct 2026
      In 1996, we described a 3 generation VHL 2A kindred with 11 mutation carriers. We aim to share our experience regarding the long-term follow-up of this family

      PatientID: 26

      KindredID: 1

      Case: M, 16Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: This patient was a member of family 1, where 14/32 total patients were diagnosed with VHL. One of which (I-32) was a mutational carrier with down syndrome. The other 13 patients had varying phenotypes, including adrenal pheochromocytoma, pancreatic endocrine tumors, liver and bone metastases, paraganglioma, cerebellar, spinal, and retinal hemangioblastomas, polycythemia, and chondrosarcoma. See Fig. 1 for family pedigree.

      CasePresentingHPOs: HP:0006748 (adrenal pheochromocytoma)

      CaseHPOFreeText: Patient presented with his initial VHL-related clinical manifestations at 16Y0M. She had adrenal pheochromocytoma and diagnosed with VHL subtype 2A (see table 1).

      CaseNotHPOs: HP:0002668 (paraganglioma)

      CaseNotHPOFreeText: Patient does not have paraganglioma.

      CasePreviousTesting: N/A

      PreviouslyPublished: 8550742

      SupplementalData: N/A

      Variant: p.V166F (c.496G>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2224, https://www.ncbi.nlm.nih.gov/clinvar/variation/2224/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transversion

      CivicName: V166F (c.496G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline MutationType:missense_variant;transversion DiseaseEntity:VHL DiseaseEntity:adrenalpheochromocytoma AgeOfPresentation:VHL:16 AgeOfPresentation:adrenalpheochromocytoma:16 CivicName:V166F(c.496G>T) cDNAPosition:496 ProteinPosition:166 AminoAcidChange:VALtoPHE RefSeq:NM_000551.3 ClinVarID:Yes ClinVarID:2224 Familial FamilyPedigree inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    endocrinepractice.org/article/S1530-891X(20)48218-7/fulltext
  93. link-springer-com.proxy1.lib.uwo.ca link-springer-com.proxy1.lib.uwo.ca
    A Novel Von Hippel–Lindau Case With Germline Mutation at Codon 167 (CGG to TGG) Having Endocrine Microadenomatosis of the Pancreas
    1
    1. ClingenBaseline 26 Oct 2026
      A 40-year-old woman was admitted to our hospital for further evaluation of a left RCC that had been found during a routine checkup. Computed tomography of the abdomen showed multiple, small tumors (≤10 mm in diameter) in the head of the pancreas as well as a left renal mass, measuring 8×7×6 cm in size (Fig. 1a). Selective abdominal angiography (via the celiac and supramesenteric arteries) disclosed numerous small tumor stains in the pancreatic head (Fig. 1b). Multiple pancreatic metastases from the left RCC were first suspected. Pancreatic microadenomatosis of MEN1 syndrome was also suggested, but no other lesions related to this syndrome (such as pituitary adenoma, parathyroid adenoma, or adrenocortical tumor) were observed. This patient had no clinical symptoms of inappropriate pancreatic hormone secretions such as insulin, glucagon, and gastrin.

      PatientID: None

      KindredID: 1

      Case: F, 43Y0M, Ethnicity Unknown

      DiseaseAssertion: Assumed VHL

      FamilyInfo: None

      CasePresentingHPOs: HP:0006770, HP:0030405, HP:0004510 (clear cell renal cell carcinoma, pancreatic endocrine tumour, Pancreatic islet-cell hyperplasia)

      CaseHPOFreeText: At age 40 the patient presented with left sided clear cell renal cell carcinoma, islet cell hyperplasia, and pancreatic endocrine tumour. 46 months later the patient has no evidence of recurrence.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 2218 https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954 https://gnomad.broadinstitute.org/variant/3-10191506-C-T

      VariantEvidence: Both the hyperplastic islet cells and pancreatic microadenomas stained negatively for marker upon immunohistochemical testing for hypoxia-inducible factor (HIF)-1α.

      MutationType: missense_variant; transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline AssumedRefSeq:NM_000551.3 DiseaseEntity:AssumedVHL NonFamilial DiseaseEntity:clearcellrenalcellcarcinoma AgeOfPresentation:clearcellrenalcellcarcinoma:40 DiseaseEntity:pancreaticendocrinetumor AgeOfPresentation:pancreaticendocrinetumor:40 DiseaseEntity:Pancreaticislet-cellhyperplasia AgeOfPresentation:Pancreaticislet-cellhyperplasia:40 CivicName:R167W(c.499C>T) cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP ClinVarID:2218 ClinVarID:Yes MutationType:missense_variant;transition inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    link-springer-com.proxy1.lib.uwo.ca/article/10.1007/s10620-007-9780-x
  94. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Clinical and genetic characterization of pheochromocytoma in von Hippel-Lindau families: comparison with sporadic pheochromocytoma gives insight into natural history of pheochromocytoma
    2
    1. ClingenBaseline 26 Oct 2026

      KindredID: 4885

      Case: Sex Unknown, Age Unknown, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0002666; HP:0005584; HP:0010797 (Pheochromocytoma, Renal cell carcinoma, Hemangioblastoma)

      CaseHPOFreeText: The patient was also described to have cysts but the type or location was not specified.

      CaseNotHPOs: HP:0009711; HP:0030405 (Retinal capillary hemangioma, Pancreatic endocrine tumor)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R161* (c.481C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: p.R161* (c.694C>T)

      ClinVarID: 2217, https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: Variant reported as 694, C to T (Arg to stop), assumed to be reported in legacy nomenclature (AF010238.1) and mapped to c.481C>T, p.Arg161* (NM_000551.3).

      MutationType: stop_gained; missense_variant;transition

      CivicName: R161* (c.481C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:pheochromocytoma DiseaseEntity:hemangioblastoma DiseaseEntity:renalcellcarcinoma Mutation:Germline AssumedRefSeq:AF010238.1 cDNAposition:481 ProteinPosition:161 AminoAcidChange:ARGtoTER ClinVarID:2217 ClinVarID:Yes MutationType:missense_variant;transition MutationType:stop_gained CivicName:R161*(c.481C>T) NoFamilyInfo inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    2. ClingenBaseline 24 Oct 2026

      KindredID: 1112

      Case: Sex Unknown, Age Unknown, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0002666; HP:0010797; HP:0009711 (Pheochromocytoma, Hemangioblastoma, Retinal capillary hemangioma)

      CaseHPOFreeText: N/A

      CaseNotHPOs: HP:0030405; HP:0005584 (Pancreatic endocrine tumor, Renal cell carcinoma)

      CaseNotHPOFreeText: The patient had no cysts (type or location was not specified).

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R161* (c.481C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: p.R161* (c.694C>T)

      ClinVarID: 2217, https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: Variant reported as 694, C to T (Arg to stop), assumed to be reported in legacy nomenclature (AF010238.1) and mapped to c.481C>T, p.Arg161* (NM_000551.3).

      MutationType: stop_gained; missense_variant;transition

      CivicName: R161* (c.481C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:pheochromocytoma DiseaseEntity:hemangioblastoma Mutation:Germline AssumedRefSeq:AF010238.1 cDNAposition:481 ProteinPosition:161 AminoAcidChange:ARGtoTER ClinVarID:2217 ClinVarID:Yes MutationType:missense_variant;transition MutationType:stop_gained CivicName:R161*(c.481C>T) NoFamilyInfo DiseaseEntity:retinalcapillaryhemangioma inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/10458336/
  95. journals.lww.com journals.lww.com
    Pancreatic endocrine microadenomatosis in patients with von Hippel-Lindau disease: characterization by VHL/HIF pathway proteins expression
    1
    1. ClingenBaseline 26 Oct 2026
      Eighteen VHL patients who underwent pancreatectomy for one or several endocrine tumors at Beaujon hospital from 1997 to 2008 were retrieved from the file of VHL patients (Table 1).

      PatientID: 2

      KindredID: 2

      Case: F, 28Y0M, Ethnicity unknown

      DiseaseAssertion: pancreatic endocrine tumor

      FamilyInfo: None

      CasePresentingHPOs: HP:0030405 (pancreatic endocrine tumor)

      CaseHPOFreeText: See Table 1 for more information

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 2218 https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: CA020450 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.499C%3ET

      gnomAD: 0.000007954 https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_variant; transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:pancreaticendocrinetumor Mutation:Germline AssumedRefSeq:NM_000551.3 CivicName:R167W(c.499C>T) cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTER ClinVarID:2218 MutationType:missense_variant;transition CAID:CA020450 NoFamilyInfo ClinVarID:Yes InheritancePattern:AutosomalDominant ExperimentalAssay inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    journals.lww.com/ajsp/fulltext/2009/05000/pancreatic_endocrine_microadenomatosis_in_patients.9.aspx
  96. jmg-bmj-com.uhn.idm.oclc.org jmg-bmj-com.uhn.idm.oclc.org
    Evidence for genetic anticipation in vonHippel-Lindau syndrome
    3
    1. ClingenBaseline 26 Oct 2026

      PatientID: 83 (Cousin)

      KindredID: 18

      Case: F, 50Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: 11 members of this family tested positive for the c.712C>T/c.499C>T germline variant of the VHL gene. 14 members of this family were assumed to carry this variant due to family history/personal medical history. Members of this family range from asymptomatic to multi-organ involvement (pheochromocytoma, pancreatic and renal cysts/tumors and hemangioblastomas). The family was previously reported in PMID 3942913.

      CasePresentingHPOs: HP:0010797; HP:0009711; HP:0001732 (Hemangioblastoma, Retinal capillary hemangioma, Abnormality of the pancreas)

      CaseHPOFreeText: This patient presented with CNS hemangioblastoma (25Y), retinal angioma (16Y) and pancreatic tumors or cysts (undefined) (22Y).

      CaseNotHPOs: HP:0005584; HP:0000077; HP:0002666 (Renal cell carcinoma, Abnormality of the kidney, Pheochromocytoma)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: 3942913 (some members of this family are previously reported (phenotypes only) but unable to match patients across papers with confidence)

      SupplementalData: Supplementary Table 1.

      Variant: p.R167W (c.499C>T)

      LegacyVariant: c.712C>T

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: A point mutation (c.712C>T) was found. Being that this variant is out of bound with respect to the NM_000551.3 reference sequence, it was concluded that this variant is noted in the Latif et al. (1993) reference and was translated to c.499C>T (NM_000551.3).

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:hemangioblastoma DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:abnormalityofthepancreas AgeOfPresentation:hemangioblastoma:25 AgeOfPresentation:retinalcapillaryhemangioma:16 AgeOfPresentation:abnormalityofthepancreas:22 Mutation:Germline AssumedRefSeq:AF010238.1 cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP ClinVarID:2218 ClinVarID:Yes MutationType:missense_variant;transition CivicName:R167W(c.499C>T) Familial inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    2. ClingenBaseline 25 Oct 2026

      PatientID: 3 (Father)

      KindredID: 10

      Case: M, 43Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: 2 members of this family presented with the c.712C>T/c.499C>T germline variant of the VHL gene. ID 1 (Proband) was asymptomatic.

      CasePresentingHPOs: HP:0010797; HP:0005584; HP:0009711 (Hemangioblastoma, Renal cell carcinoma, Retinal capillary hemangioma)

      CaseHPOFreeText: This patient presented with CNS hemangioblastoma (32Y), retinal angioma (33Y) and renal cell carcinoma (33Y).

      CaseNotHPOs: HP:0000077; HP:0002666; HP:0001732 (Abnormality of the kidney, Pheochromocytoma, Abnormality of the pancreas)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: Supplementary Table 1.

      Variant: p.R167W (c.499C>T)

      LegacyVariant: c.712C>T

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: A point mutation (c.712C>T) was found. Being that this variant is out of bound with respect to the NM_000551.3 reference sequence, it was concluded that this variant is noted in the Latif et al. (1993) reference and was translated to c.499C>T (NM_000551.3).

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:hemangioblastoma DiseaseEntity:renalcellcarcinoma DiseaseEntity:retinalcapillaryhemangioma AgeOfPresentation:hemangioblastoma:32 AgeOfPresentation:renalcellcarcinoma:33 AgeOfPresentation:retinalcapillaryhemangioma:33 Mutation:Germline AssumedRefSeq:AF010238.1 cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP ClinVarID:2218 ClinVarID:Yes MutationType:missense_variant;transition CivicName:R167W(c.499C>T) Familial inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    3. ClingenBaseline 23 Oct 2026

      PatientID: 49 (Cousin)

      KindredID: 18

      Case: F, 62Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: 11 members of this family tested positive for the c.712C>T/c.499C>T germline variant of the VHL gene. 14 members of this family were assumed to carry this variant due to family history/personal medical history. Members of this family range from asymptomatic to multi-organ involvement (pheochromocytoma, pancreatic and renal cysts/tumors and hemangioblastomas). The family was previously reported in PMID 3942913.

      CasePresentingHPOs: HP:0002666; HP:0009711; HP:0005584; HP:0010797 (Pheochromocytoma, Retinal capillary hemangioma, Renal cell carcinoma, Hemangioblastoma)

      CaseHPOFreeText: This patient presented with retinal angioma (18Y) and pheochromocytoma (20Y). Age of diagnosis of CNS hemangioblastoma and renal cell carcinoma is unknown.

      CaseNotHPOs: HP:0000077; HP:0001732 (Abnormality of the kidney, Abnormality of the pancreas)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: 3942913 (some members of this family are previously reported (phenotypes only) but unable to match patients across papers with confidence)

      SupplementalData: Supplementary Table 1.

      Variant: p.R167W (c.499C>T)

      LegacyVariant: c.712C>T

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: A point mutation (c.712C>T) was found. Being that this variant is out of bound with respect to the NM_000551.3 reference sequence, it was concluded that this variant is noted in the Latif et al. (1993) reference and was translated to c.499C>T (NM_000551.3).

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:pheochromocytoma AgeOfPresentation:retinalcapillaryhemangioma:18 AgeOfPresentation:pheochromocytoma:20 Mutation:Germline AssumedRefSeq:AF010238.1 cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP ClinVarID:2218 ClinVarID:Yes MutationType:missense_variant;transition CivicName:R167W(c.499C>T) Familial DiseaseEntity:hemangioblastoma DiseaseEntity:renalcellcarcinoma inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    jmg-bmj-com.uhn.idm.oclc.org/content/55/6/395
  97. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Mutations in the VHL tumor suppressor gene and associated lesions in families with von Hippel-Lindau disease from central Europe
    3
    1. ClingenBaseline 26 Oct 2026

      GroupID/ KindredID: VHL 56

      DiseaseAssertion: assumed VHL

      GroupSize: 2

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: German

      GroupAgeRange: N/A

      GroupInfo: 2 patients with the given mutation belonging to VHL family 56

      GroupPresentingHPOs: HP:0009711; HP:0010797 (retinal capillary hemangioma, hemangioblastoma)

      GroupHPOFreeText: both (2) patients have retinal angioma and hemangioblastomas

      GroupNotHPOs: N/A

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.Q195* (c.583C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: p.Q195* (c.796C>T)

      ClinVarID: 428794 https://www.ncbi.nlm.nih.gov/clinvar/variation/428794/

      CAID: CA70052558 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.583C%3ET

      gnomAD: N/A

      VariantEvidence: allele-specific oligonucleotide (ASO) probes and hybridization conditions confirmed

      MutationType: missense_variant; transition

      CivicName: Q195* (c.583C>T)

      MultipleGeneVariants: N/A

      Ethnicity:German Mutation:Germline DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:hemangioblastoma AssumedRefSeq:AF010238.1 MutationType:missense_variant;transition Familial CivicName:Q195*(c.583C>T) cDNAposition:583 ProteinPosition:195 AminoAcidChange:GLNtoTER InheritancePattern:AutosomalDominant ClinVarID:Yes ClinVarID:428794 CAID:CA70052558 FamilyCohort inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
    2. ClingenBaseline 25 Oct 2026

      GroupID/ KindredID: VHL 65

      Case: Sex unknown, Age unknown, Iranian

      DiseaseAssertion: assumed VHL

      FamilyInfo: One patient with the given mutation is stated to belong to VHL family 65

      CasePresentingHPOs: HP:0009711; HP:0010797; HP:0001737; HP:0000107; HP:0005584; HP:0008261 (retinal capillary hemangioma, hemangioblastoma, pancreatic cysts, renal cyst, renal cell carcinoma, pancreatic islet cell adenoma)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.Q164* (c.490C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: p.Q164* (c.703C>T)

      ClinVarID: 223228 https://www.ncbi.nlm.nih.gov/clinvar/variation/223228/

      CAID: CA357060 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.490C%3ET

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: Q164* (c.490C>T)

      MultipleGeneVariants: N/A

      Ethnicity:Iranian Mutation:Germline DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:hemangioblastoma DiseaseEntity:pancreaticcysts DiseaseEntity:renalcyst DiseaseEntity:renalcellcarcinoma DiseaseEntity:pancreaticisletcelladenoma DiseaseEntity:VHL Familial AminoAcidChange:GLNtoTER ProteinPosition:164 MutationType:stop_gained CivicName:Q164*(c.490C>T) cDNAposition:490 ClinVarID:223228 CAID:CA357060 ClinVarID:Yes InheritancePattern:AutosomalDominant inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
    3. ClingenBaseline 25 Oct 2026

      GroupID/ KindredID: VHL 55

      DiseaseAssertion: assumed VHL

      GroupSize: 2

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: German

      GroupAgeRange: N/A

      GroupInfo: 2 patients with the given mutation belonging to VHL family 55

      GroupPresentingHPOs: HP:0009711; HP:0010797 (retinal capillary hemangioma, hemangioblastoma)

      GroupHPOFreeText: Both (2) patients have retinal angiomas (retinal capillary hemangioma) and CNS hemangioblastomas

      GroupNotHPOs: N/A

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R113* (c.337C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: p.R113* (c.550C>T)

      ClinVarID: 220414 https://www.ncbi.nlm.nih.gov/clinvar/variation/220414/

      CAID: CA348491 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.337C%3ET

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: R113* (c.337C>T)

      MultipleGeneVariants: N/A

      CAID:CA348491 ClinVarID:220414 MutationType:stop_gained ProteinPosition:113 CivicName:R113*(c.337C>T) cDNAposition:337 Ethnicity:German Mutation:Germline AssumedRefSeq:AF010238.1 DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:hemangioblastoma DiseaseEntity:VHL Familial AminoAcidChange:ARGtoTER ClinVarID:Yes InheritancePattern:AutosomalDominant FamilyCohort inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/8707293/
  98. hccpjournal.biomedcentral.com hccpjournal.biomedcentral.com
    Mutations in the von hippel-lindau tumour suppressor gene in central nervous system hemangioblastomas
    1
    1. ClingenBaseline 26 Oct 2026
      481C>T Arg161X Germline mutation

      PatientID: 51

      KindredID: 51

      Case: Age, sex, ethnicity unknown

      DiseaseAssertion: hemangioblastoma

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0010797 (hemangioblastoma)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R161* (c.481C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 2217 https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: R161* (c.481C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline DiseaseEntity:hemangioblastoma AssumedRefSeq:NM_000551.3 ProteinPosition:161 CivicName:R161*(c.481C>T) cDNAposition:481 AminoAcidChange:ARGtoTER MutationType:stop_gained ClinVarID:2217 ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    hccpjournal.biomedcentral.com/article/10.1186/1897-4287-2-2-93/tables/1
  99. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Genotype-phenotype correlation in von Hippel-Lindau families with renal lesions
    2
    1. ClingenBaseline 26 Oct 2026

      GroupID: 1

      DiseaseAssertion: VHL

      GroupSize:14

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: French

      GroupAgeRange: N/A

      GroupInfo: 14 members of this family presented with the c.499C>T germline variant of the VHL gene. Members 296, 419, 295 and 414 had no renal involvement. Members 427, 318, 403 and 406 had unknown renal involvement. Members 402, 322, 403 and 1 had mild renal disease (RCC). Members 401 and 404 had moderate renal disease (RCC). Families were recruited from the French VHL Registry. Enrolment in the study required identification of the germline VHL mutation (currently 85% of the families included in the French VHL Registry) and available data regarding renal phenotype. A total of 126 families fulfilled these criteria.

      GroupPresentingHPOs: HP:0009726; HP:0005584 (Renal neoplasm, Renal cell carcinoma)

      GroupHPOFreeText: Mild renal disease (simple renal cyst, multicystic kidney[s], small lesion [less than 10 mm in size] of unknown significance, or small solid tumor without indication for surgical removal [less than 30 mm in size]). Moderate renal disease (less than five solid lesions requiring surgical treatment, either unilateral or bilateral).

      GroupNotHPOs: N/A

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: Paper states that this family is previously reported in PMID 12202531 and/or 9829912, where 15 individuals and 3 families respectively with this mutation are reported. It is unclear if one or both of these previously reported groups are the same as the current family. These previously reported individuals/families could alternatively correspond to family 23 or 50.

      SupplementalData: Phenotype and genotype information can be found in Supplementary Table S1.

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:French DiseaseEntity:VHL DiseaseEntity:renalneoplasm DiseaseEntity:renalcellcarcinoma Mutation:Germline RefSeq:NM_000551.3 cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP ClinVarID:2218 ClinVarID:Yes MutationType:missense_variant;transition CivicName:R167W(c.499C>T) Familial FamilyCohort SupplementalData inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    2. ClingenBaseline 23 Oct 2026

      GroupID: 49

      DiseaseAssertion: VHL

      GroupSize: 2

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: French

      GroupAgeRange: N/A

      GroupInfo: 2 members of this family presented with the c.496G>T germline variant of the VHL gene. Member 2046 had no renal involvement. Member 1258 presented with mild renal disease. Families were recruited from the French VHL Registry. Enrolment in the study required identification of the germline VHL mutation (currently 85% of the families included in the French VHL Registry) and available data regarding renal phenotype. A total of 126 families fulfilled these criteria.

      GroupPresentingHPOs: HP:0009726 (Renal neoplasm)

      GroupHPOFreeText: Mild renal disease (simple renal cyst, multicystic kidney[s], small lesion [less than 10 mm in size] of unknown significance, or small solid tumor without indication for surgical removal [less than 30 mm in size]).

      GroupNotHPOs: N/A

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: Paper states that this family is previously reported in PMID 12202531 and/or 9829912, where 2 and 1 individuals respectively with this mutation are reported. It is unclear if one or both of these previously reported groups are the same as the current family.

      SupplementalData: Phenotype and genotype information can be found in Supplementary Table S1.

      Variant: p.V166F (c.496G>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2224, https://www.ncbi.nlm.nih.gov/clinvar/variation/2224/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: V166F (c.496G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:French DiseaseEntity:VHL DiseaseEntity:renalneoplasm Mutation:Germline RefSeq:NM_000551.3 cDNAposition:496 ProteinPosition:166 AminoAcidChange:VALtoPHE ClinVarID:2224 ClinVarID:Yes MutationType:missense_variant;transversion CivicName:V166F(c.496G>T) Familial FamilyCohort SupplementalData inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/15300849/
  100. www.frontiersin.org www.frontiersin.org
    Frequent Mutations of VHL Gene and the Clinical Phenotypes in the Largest Chinese Cohort With Von Hippel–Lindau Disease
    2
    1. ClingenBaseline 26 Oct 2026
      c.269A > T p.Asn90Ile (group 8)

      GroupID: 8

      DiseaseAssertion: assumed VHL

      GroupSize: 15

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: Chinese

      GroupAgeRange: 36.9Y +/- 15.6Y

      GroupInfo: Clinical characteristics of 258 patients from 80 unrelated Chinese families were reported in this study. Grouped by the 21 mutations found, 3 families with 15 members total were described, and phenotypic information was given for this group.

      GroupPresentingHPOs: HP:0010797; HP:0009711; HP:0005584; HP:0001737; HP:0002666 (hemangioblastoma, retinal capillary hemangioma, renal cell carcinoma, pancreatic cysts, pheochromocytoma)

      GroupHPOFreeText: 10 of the 15 members presented with CNS hemangioblastoma (mean age of 29.9Y), 2/15 had retinal capillary hemangiomas at 23Y and 30Y, renal cell carcinoma in 4 members (at a mean age of 41.5Y), pancreatic cysts in 5 members (with a mean age of onset of 41.4Y), and 1 member with pheochromocytoma at 38Y

      GroupNotHPOs: HP:0009715 (papillary cystadenoma of the epididymis)

      GroupNotHPOFreeText: No patients were given with papillary cystadenoma of the epididymis

      GroupPreviousTesting: N/A

      PreviouslyPublished: 29330336; 28388566

      SupplementalData: N/A

      Variant: p.N90I (c.269A>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 223172 https://www.ncbi.nlm.nih.gov/clinvar/variation/223172/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: N90I (c.269A>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Chinese DiseaseEntity:hemangioblastoma DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:renalcellcarcinoma DiseaseEntity:pancreaticcysts DiseaseEntity:pheochromocytoma AgeOfPresentation:pheochromocytoma:38 Mutation:Germline AssumedRefSeq:NM_000551.3 ClinVarID:223172 ClinVarID:Yes CivicName:N90I(c.269A>T) cDNAposition:269 ProteinPosition:90 AminoAcidChange:ASNtoILE MutationType:missense_variant;transition Familial FamilyCohort AgeOfPresentation:retinalcapillaryhemangioma:23 AgeOfPresentation:renalcellcarcinoma:30 inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    2. ClingenBaseline 26 Oct 2026
      337

      GroupID: 10

      DiseaseAssertion: assumed VHL

      GroupSize: 6

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: Chinese

      GroupAgeRange: 47.0Y +/- 18.4Y

      GroupInfo: Clinical characteristics of 258 patients from 80 unrelated Chinese families were reported in this study. Grouped by the 21 mutations found, 2 families with 6 members total were described, and phenotypic information was given for this group.

      GroupPresentingHPOs: HP:0010797; HP:0009711; HP:0005584; HP:0001737; HP:0009715 (hemangioblastoma, retinal capillary hemangioma, renal cell carcinoma, pancreatic cysts, papillary cystadenoma of the epididymis)

      GroupHPOFreeText: 3 of the 6 members presented with CNS hemangioblastoma (mean age of 40.0Y), 3/6 had retinal capillary hemangiomas (at a mean age of 23Y), renal cell carcinoma in 3 members (at a mean age of 35.3Y), pancreatic cysts in 2 members (with age of onsets of 26 and 27Y), and 1 with a papillary cystadenoma of the epididymis genital system tumor (epididymis or broad ligament) (at age 18Y).

      GroupNotHPOs: HP:0002666 (pheochromocytoma)

      GroupNotHPOFreeText: no members were found with pheochromocytomas

      GroupPreviousTesting: N/A

      PreviouslyPublished: 29330336

      SupplementalData: N/A

      Variant: p.R113* (c.337C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 220414 https://www.ncbi.nlm.nih.gov/clinvar/variation/220414/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: R113* (c.337C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Chinese DiseaseEntity:hemangioblastoma DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:renalcellcarcinoma DiseaseEntity:pancreaticcysts DiseaseEntity:papillarycystadenomaoftheepididymis AgeOfPresentation:papillarycystadenomaoftheepididymis:18 Mutation:Germline AssumedRefSeq:NM_000551.3 ClinVarID:Yes ClinVarID:220414 MutationType:stop_gained ProteinPosition:113 cDNAposition:337 CivicName:R113*(c.337C>T) AminoAcidChange:ARGtoTER Familial FamilyCohort AgeOfPresentation:pancreaticcysts:26 AgeOfPresentation:pancreaticcysts:27 inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    frontiersin.org/articles/10.3389/fgene.2019.00867/full
  101. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Three novel germ-line VHL mutations in Hungarian von Hippel-Lindau patients, including a nonsense mutation in a fifteen-year-old boy with renal cell carcinoma
    1
    1. ClingenBaseline 26 Oct 2026
      The patient was heterozygous for the novel c.163 G > T (p.55GluX) amber nonsense mutation

      PatientID: 1

      KindredID: 1 (A)

      Case: M, 15Y0M, Hungarian

      DiseaseAssertion: VHL

      FamilyInfo: Both parents were healthy with no display of any mutations in the VHL gene, indicating a de novo mutation.

      CasePresentingHPOs: HP:0006770; HP:0009711 (clear cell renal cell carcinoma, retinal capillary hemangioma)

      CaseHPOFreeText: Patient developed bilateral retinal angioma (retinal capillary hemangioma) and had serious retinal detachment.

      CaseNotHPOs: HP:0010797; HP:0002666 (hemangioblastoma, pheochromocytoma)

      CaseNotHPOFreeText: MRI of the craniospinal axis could not detect any alterations. No deviation from normal values was observed in the laboratory test.

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.E55* (c.163G>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVar: N/A

      CAID: CA351748495 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.163G%3ET

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transversion

      CivicName: E55* (c.163G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:DeNovoAssertion Ethnicity:Hungarian DiseaseEntity:VHL DiseaseEntity:clearcellrenalcellcarcinoma DiseaseEntity:retinalcapillaryhemangioma AgeOfPresentation:retinalcapillaryhemangioma:15 AgeOfPresentation:clearcellrenalcellcarcinoma:15 Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:163 ProteinPosition:55 AminoAcidChange:GLUtoTER CivicName:E55*(c.163G>T) deNovoConfirmed CAID:CA351748495 MutationType:stop_gained ClinVarID:N/A inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/23298237/
  102. www-nature-com.proxy1.lib.uwo.ca www-nature-com.proxy1.lib.uwo.ca
    Integrated molecular analysis of clear-cell renal cell carcinoma
    2
    1. ClingenBaseline 26 Oct 2026

      PatientID: ccRCC-132

      KindredID: 132

      Case: M, 59Y0M, Ethnicity Unknown

      DiseaseAssertion: Clear Cell Renal Cell Carcinoma

      FamilyInfo: N/A

      CohortInfo: 240 ccRCC specimens.

      CasePresentingHPOs: HP:0006770 (clear cell renal cell carcinoma)

      CaseHPOFreeText:He was diagnosed with ccRCC at age 54.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: Supplementary table 1.

      Variant: c.464-1G>T

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 223221 https://www.ncbi.nlm.nih.gov/clinvar/variation/223221/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: splice_site_variant

      CivicName: Splice Site (c.464-1G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline AssumedRefSeq:NM_000551.3 DiseaseEntity:clearcellrenalcellcarcinoma AgeOfPresentation:clearcellrenalcellcarcinoma:54 NoFamilyInfo SupplementalData CivicName:SpliceSite(c.464-1G>T) cDNAposition:464 MutationType:splice_site_variant ClinVarID:223221 ClinVarID:Yes AminoAcidChange:N/A ProteinPosition:N/A inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    2. ClingenBaseline 23 Oct 2026

      PatientID: ccRCC-159

      KindredID: 159

      Case: M, 59Y0M, Ethnicity Unknown

      DiseaseAssertion: Clear Cell Renal Cell Carcinoma

      FamilyInfo: N/A

      CohortInfo: 240 ccRCC specimens.

      CasePresentingHPOs: HP:0006770 (clear cell renal cell carcinoma)

      CaseHPOFreeText:He was diagnosed with ccRCC at age 56.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: Supplementary table 1.

      Variant: c.464-1G>T

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 223221 https://www.ncbi.nlm.nih.gov/clinvar/variation/223221/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: splice_site_variant

      CivicName: Splice Site (c.464-1G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline AssumedRefSeq:NM_000551.3 DiseaseEntity:clearcellrenalcellcarcinoma AgeOfPresentation:clearcellrenalcellcarcinoma:56 NoFamilyInfo SupplementalData cDNAposition:464 MutationType:splice_site_variant ClinVarID:223221 ClinVarID:Yes ProteinPosition:N/A AminoAcidChange:N/A CivicName:SpliceSite(c.464-1G>T) inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    www-nature-com.proxy1.lib.uwo.ca/articles/ng.2699
  103. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    A retrospective case study of sunitinib treatment in three patients with Von Hippel-Lindau disease
    1
    1. ClingenBaseline 26 Oct 2026
      VHL mutation c. 232A>T; p. Asn78Tyr in this patient. The same point mutation of VHL was identified in three family members including one sister

      PatientID: N/A (proband's sister)

      KindredID: 2

      Case: F, 40Y0M, Ethnicity Unknown

      DiseaseAssertion: assumed VHL

      FamilyInfo: The same point mutation of VHL (c. 232A>T; p.Asn78Tyr) was identified in three family members including one sister, one brother and one nephew. Her sister was found with adrenal pheochromocytoma, cerebellar hemangioblastoma, and her brother and nephew refused for further examinations for VHL-related lesions. Her mother died of stroke at early of 50 years.

      CasePresentingHPOs: HP:0030405 (pancreatic endocrine tumour)

      CaseHPOFreeText: patient died of the hemorrhagic stroke at age of 40 years.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.N78Y (c.232A>T)

      LegacyVariant: N/A

      ClinVar: 223167 https://www.ncbi.nlm.nih.gov/clinvar/variation/223167/

      CAID: CA357056 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.232A%3ET

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transversion

      CivicName: N78Y (c.232A>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:pancreaticendocrinetumor Mutation:Germline cDNAposition:232 ProteinPosition:78 AminoAcidChange:ASNtoTYR CAiD:CA357056 ClinVarID:223167 CivicName:N78Y(c.232A>T) Familial MutationType:missense_variant;transversion ClinVarID:Yes AssumedRefSeq:NM_000551.3 inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC6154838/
  104. journals.lww.com journals.lww.com
    Six weeks into the 2019 coronavirus disease (COVID-19)... : Chinese Medical Journal
    1
    1. ClingenBaseline 26 Oct 2026

      PatientID: None

      KindredID: 12

      Case: F, 20Y0M, Chinese

      DiseaseAssertion: asymptomatic

      FamilyInfo: Patient 12's 20 year old niece (this patient) was identified as a carrier of the same mutation as patient 12. Patient 12 was noted to not have a family history of VHL or other lesions associated with VHL disease.

      CasePresentingHPOs: N/A

      CaseHPOFreeText: The 20-year-old niece of patient 12 was identified as a carrier of the same mutation by genetic screening (no evidence of VHL disease.)

      CaseNotHPOs:None

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.P86L (c.257C>T)

      LegacyVariant: c.470C>T

      CaseProblemVariant Free Text: N/A

      ClinVar: 182977, https://www.ncbi.nlm.nih.gov/clinvar/variation/182977/

      CAID: CA020186

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_transition

      CivicName: P86L (c.257C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Chinese Mutation:Germline AssumedRefSeq:AF010238.1 cDNAposition:257 DiseaseEntity:asymptomatic ProteinPosition:86 AminoAcidChange:PROtoLEU ClinVarID:182977 CAiD:CA020186 MutationType:missense_variant;transition CivicName:P86L(c.257C>T) Familial ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    journals.lww.com/cmj/fulltext/2011/01020/molecular_basis_of_von_hippel_lindau_syndrome_in.16.aspx
  105. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Clinical and molecular characterization of Brazilian families with von Hippel-Lindau disease: a need for delineating genotype-phenotype correlation
    1
    1. ClingenBaseline 26 Oct 2026
      PMID: 20567917

      PatientID: 2

      KindredID: 2

      Case: F, 29Y0M, Brazilian

      DiseaseAssertion: VHL

      FamilyInfo: VHL type 1. Genetic testing has been performed in her parents and brother with negative results. Her only child has not undergone predictive testing yet.

      CasePresentingHPOs: HP:0030393; HP:0009711; HP:0010797; HP:0000107; HP:0001737; HP:0001407 (endolymphatic sac tumor; retinal capillary hemangioma; hemangioblastoma; renal cysts; pancreatic cysts; hepatic cysts)

      CaseHPOFreeText: endolymphatic sac tumor diagnosed at 11Y, retinal angiomas at 16Y; hemangioblastoma, renal, pancreatic, and hepatic cysts at 29Y

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: Yes

      Variant: p.Q73* (c.217C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 223164 https://www.ncbi.nlm.nih.gov/clinvar/variation/223164/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: Q73* (c.217C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Brazilian DiseaseEntity:VHL DiseaseEntity:endolymphaticsactumor DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:hepaticcysts DiseaseEntity:renalcyst DiseaseEntity:pancreaticcysts DiseaseEntity:hemangioblastoma AgeOfPresentation:endolymphaticsactumor:11 AgeOfPresentation:retinalcapillaryhemangioma:16 AgeOfPresentation:hemangioblastoma:29 AgeOfPresentation:hepaticcysts:29 AgeOfPresentation:pancreaticcysts:29 Mutation:Germline RefSeq:NM_000551.2 NonFamilial FamilyPedigree ClinVarID:223164 ClinVarID:Yes MutationType:stop_gained ProteinPosition:73 cDNAposition:217 CivicName:Q73*(c.217C>T) AminoAcidChange:GLNtoTER SupplementalData inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/20567917/
  106. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Clinical presentation of Von Hippel Lindau syndrome type 2B associated with VHL p.A149S mutation in a large Turkish family
    1
    1. ClingenBaseline 26 Oct 2026
      Nine patients were diagnosed with pheochromocytoma. Lumbal spinal hemangioblastoma and pancreatic neuroendocrine tumor without pheochromocytoma were detected in one patient. In patients with pheochromocytoma, additional tumors, such as retinal angioma, renal cell carcinoma, pancreatic serous cystadenoma, and pancreatic neuroendocrine tumors were detected. All patients were diagnosed as VHL syndrome type 2B.

      PatientID: III-10

      KindredID: 1

      Case: F, 27Y0M, Turkish

      DiseaseAssertion: VHL

      FamilyInfo: 17 family members from three generations were examined with the c.445G>T mutation and diagnosed with VHL type 2B. 11 individuals had clinical manifestations and 6 were asymptomatic carriers. One additional member (II-9) had passed before testing however were likely a carrier of the mutation. This patient’s mother, brother, and more, had the mutation. See Fig. 1 for full family pedigree.

      CasePresentingHPOs: HP:0006748; HP:0005584 (adrenal pheochromocytoma; renal cell carcinoma)

      CaseHPOFreeText: bilateral adrenal pheochromocytoma, right RCC

      CaseNotHPOs: HP:0030393; HP:0009715 (endolymphatic sac tumor, papillary cystadenoma of the epididymis) 

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.A149S (c.445G>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 127829 https://www.ncbi.nlm.nih.gov/clinvar/variation/127829/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: A149S (c.445G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Turkish Mutation:Germline AssumedRefSeq:NM_000551.3 DiseaseEntity:VHL DiseaseEntity:renalcellcarcinoma DiseaseEntity:adrenalpheochromocytoma ClinVarID:127829 ClinVarID:Yes CivicName:A149S(c.445G>T) cDNAposition:445 ProteinPosition:149 AminoAcidChange:ALAtoSER MutationType:missense_variant;transversion Familial FamilyPedigree inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/23673869/
  107. www.jmdjournal.org www.jmdjournal.org
    Optimization of Next-Generation Sequencing Technologies for von Hippel Lindau (VHL) Mosaic Mutation Detection and Development of Confirmation Methods
    1
    1. ClingenBaseline 26 Oct 2026
      M198434NoCentral nervous system Hb, two RCC3Yesc.490C>T p.(Gln164*)3.33.5Tissue not available

      PatientID: None

      KindredID: 4

      Case: M, 34Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: None.

      CasePresentingHPOs: HP:0010797, HP:0005584 (hemangioblastoma, renal cell carcinoma)

      CaseHPOFreeText: The patient had three tumours, one hemangioblastoma of the central nervous system and two renal cell carcinomas.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: Previously published in 24301059.

      SupplementalData: N/A

      Variant: p.Q164* (c.490C>T)

      LegacyVariant: N/A

      ClinVarID: 223228 https://www.ncbi.nlm.nih.gov/clinvar/variation/223228/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: The patient had a mosaic mutation with a mutated allele frequency of 3.3%. Copy number events of the mutated and wild type allele are available in table S4 of the supplemental.

      MutationType: stop_gained

      CivicName: Q164* (c.490C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL Mutation:Germline NonFamilial DiseaseEntity:renalcellcarcinoma DiseaseEntity:hemangioblastoma RefSeq:NM_000551.3 SupplementalData ProteinPosition:164 CivicName:Q164*(c.490C>T) cdnaposition:490 MutationType:stop_gained ClinVarID:223228 ClinVarID:Yes AminoAcidChange:GLNtoTER inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    jmdjournal.org/article/S1525-1578(18)30259-9/fulltext
  108. www.sciencedirect.com www.sciencedirect.com
    Identification of a new VHL exon and complex splicing alterations in familial erythrocytosis or von Hippel-Lindau disease
    1
    1. ClingenBaseline 26 Oct 2026
      F10

      PatientID: I.1

      KindredID: F10

      Case: M, Age Unknown, Ethnicity Unknown

      DiseaseAssertion: Asymptomatic

      FamilyInfo: This patient’s partner and two children were all carriers of the D143= (c.429C>T) germline VHL variant. Their son was diagnosed with splenomegaly and polycythemia and was homozygous for the variant. All other family members were asymptomatic.

      CasePresentingHPOs: N/A

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.D143= (c.429C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 416990, https://www.ncbi.nlm.nih.gov/clinvar/variation/416990/

      CAID: N/A

      gnomAD: 0.000007953, https://gnomad.broadinstitute.org/variant/3-10188286-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_variant;transition; synonymous_variant

      CivicName: D143= (c.429C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalRecessive DiseaseEntity:asymptomatic Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:429 ProteinPosition:143 AminoAcidChange:ASPtoASP ClinVarID:416990 ClinVarID:Yes MultipleGeneVariants MutationType:missense_variant;transition MutationType:synonymous_variant CivicName:D143=(c.429C>T) FamilyPedigree inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    sciencedirect.com/science/article/pii/S0006497120320206
  109. ascopubs.org ascopubs.org
    Genetic Testing in Pheochromocytoma or Functional Paraganglioma | Journal of Clinical Oncology
    1
    1. ClingenBaseline 26 Oct 2026
      Arg167Trp

      GroupID: 9

      DiseaseAssertion: Neuroendocrine neoplasm (pheochromocytoma or paraganglioma)

      GroupSize: 3

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: Ethnicity unknown

      GroupAgeRange: N/A

      GroupInfo: This mutation (p.R167W (c.499C>T)) was found in 3 patients, 2 with a family history and/or a syndromic presentation, and 1 patient with an apparently sporadic presentation.

      GroupPresentingHPOs: HP:0100634 (Neuroendocrine neoplasm)

      GroupHPOFreeText: Patients with a pheochromocytoma or a functional paraganglioma were recruited from several different French clinical centers participating in several clinical research networks (Cortico et Medullosurrènale: les Tumeurs Endocrines, Paragan-Glioma Network, Groupe des Tumeurs Endocrines)

      GroupNotHPOs: N/A

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: RET, NF1, SDHB/SDHC/SDHD

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 2218 https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954 https://gnomad.broadinstitute.org/variant/3-10191506-C-T

      VariantEvidence: N/A

      MutationType: missense_variant; transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:neuroendocrineneoplasm Mutation:Germline RefSeq:NM_000551.2 CivicName:R167W(c.499C>T) cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP MutationType:missense_variant;transition Familial ClinVarID:2218 ClinVarID:Yes PreviousTesting:RET PreviousTesting:SDHB PreviousTesting:SDHC PreviousTesting:SDHD PreviousTesting:NF1 inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    ascopubs.org/doi/10.1200/JCO.2005.03.1484
  110. iovs.arvojournals.org iovs.arvojournals.org
    Retinal Hemangioblastoma in von Hippel-Lindau Disease: A Clinical and Molecular Study
    2
    1. ClingenBaseline 26 Oct 2026
      499C→T Ts Exon 3 167 CGG R R167W

      GroupID: 47

      DiseaseAssertion: VHL

      GroupSize: 15

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: French

      GroupAgeRange: N/A

      GroupInfo: 15 patients are listed with this mutationt; any relation is unknown.

      GroupPresentingHPOs: HP:0009711 (retinal capillary hemangioma)

      GroupHPOFreeText: 5 patients were said to have retinal HBs. Other manifestations are not clearly stated.

      GroupNotHPOs: N/A

      GroupNotHPOFreeText: the other 10 members are said to not have retinal HBs

      GroupPreviousTesting: N/A

      PreviouslyPublished: some are possibly published in PMID:15300849

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      CaseProblemVariantFreeText: N.A

      LegacyVariant: N/A

      ClinVarID: 2218 https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954 https://gnomad.broadinstitute.org/variant/3-10191506-C-T

      VariantEvidence: N/A

      MutationType: missense_variant; transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:499 CivicName:R167W(c.499C>T) ProteinPosition:167 AminoAcidChange:ARGtoTRP MutationType:missense_variant;transition Ethnicity:French NoFamilyInfo ClinVarID:2218 ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    2. ClingenBaseline 24 Oct 2026
      136G→T Ts Exon 1 46 GAG E E46X

      GroupID: 1

      Case: Age unknown, Sex unknown, French

      DiseaseAssertion: VHL

      FamilyInfo: None - one member documented here

      CasePresentingHPOs: HP:0009711 (retinal capillary hemangioma)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: Possibly published in PMID:15300849

      SupplementalData: N/A

      Variant: p.E46* (c.136G>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: N/A

      CAID: CA351748085 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.136G%3ET

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: E46* (c.136G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant NoFamilyInfo DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:136 ProteinPosition:46 MutationType:stop_gained CivicName:E46*(c.136G>T) AminoAcidChange:GLUtoTER CAID:CA351748085 ClinVarID:N/A Ethnicity:French inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    iovs.arvojournals.org/article.aspx
  111. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Management of Gene Variants of Unknown Significance: Analysis Method and Risk Assessment of the VHL Mutation p.P81S (c.241C>T)
    2
    1. ClingenBaseline 25 Oct 2026
      his two brothers (32 and 36 years),

      PatientID: None

      KindredID: 1

      Case: M, 36Y0M, Danish

      DiseaseAssertion: Asymptomatic

      FamilyInfo: The patient's half brothers both carried the mutation, one was asymptomatic and one had renal cell carcinoma. The patient's mother was found to carry the mutation and had breast cancer. The maternal grandmother also harboured the mutation but was asymptomatic. See Figure 1 for family pedigree.

      CasePresentingHPOs: N/A

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.P81S (c.241C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2233 https://www.ncbi.nlm.nih.gov/clinvar/variation/2233/

      CAID: N/A

      gnomAD: 0.0002179 https://gnomad.broadinstitute.org/variant/3-10183772-C-T

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName:P81S (c.241C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline AssumedRefSeq:NM_000551.3 DiseaseEntity:asymptomatic Familial FamilyPedigree Ethnicity:Danish ProteinPosition:81 CivicName:P81S(c.241C>T) cDNAposition:241 AminoAcidChange:PROtoSER ClinVarID:2233 ClinVarID:Yes MutationType:missense_variant;transition ExperimentalAssay inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    2. ClingenBaseline 25 Oct 2026
      proband’s mother (52 years)

      PatientID: None

      KindredID: 1

      Case: F, 52Y0M, Danish

      DiseaseAssertion: Breast carcinoma

      FamilyInfo: The patient had three sons all of whom carried the VHL mutation. Two of the sons were asymptomatic and one had renal cell carcinoma. The affected son also had a P2P mutation and he had a child who was found to have the VHL mutation (P2P). The patient's mother had the mutation but was also asymptomatic. See Figure 1 for family pedigree.

      CasePresentingHPOs: HP:0003002 (Breast carcinoma)

      CaseHPOFreeText: The patient had breast cancer at age 34.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.P81S (c.241C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2233 https://www.ncbi.nlm.nih.gov/clinvar/variation/2233/

      CAID: N/A

      gnomAD: 0.0002179 https://gnomad.broadinstitute.org/variant/3-10183772-C-T

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName:P81S (c.241C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline DiseaseEntity:Breastcarcinoma Familial FamilyPedigree Ethnicity:Danish AgeOfPresentation:Breastcarcinoma:34 ProteinPosition:81 CivicName:P81S(c.241C>T) cDNAposition:241 AminoAcidChange:PROtoSER AssumedRefSeq:NM_000551.3 MutationType:missense_variant;transition ClinVarID:2233 ClinVarID:Yes ExperimentalAssay inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC5321774/
  112. www.sciencedirect.com www.sciencedirect.com
    Extraneuraxial hemangioblastoma: A clinicopathologic study of 10 cases with molecular analysis of the VHL gene
    1
    1. ClingenBaseline 25 Oct 2026
      Case 3 (intradural tumor of T7 spinal nerve roots), which was first thought to be sporadic (non-familial) in 2001, was then re-classified as “HB-only VHLD” (form fruste of VHLD) after the patient’s sister, aged 53, was diagnosed with cerebellar HB (in the sister a germline point mutation and 2 somatic point mutations were found in the DNA of the cerebellar HB, and the case was included as case HB-25 in another study [28]). To the best of our knowledge, this is the first case of a patient with “HB-only VHLD” having clinical expression outside CNS.

      PatientID: N/A

      KindredID: 3

      Case: F, 53Y0M, Italian

      DiseaseAssertion: VHL

      FamilyInfo: Sister was thought to be sporadic (non familial) in 2001 with a spinal T7 tumor - genetic testing in this paper describes her (the sister, case 3) without any mutations.

      CasePresentingHPOs: HP:0006880 (cerebellar hemangioblastoma)

      CaseHPOFreeText: The patient had a single cerebellar hemangioblastoma that was diagnosed at age 53. She had a germline point and 2 somatic point mutations found in the DNA of her CHB. These mutations are discussed further in PMID: 24335534

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: 24335534 (pt. HGB-25)

      SupplementalData: Supplemental Digital Content 1. Primer Sequences for VHL gene amplification, LOH and methylation analysis.

      Variant: p.D126Rfs*6 (c.375_376insA)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: N/A

      CAID: CA2573320316 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2573320316

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: plus_1_frameshift_variant

      CivicName: P25L(c.74C>T) and D126Rfs*6(c.375_376insA) and E55Rfs(c.163delG)

      MultipleGeneVariants: Somatic, VHL, c.163delG (p.Glu55Argfs), Germline, VHL, c.74C>T (p.Pro25Leu)

      InheritancePattern:AutosomalDominant Mutation:Somatic Familial Ethnicity:Italian DiseaseEntity:VHL AgeOfPresentation:cerebellarhemangioblastoma:53 DiseaseEntity:cerebellarhemangioblastoma MultipleVHLVariants CAID:CA2573320316 ClinVarID:N/A MutationType:plus_1_frameshift_variant CivicName:P25L(c.74C>T)andD126Rfs*6(c.375_376insA)andE55Rfs(c.163delG) AminoAcidChange:ASPtoARG cDNAposition:375 ProteinPosition:126 AssumedRefSeq:NM_000551.3 inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    sciencedirect.com/science/article/pii/S0344033818303327
  113. onlinelibrary-wiley-com.uhn.idm.oclc.org onlinelibrary-wiley-com.uhn.idm.oclc.org
    Germline mutations and genotype–phenotype correlations in patients with apparently sporadic pheochromocytoma/paraganglioma in Korea
    1
    1. ClingenBaseline 25 Oct 2026
      Case 3 VHL 16 Female PHEO 2.5 None None Recurred NE/NM Exon 1 c.242C>T p.Pro81Leu Missense

      PatientID: 3

      KindredID: 3

      Case: F, 16Y0M, Korean

      DiseaseAssertion: pheochromocytoma

      FamilyInfo: No family history of PPGLs

      CasePresentingHPOs: HP:0002666 (pheochromocytoma)

      CaseHPOFreeText: recurrent PPGL - initially removed at 2.5cm; no metastases; increased NE/NM hormone levels

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.P81L (c.242C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 36899 https://www.ncbi.nlm.nih.gov/clinvar/variation/36899/

      CAID: N/A

      gnomAD: 0.000004349 https://gnomad.broadinstitute.org/variant/3-10183773-C-T

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: P81L (c.242C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Korean DiseaseEntity:pheochromocytoma Mutation:Germline AssumedRefSeq:NM_000551.3 ProteinPosition:81 CivicName:P81L(c.242C>T) cDNAposition:242 MutationType:missense_variant;transition AminoAcidChange:PROtoLEU ClinVarID:36899 ClinVarID:Yes NonFamilial inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    onlinelibrary-wiley-com.uhn.idm.oclc.org/doi/full/10.1111/cge.12304
  114. onlinelibrary-wiley-com.uhn.idm.oclc.org onlinelibrary-wiley-com.uhn.idm.oclc.org
    Frequency of Von Hippel-Lindau germline mutations in classic and non-classic Von Hippel-Lindau disease identified by DNA sequencing, Southern blot analysis and multiplex ligation-dependent probe amplification
    2
    1. ClingenBaseline 25 Oct 2026
      23 c.583C>T p.Gln195X p.Q195X Familial VHL

      GroupID/ KindredID: 23

      DiseaseAssertion: VHL

      GroupSize: 2

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: N/A

      GroupAgeRange: N/A

      GroupInfo: Described are 2 patients with this familial VHL mutation. They belong to family 23 and have the germline VHL mutation of c.583C>T

      GroupPresentingHPOs: HP:0009711; HP:0010797; HP:0002666 (retinal capillary hemangioma, hemangioblastoma, pheochromocytoma)

      GroupHPOFreeText: 2 familial patients affected; 2 rHAB (retinal hemangioblastoma), 1 cHAB (central nervous system hemangioblastoma), 1 pheochromocytoma.

      GroupNotHPOs: HP:0005584; HP:0001737 (renal cell carcinoma, pancreatic cysts)

      GroupNotHPOFreeText: None have the above manifestations

      GroupPreviousTesting: N/A

      PreviouslyPublished: Previously reported, HGMD (Human Gene Mutation Database: http://uwcmml1s.uwcm.ac.uk/uwcm/mg/search/120488.html)

      SupplementalData: N/A

      Variant: p.Q195* (c.583C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVar: 428794 https://www.ncbi.nlm.nih.gov/clinvar/variation/428794/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: Q195* (c.583C>T)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:hemangioblastoma DiseaseEntity:pheochromocytoma Mutation:Germline RefSeq:NM_000551.2 cDNAposition:583 ProteinPosition:195 AminoAcidChange:GLNtoTER CivicName:Q195*(c.583C>T) MutationType:stop_gained CAID:CA70052558 ClinVarID:428794 Familial ClinVarID:Yes InheritancePattern:AutosomalDominant ExperimentalAssay inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
    2. ClingenBaseline 23 Oct 2026
      20 c.481C>T p.Arg161X p.R161X Familial VHL

      GroupID/ KindredID: 20

      Case: Age, Sex, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: Familial VHL; One registrant belonging to family 20 has the germline VHL mutation of c.481C>T.

      CasePresentingHPOs: HP:0009711; HP:0000107; HP:0001737 (retinal capillary hemangioma, renal cyst, pancreatic cysts)

      CaseHPOFreeText: N/A

      CaseNotHPOs: HP:0010797; HP:0002666; HP:0005584 (hemangioblastoma, pheochromocytoma, renal cell carcinoma)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: Previously reported, HGMD (Human Gene Mutation Database: http://uwcmml1s.uwcm.ac.uk/uwcm/mg/search/120488.html)

      SupplementalData: N/A

      Variant: p.R161* (c.481C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 2217 https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: R161* (c.481C>T)

      MultipleGeneVariants: N/A

      RefSeq:NM_000551.2 Mutation:Germline MutationType:stop_gained Familial ProteinPosition:161 cDNAposition:481 CivicName:R161*(c.481C>T) AminoAcidChange:ARGtoTER CAID:CA020408 ClinVarID:2217 DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:renalcyst DiseaseEntity:pancreaticcysts ClinVarID:Yes InheritancePattern:AutosomalDominant ExperimentalAssay inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    onlinelibrary-wiley-com.uhn.idm.oclc.org/doi/full/10.1111/j.1399-0004.2007.00827.x
  115. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Improved Detection of Germline Mutations in Korean VHL Patients by Multiple Ligation-dependent Probe Amplification Analysis
    1
    1. ClingenBaseline 25 Oct 2026
      586A>T

      PatientID: 3

      KindredID: 3

      Case: F, 22Y0M, Korean

      DiseaseAssertion: VHL

      FamilyInfo: Family history present.

      CasePresentingHPOs: HP:0010797 (hemangioblastoma)

      CaseHPOFreeText: Multiple involvements of central nervous system HB.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.K196* (c.586A>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVar: 196284 https://www.ncbi.nlm.nih.gov/clinvar/variation/196284/

      CAID: CA020507 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.586A%3ET

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: K196* (c.586A>T)

      MultipleGeneVariants: N/A

      Ethnicity:Korean DiseaseEntity:VHL DiseaseEntity:hemangioblastoma Mutation:Germline RefSeq:NM_000551.2 cDNAposition:586 ProteinPosition:196 ClinVarID:196284 CAID:CA020507 MutationType:stop_gained Familial AminoAcidChange:LYStoTER CivicName:K196*(c.586A>T) InheritancePattern:AutosomalDominant ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC2650969/
  116. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Late recurrence after surgical resection of a pancreatic tumor in von Hippel-Lindau disease
    1
    1. ClingenBaseline 25 Oct 2026
      The long clinical history of a 45-year-old woman started at 22 years of age when she had surgery for a right adrenal pheochromocytoma. Two years later, a pancreaticoduodenectomy was performed to remove a pancreatic mass which turned out to be a pancreatic neuroendocrine tumor. After a long period of relative wellness, 21 years after the surgical resection of her primary pancreatic neuroendocrine tumor, abdominal lymph node metastases of pancreatic neuroendocrine origin occurred. In fact, three abdominal nodules were removed by laparoscopic surgery, and the histological examination showed well-differentiated neuroendocrine tumors with similar immunohistochemical characteristics and Ki67 below 1%.

      PatientID: N/A (case)

      KindredID: 1

      Case: F, 45Y0M, Italian

      DiseaseAssertion: Assumed VHL

      FamilyInfo: Genetic analysis was performed on the patients relatives, including her daughter. Her 55Y0M brother had the same mutation but no clinical signs of VHL disease.

      CasePresentingHPOs: HP:0006748; HP:0030405 (adrenal pheochromocytoma, pancreatic neuroendocrine tumour)

      CaseHPOFreeText: At 22Y0M, she had surgery for a right adrenal pheochromocytoma. Two years later, a pancreatic oduodenectomy was performed to remove a pancreatic neuroendocrine tumor. 21 years later, abdominal lymph node metastases of the pancreatic neuroendocrine that was removed 21 years prior had occurred. Three abdominal nodules that were found to be neuroendocrine tumours immunohistochemical characteristics were removed. The patient’s clinical history suggested a hereditary endocrine syndrome.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.T157I (c.470C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 223223, https://www.ncbi.nlm.nih.gov/clinvar/variation/223223/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense variant; transition

      CivicName: T157I (c.470C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline MutationType:missense_variant;transition AssumedRefSeq:NM_000551.3 DiseaseEntity:adrenalpheochromocytoma DiseaseEntity:pancreaticendocrinetumor AgeOfPresentation:adrenalpheochromocytoma:22 AgeOfPresentation:pancreaticendocrinetumor:24 CivicName:T157I(c.470C>T) cDNAPosition:470 ProteinPosition:157 AminoAcidChange:THRtoILE ClinVarID:223223 ClinVarID:Yes Familial Ethnicity:Italian inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/19734639/
  117. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Contribution of endosonography in an uncommon case of pancreatic cysts
    1
    1. ClingenBaseline 25 Oct 2026
      This case concerns a 35-year-old woman referred to our Gastroenterology Department with long-standing dyspepsia and pancreatic cysts detected by ultrasound examination. There were no other symptoms, such as abdominal pain, weight loss, visual or hearing changes, headache or urinary complaints. The past medical and family histories were not of significance. There were no abnormal findings on examination.The patient underwent an abdominal computed tomography (CT) scan (Figure ​(Figure1),1), which showed an enlargement of the pancreas, especially in the cephalic region, with heterogeneous density due to the presence of multiple hypodense nodules dispersed throughout the parenchyma. The majority of these lesions were small, but one larger contrast-enhancing lesion of 22 mm was present in the uncinate process.Open in a separate windowFigure 1Computed tomography abdominal scan. A: Small cystic lesions dispersed throughout the pancreas; B: The largest lesion.Given the findings of the CT scan, we performed an abdominal magnetic resonance imaging (MRI) (Figure ​(Figure2),2), which revealed several cysts that had a high signal intensity on T2 weighted images.Open in a separate windowFigure 2Magnetic resonance imaging. Cyst lesions are bright on T2-weighted images.The patient underwent endosonography that confirmed the presence of multiple simple cysts throughout the entirety of the pancreas. The majority of the cysts were less than 1 cm in diameter, but two cysts were larger than 1 cm. One of the larger cysts was 16 mm in diameter and was located at the isthmus-body transition. This cyst and did not communicate with the main pancreatic duct and was aspirated. The content had a serous appearance, and cytological analysis revealed amorphous material, few erythrocytes and inflammatory cells (Figure ​(Figure33).Open in a separate windowFigure 3Endosonography. A, B show a large cyst of 16 mm in diameter without communication or dilatation of the pancreatic duct; C: Demonstrates aspiration of the cyst; D: Demonstrates its appearance after total aspiration.The largest cyst was 23 mm in diameter and was located in the head of the pancreas. The cyst had a honeycomb appearance characteristic of serous cystadenomas (Figure ​(Figure4A).4A). The cytology did not show evidence of cellular atypia (Figure ​(Figure4B).4B). The carninoembryonic antigen was < 0.6 ng/dL, and the amylase in the cystic content was 135 U/L.Open in a separate windowFigure 4The largest cyst was 23 mm in diameter and was located in the head of the pancreas. A: Endosonography. Cyst with a honeycomb appearance; B: Cytology (papanicolaou stain, × 100). Benign pancreatic cysts.The endosonography also showed cysts in the left kidney and in the spleen (Figure ​(Figure5).5). The findings described were compatible with simple cysts and pancreatic serous cystadenomas and provided an indication for genetic testing for VHL. The sequencing of the VHL gene revealed one pathogenic heterozygous mutation in exon 1 (c.269A > T), confirming the diagnosis of VHL disease.Open in a separate windowFigure 5Endosonography. A: A cyst in the renal cortex; B: A cyst in the spleen.The patient underwent a MRI of the brain and entire spine and no hemangioblastomas were detected. The abdominal MRI scan excluded renal carcinoma. The plasma and urinary catecholamines and the urinary vanilmandelic acid were normal, excluding pheocromocytoma. The patient was also referred for examination of the retina and ear, nose and throat, including audiometry. There were no abnormal findings, which excluded angiomas of the retina and endolymphatic sac tumors, respectively.

      PatientID: None

      KindredID: 1

      Case: F, 35Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: Her family was genetically tested, and the same mutation was found in her 7 year-old daughter. Assumed de novo.

      CasePresentingHPOs: HP:0410281; HP:0001737; HP:0005562; HP:0030423 (Dyspepsia, Pancreatic cysts, Multiple renal cysts, Splenic cyst)

      CaseHPOFreeText: Admitted with long-standing dyspepsia and pancreatic cysts detected by ultrasound examination. There were no other symptoms, such as abdominal pain, weight loss, visual or hearing changes, headache or urinary complaints. The past medical and family histories were not of significance. There were no abnormal findings on examination.CT scan showed an enlargement of the pancreas, especially in the cephalic region, with heterogeneous density due to the presence of multiple hypodense nodules dispersed throughout the parenchyma. Abdominal MRI revealed several cysts. Endosonography that confirmed the presence of multiple simple cysts throughout the entirety of the pancreas as well as cysts in the left kidney and in the spleen. The findings described were compatible with simple cysts and pancreatic serous cystadenomas.

      CaseNotHPOs: HP:0006880; HP:0009711; HP:0009713; HP:0005584; HP:0002666; HP:0030393 (Cerebellar hemangioblastoma, Retinal capillary hemangioma, Spinal hemangioblastoma, Renal cell carcinoma, Pheochromocytoma, Endolymphatic sac tumor)

      CaseNotHPOFreeText: MRI of the brain and entire spine and no hemangioblastomas were detected. Abdominal MRI scan excluded renal carcinoma.The plasma and urinary catecholamines and the urinary vanilmandelic acid were normal, excluding pheochromocytoma. Examination of the retina and ear, nose and throat, including audiometry excluded angiomas of the retina and endolymphatic sac tumors, respectively.

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.N90I (c.269A>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 223172, https://www.ncbi.nlm.nih.gov/clinvar/variation/223172/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: N90I (c.269A>T)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:dyspepsia DiseaseEntity:pancreaticcysts DiseaseEntity:renalcyst DiseaseEntity:spleniccyst AgeOfPresentation:dyspepsia:35 AgeOfPresentation:pancreaticcysts:35 AgeOfPresentation:renalcyst:35 AgeOfPresentation:spleniccyst:35 Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:269 ProteinPosition:90 AminoAcidChange:ASNtoILE ClinVarID:223172 ClinVarID:Yes MutationType:missense_variant;transversion CivicName:N90I(c.269A>T) NonFamilial InheritancePattern:DeNovoAssertion inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC3797906/
  118. erc.bioscientifica.com erc.bioscientifica.com
    Head and neck paragangliomas: genetic spectrum and clinical variability in 79 consecutive patients
    1
    1. ClingenBaseline 25 Oct 2026
      VHL1c.242C>Tp.Pro81Leu1RCB c

      PatientID: N/A

      KindredID: 2

      Case: Sex Unknown, Age Unknown, Ethnicity Unknown

      DiseaseAssertion: paraganglioma

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0002668 (paraganglioma)

      CaseHPOFreeText: Paraganglioma of the head and neck region (HNPGL): Right carotid body; nonsecreting paraganglioma

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: MAX, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.P81L (c.242C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 36899 https://www.ncbi.nlm.nih.gov/clinvar/variation/36899

      CAID: N/A

      gnomAD: 0.000004349 https://gnomad.broadinstitute.org/variant/3-10183773-C-T

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: P81L (c.242C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline DiseaseEntity:paraganglioma CivicName:P81L(c.242C>T) cDNAposition:242 ProteinPosition:81 AminoAcidChange:PROtoLEU MutationType:missense_variant;transition ClinVarID:36899 ClinVarID:Yes NoFamilyInfo AssumedRefSeq:NM_000551.3 PreviousTesting:MAX/SDHA/SDHB/SDHC/SDHD/SDHAF2/TMEM127 inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    erc.bioscientifica.com/view/journals/erc/19/2/149.xml
  119. www.ajkd.org www.ajkd.org
    Arterial Hypertension in a 10-Year-Old Girl
    1
    1. ClingenBaseline 25 Oct 2026
      A previously healthy 10-year-old girl presented with occasional routine blood pressure measurements by her pediatrician above the 99th percentile for her age, sex, and height. She had noted mild hand edema over the previous days and reported recent nocturia. She was taking no medications. Family history was unremarkable. The physical examination was without significant findings other than an elevated blood pressure of 139/113 mm Hg. Urine tests showed boderline moderate albuminuria (albumin-creatinine ratio of 50 mg/g). There was no hematuria.On ultrasound, kidney size and parenchyma were unremarkable but an increased flow rate of the left renal artery in color duplex sonography was detected (systolic flow rate: right, 100 cm/s; left, 300 cm/s [age-adjusted normal values range from 72 to 104 cm/s]) (Fig 1A and B). No additional finding was reported. Magnetic resonance (MR) angiography of the kidney vessels was performed (Fig 2A) and antihypertensive therapy was initiated.

      PatientID: N/A

      KindredID: 1

      Case: F, 10Y0M, Ethnicity Unknown

      DiseaseAssertion: Assumed VHL

      FamilyInfo: No family history, authors indicate that the variant occurred de novo.

      CasePresentingHPOs: HP:0007514; HP:0000017; HP:0004421; HP:0012594; HP:0002666; HP:0001920 (Edema of the dorsum of hands; Nocturia; Elevated systolic blood pressure; Moderate albuminuria; Pheochromocytoma; Renal artery stenosis)

      CaseHPOFreeText: Patient presented with occasional high routine blood pressure at 10Y0M. She noted mild hand edema over the past days and reported recent nocturia. Physical examination appeared normal other than elevated blood pressure of 139/113 mm Hg. Urine tests showed moderate albuminuria (albumin-creatinine ratio of 50 mg/g), as well as high levels of noradrenaline and normetanephrine, suggestive of benign pheochromocytoma. Ultrasound showed normal kidney size and parenchyma, but color duplex sonography revealed increased flow rate of the left renal artery. This finding suggests renal artery stenosis. Magnetic Resonance Angiography of the kidney vessels showed a solid tumor that had cystic features. Tumor resection normalized blood pressure and pathologic examination of the removed tumor confirmed pheochromocytoma. Patient was diagnosed with secondary hypertension due to compression of renal vessels and catecholamine production by vHL-associated pheochromocytoma. Antihypertensive therapy with phenoxybenzamine as α blockade was initiated, along with subsequent expansion of the therapy with a β-blocker. Authors mention that the patient is in complete remission with no other manifestations of VHL disease and is receiving close follow-up.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.G104V (c.311G>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 223183, https://www.ncbi.nlm.nih.gov/clinvar/variation//223183/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transversion

      CivicName: G104V (c.311G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline MutationType:missense_variant;transversion AssumedRefSeq:NM_000551.3 NonFamilial DiseaseEntity:VHL DiseaseEntity:pheochromocytoma AgeOfPresentation:pheochromocytoma:10 DiseaseEntity:renalarterystenosis AgeOfPresentation:renalarterystenosis:10 ClinVarID:Yes ClinVarID:223183 CivicName:G104V(c.311G>T) cDNAPosition:311 ProteinPosition:104 AminoAcidChange:GLYtoVAL InheritancePattern:DeNovoAssertion inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    ajkd.org/article/S0272-6386(20)31156-2/fulltext
  120. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    VHL mosaicism can be detected by clinical next-generation sequencing and is not restricted to patients with a mild phenotype
    1
    1. ClingenBaseline 25 Oct 2026
      simultaneously analysed with his daughter's DNA who had a heterozygous p.(R161*) VHL mutation.

      PatientID: None

      KindredID: 8

      Case: F, Age Unknown, Ethnicity Unknown

      DiseaseAssertion: Asymptomatic

      FamilyInfo: Her father harboured the same VHL mutation and presented with bilateral renal cell carcinoma.

      CasePresentingHPOs: N/A

      CaseHPOFreeText: The patient had bilateral renal cell carcinoma at age 48.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R161* (c.481C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 2217 https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: She had a heterozygous p.R161* mutation.

      MutationType: stop_gained

      CivicName: R161* (c.481C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:asymptomatic Mutation:Germline MutationType:stop_gained Familial ProteinPosition:161 CivicName:R161*(c.481C>T) cDNAposition:481 RefSeq:NM_000551.3 ClinVarID:Yes ClinVarID:2217 AminoAcidChange:ARGtoTER inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC4135403/
  121. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    A long-term survivor of metachronous liver metastases of pancreatic serous cystic neoplasm associated with von Hippel-Lindau disease
    1
    1. ClingenBaseline 25 Oct 2026
      Case presentationA 35-year-old woman with VHL underwent total pancreatectomy and right nephrectomy for pancreatic SCN and renal cell carcinoma, respectively. At the 4th year follow-up examination after the resection, contrast-enhanced computed tomography (CT) and gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) showed arterially hyper-enhanced neoplastic lesions in the segment VI and VIII of the liver. Partial resections of the liver were performed 53 months after the initial surgery. At the 6th month follow-up examination from the second surgery, one and two tumors located in the liver segment III, and VIII, respectively, were detected by contrast-enhanced CT and Gd-EOB-DTPA-enhanced MRI. Anterior segmentectomy and partial resection of the segment III were performed 66 months after the initial surgery and 13 months after the second, respectively. The tumors were pathologically diagnosed as liver metastases of pancreatic SCN synonymous with serous cystadenocarcinoma. She remains disease-free without recurrence 6.5 years after the last operation.

      PatientID: 1

      KindredID: 1

      Case: F, 47Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: No family history.

      CasePresentingHPOs: HP:0006880; HP:0002894; HP:0005584 (Cerebellar Hemangioblastoma; neoplasm of the pancreas; renal cell carcinoma)

      CaseHPOFreeText: At 35-year old, the female patient was diagnosed with VHL due to clinical presentation of pancreatic serous cystic neoplasm and renal cell carcinoma, and cerebellar hemangioblastomas that were surgically removed at age 21. The patient had underwent total pancreatectomy and right nephrectomy for pancreatic serous cystic neoplasm (SCN) and renal cell carcinoma (RCC), respectively. 4 years later, tumors in the liver were detected by CT scan and radiographically diagnosed as metasta-ses of the pancreatic SCN or RCC. Again, morphology and immunohistochemical findings of the resected tumors again were similar to the primary pancreatic SCN, thus diagnosed as multiple metachronous liver metastases of pancreatic SCN. As of 47Y, the patient has remained disease-free without any recurrence after the third operation.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: 21673464

      SupplementalData: N/A

      Variant: p.N78I (c.233A>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 223169 https://www.ncbi.nlm.nih.gov/clinvar/variation/223169/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: N78I (c.233A>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline AssumedRefSeq:NM_000551.3 DiseaseEntity:cerebellarhemangioblastoma DiseaseEntity:renalcellcarcinoma DiseaseEntity:neoplasmofthepancreas AgeOfPresentation:neoplasmofthepancreas:35 AgeOfPresentation:cerebellarhemangioblastoma:21 AgeOfPresentation:renalcellcarcinoma:25 ClinVarID:223169 ClinVarID:Yes CivicName:N78I(c.233A>T) cDNAposition:233 ProteinPosition:78 AminoAcidChange:ASNtoILE MutationType:missense_variant;transition NonFamilial inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC8245617/
  122. academic-oup-com.proxy1.lib.uwo.ca academic-oup-com.proxy1.lib.uwo.ca
    VHL2C Phenotype in a German von Hippel-Lindau Family with Concurrent VHL Germline Mutations P81S and L188V
    2
    1. ClingenBaseline 25 Oct 2026

      PatientID: 5

      KindredID: 1

      Case: F, Age Unknown, German

      DiseaseAssertion: VHL

      FamilyInfo: The patient's father (patient 1) was unaffected and did not carry the mutation. The patient's mother (patient 2) presented with pheochromocytoma and carried the mutation. The patient had three siblings; one died and was affected, another (patient 7) had both mutations and presented with pheochromocytoma, and the third (patient 6) was unaffected and carried neither mutation. Patient 7 had a child (patient 9) who also carried both mutations and presented with pheochromocytoma. The patient's uncle (patient 3) carried the mutation and was affected. He had a child with patient (4) who was unaffected. Their child (patient 8) carried both mutations and presented with pheochromocytoma. Patient 8 had two children; one that did not carry the mutation and was unaffected (patient 10) and another that carried both mutations but was disease free (patient 11). See Figure 3 for family pedigree.

      CasePresentingHPOs: HP:0002666 (pheochromocytoma)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: 8772572, 7563486

      SupplementalData: N/A

      Variant: p.P81S (c.241C>T)

      LegacyVariant: P81S (c.454C>T)

      CaseProblemVariantFreeText: N/A

      ClinVar: 2233 https://www.ncbi.nlm.nih.gov/clinvar/variation/2233/

      CAID: CA020148 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.241C%3ET

      gnomAD: 0.0002179 https://gnomad.broadinstitute.org/variant/3-10183772-C-T

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: P81S (c.241C>T) and L188V (c.562C>G)

      MultipleGeneVariants: Germline, VHL, c.562C>G (p.Leu188Val)

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:pheochromocytoma Ethnicity:German Mutation:Germline AssumedRefSeq:AF010238.1 ProteinPosition:81 AminoAcidChange:PROtoSER cDNAposition:241 CAID:CA020148 ClinVarID:2233 MultipleVHLVariants FamilyPedigree MutationType:missense_variant;transition ClinVarID:Yes Familial CivicName:P81S(c.241C>T)andL188V(c.562C>G) inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
    2. ClingenBaseline 24 Oct 2026

      PatientID: 11

      KindredID: 1

      Case: M, Age Unknown, German

      DiseaseAssertion: Asymptomatic

      FamilyInfo: The patient's father (patient 8) was had both mutations and presented with pheochromocytoma. The patient's brother (patient 10) did not carry the mutation and was unaffected. The patient's maternal grandfather (patient 3) presented with pheochromocytoma and carried both mutations. The patient's materal grandmother (patient 4) was unaffected and did not carry either mutation. The patient's great aunt (patient 2) presented with pheochromocytoma and had both mutations. Her husband (patient 1) was unaffected and did not carry either mutation. They had four children; one died and presented with pheochromocytoma, two (patient 5 and 7) had both mutations and presented with pheochromocytoma, and one child (patient 6) was unaffected and carried neither mutation. Patient 7 had a child (patient 9) who also carried both mutations and presented with pheochromocytoma. See Figure 3 for family pedigree.

      CasePresentingHPOs: N/A

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.P81S (c.241C>T)

      LegacyVariant: P81S (c.454C>T)

      CaseProblemVariantFreeText: N/A

      ClinVar: 2233 https://www.ncbi.nlm.nih.gov/clinvar/variation/2233/

      CAID: CA020148 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.241C%3ET

      gnomAD: 0.0002179 https://gnomad.broadinstitute.org/variant/3-10183772-C-T

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: P81S (c.241C>T) and L188V (c.562C>G)

      MultipleGeneVariants: Germline, VHL, c.562C>G (p.Leu188Val)

      DiseaseEntity:asymptomatic InheritancePattern:AutosomalDominant Ethnicity:German Mutation:Germline ProteinPosition:81 cDNAposition:241 AminoAcidChange:PROtoSER AssumedRefSeq:AF010238.1 MutationType:missense_variant;transition ClinVarID:2233 CAID:CA020148 MultipleVHLVariants FamilyPedigree ClinVarID:Yes Familial CivicName:P81S(c.241C>T)andL188V(c.562C>G) inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    academic-oup-com.proxy1.lib.uwo.ca/jcem/article/87/11/5241/2823479
  123. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Somatic point mutation of the wild-type allele detected in tumors of patients with VHL germline deletion
    1
    1. ClingenBaseline 25 Oct 2026
      not only showed loss of the open-reading frame, but more extended deletions by using c11 and P1 demonstrating complete loss of the VHL gene sequence (>35 kb, but <90 kb)

      PatientID: 2

      KindredID: 2

      Case: Sex Unknown, Age Unknown, Ethnicity Unknown

      DiseaseAssertion: Hemangioblastoma

      FamilyInfo: None

      CasePresentingHPOs: HP:0010797 (Hemangioblastoma)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: deletion (deletion on chromosome 3 (>35kb, <90kb) resulting in complete loss of VHL gene)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: N/A

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: germline deletion on chromosome 3 (>35kb, <90kb) resulting in complete loss of VHL gene. Hemangioblastoma from this patient shows a missense mutation R200W(c.598C>T) in the second copy of VHL gene.

      MutationType: deletion

      CivicName: Deletion AND R200W (c.598C>T)

      MultipleGeneVariants: Somatic, VHL, c.598C>T (p.Arg200Trp)

      DiseaseEntity:hemangioblastoma MultipleVHLVariants CivicName:DELETION MutationType:deletion ClinVarID:N/A NoFamilyInfo ExperimentalAssay Mutation:Germline AssumedRefSeq:NM_000551.3 CivicName:DeletionANDR200W(c.598C>T) UnregisteredVariant inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/11850836/
  124. pubmed-ncbi-nlm-nih-gov.proxy1.lib.uwo.ca pubmed-ncbi-nlm-nih-gov.proxy1.lib.uwo.ca
    Germline mutation profile of the VHL gene in von Hippel-Lindau disease and in sporadic hemangioblastoma
    2
    1. ClingenBaseline 25 Oct 2026

      PatientID: V3

      KindredID: V3

      Case: Sex Unknown, Age Unknown, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: N/A

      CasePresentingHPOs: N/A

      CaseHPOFreeText:N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: 8956040

      SupplementalData: N/A

      Variant: p.R161* (c.481C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 2217 https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: R161* (c.481C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline DiseaseEntity:VHL NoFamilyInfo AssumedRefSeq:NM_000551.3 ProteinPosition:161 CivicName:R161*(c.481C>T) cDNAposition:481 MutationType:stop_gained ClinVarID:2217 ClinVarID:Yes AminoAcidChange:ARGtoTER inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    2. ClingenBaseline 23 Oct 2026

      PatientID: V64

      KindredID: V64

      Case: Sex Unknown, Age Unknown, French

      DiseaseAssertion: VHL

      FamilyInfo: N/A

      CasePresentingHPOs: N/A

      CaseHPOFreeText: Diagnosed with VHL Type 1.

      CaseNotHPOs: HP:0002666 (Pheochromocytoma)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.E73* (c.217C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 223164, https://www.ncbi.nlm.nih.gov/clinvar/variation/223164/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition; stop_gained

      CivicName: E73* (c.217C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:French DiseaseEntity:VHL Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:217 ProteinPosition:73 AminoAcidChange:GLUtoTER ClinVarID:223164 ClinVarID:Yes MutationType:missense_variant;transition MutationType:stop_gained CivicName:E73*(c.217C>T) NoFamilyInfo inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    pubmed-ncbi-nlm-nih-gov.proxy1.lib.uwo.ca/9829912/
  125. www-thieme-connect-de.myaccess.library.utoronto.ca www-thieme-connect-de.myaccess.library.utoronto.ca
    Prevalence and Spectrum of SDHx Mutations in Pheochromocytoma and Paraganglioma in Patients from Belgium: An Update
    1
    1. ClingenBaseline 25 Oct 2026
      The second, H125Y – previously unreported – was associated with the presence of a right pneumogastric nerve PGL diagnosed at 49 years.

      PatientID: N/A

      KindredID: 2

      Case: Sex Unknown, 49Y0M, Ethnicity Unknown

      DiseaseAssertion: Paraganglioma

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0002668 (Paraganglioma)

      CaseHPOFreeText: right pneumogastric nerve paraganglioma

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: SDHD/SDHB/SDHC

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.H125Y (c.373C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVar: 411970 https://www.ncbi.nlm.nih.gov/clinvar/variation/411970/

      CAID: N/A

      gnomAD: 0.00001193 https://gnomad.broadinstitute.org/variant/3-10188230-C-T

      VariantEvidence: N/A

      MutationType: missense_transition

      CivicName: H125Y (c.373C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:paraganglioma Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:373 ProteinPosition:125 AminoAcidChange:HIStoTYR ClinVarID:411970 MutationType:missense_variant;transition CivicName:H125Y(c.373C>T) AgeOfPresentation:paraganglioma:49 ClinVarID:Yes PreviousTesting:SDHD/SDHB/SDHC NoFamilyInfo inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    www-thieme-connect-de.myaccess.library.utoronto.ca/products/ejournals/html/10.1055/s-0032-1311610
  126. erc.bioscientifica.com erc.bioscientifica.com
    Genetics of pheochromocytoma and paraganglioma in Spanish pediatric patients
    1
    1. ClingenBaseline 24 Oct 2026
      510, 17MbPCCLPNEYes (17 years/lung)NoVHLc.499C>T (de novo)bp.(Arg167Gln)No

      PatientID: 5

      KindredID: 7

      Case: M, 17Y0M, Spanish

      DiseaseAssertion: VHL

      FamilyInfo: No family history, assumed de-novo, but unclear if parents were tested to confirm de-novo assertion.

      CohortInfo: 36 pediatric patients with pheochromocytomas and/or parangangliomas.

      CasePresentingHPOs: HP:0002666 (pheochromocytoma)

      CaseHPOFreeText: The patient had a benign bilateral pheochromocytoma that was secreting norepinephrine at age 10. At age 17, the pheochromocytoma reoccured but this time was malignant and metastasized to the lungs.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: RET, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, MAX

      PreviouslyPublished: Yes source unknown.

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T) *The authors of this paper have seemingly called the wrong protein change for this variant.

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 2218 https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954 https://gnomad.broadinstitute.org/variant/3-10191506-C-T

      VariantEvidence: N/A

      MutationType: missense_variant; transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      Mutation:Germline Ethnicity:Spanish DiseaseEntity:VHL PreviousTesting:RET/SDHA/SDHB/SDHC/SDHD/SDHAF2/TMEM127/MAX NonFamilial DiseaseEntity:pheochromocytoma AgeOfPresentation:pheochromocytoma:10 AgeOfPresentation:pheochromocytoma:17 AssumedRefSeq:NM_000551.3 CivicName:R167W(c.499C>T) cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP ClinVarID:2218 ClinVarID:Yes MutationType:missense_variant;transition InheritancePattern:DeNovoAssertion inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    erc.bioscientifica.com/view/journals/erc/20/3/L1.xml
  127. www.nejm.org www.nejm.org
    Germ-Line Mutations in Nonsyndromic Pheochromocytoma | NEJM
    1
    1. ClingenBaseline 24 Oct 2026

      PatientID: N/A

      KindredID: 21

      Case: Sex, Age, Ethnicity Unknown

      DiseaseAssertion: pheochromocytoma

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0002666 (pheochromocytoma)

      CaseHPOFreeText: Nonsyndromic pheochromocytoma.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: RET, SDHB, SDHD

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.Q195* (c.583C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: p.Q195* (c.796C>T)

      ClinVarID: 428794 https://www.ncbi.nlm.nih.gov/clinvar/variation/428794/

      CAID: CA70052558 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.583C%3ET

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: Q195* (c.583C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline DiseaseEntity:pheochromocytoma AssumedRefSeq:AF010238.1 MutationType:stop_gained ProteinPosition:195 CivicName:Q195*(c.583C>T) cDNAposition:583 AminoAcidChange:GLNtoTER ClinVarID:428794 ClinVarID:Yes PreviousTesting:RET/SDHB/SDHD NoFamilyInfo inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    nejm.org/doi/10.1056/NEJMoa020152
  128. www.scielo.br www.scielo.br
    Molecular analysis of the Von Hippel-Lindau (VHL) gene in a family with non-syndromic pheochromocytoma: the importance of genetic testing
    1
    1. ClingenBaseline 24 Oct 2026
      One year later, a 10-year-old sister of the proband (II-2) was referred to our service because of palpitations, weight loss, diaphoresis, and shooting pain attacks that had started about two weeks earlier. Based on this clinical picture and because of her family history, a pheochromocytoma was suspected immediately. Her urinary metanephrines were elevated to 12.2 mg/g creatinine (< 1 mg/g). A CT of the abdomen revealed a mass in the left adrenal; there were no lesions in the pancreas or the kidney. This mass was also positive on MIBG scintigraphy. As in her brother, there was no suggestion that the paraganglia would also be involved. Her MRI of the brain, and her echocardiogram were both normal. She was then treated with an alpha-blocker (prazosin) in preparation for an open adrenalectomy. Histology and immunohistochemistry confirmed diagnosis of a pheochromocytoma in the left adrenal gland.

      PatientID: II-2

      KindredID: 1

      Case: F, 10Y0M, Ethnicity Unknown

      DiseaseAssertion: Adrenal pheochromoyctoma

      FamilyInfo: The patient’s brother (II-1) was found to harbor the same germline mutation the patient harbored and had bilateral adrenal pheochromocytoma at 14Y. The same germline missense mutation was detected in another sister (II-4) with right adrenal pheochromocytoma and her asymptomatic daughter (III-1). The father was not available for genetic testing because he had died, apparently secondary to a hypertensive crisis. The five other family members which underwent genetic testing did not have the mutation.

      CasePresentingHPOs: HP:0006748 (Adrenal pheochromocytoma)

      CaseHPOFreeText: At 10Y, the patient reported palpitations, weight loss, diaphoresis, and shooting pain attacks. Her urinary metanephrines were elevated to 12.2 mg/g creatinine. A CT of the abdomen revealed a mass in the left adrenal gland. Histology and immunohistochemistry confirmed diagnosis of left adrenal pheochromocytoma. Additional screening revealed no other tumours, so this fit the criteria of VHL type 2C.

      CaseNotHPOs: HP:0002668; HP:0012090; HP:0012210 (Paraganglioma, abnormal pancreas morphology, abnormal renal morphology)

      CaseNotHPOFreeText: There were no lesions in the pancreas or the kidney, there was also no suggestion that the paraganglia would also be involved. Her MRI of the brain, and her echocardiogram were both normal.

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.V166F (c.496G>T)

      LegacyVariant: N/A

      ClinVarID: 2224, https://www.ncbi.nlm.nih.gov/clinvar/variation/2224/

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: V166F(c.496G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:adrenalpheochromocytoma AgeOfPresentation:adrenalpheochromocytoma:10 Mutation:Germline RefSeq:N/A AssumedRefSeq:NM_000551.3 cDNAposition:496 ProteinPosition:166 ClinVarID:Yes MutationType:missense_variant;transversion CivicName:V166F(c.496G>T) FamilyPedigree Familial AminoAcidChange:VALtoPHE ClinVarID:2224 inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    scielo.br/j/abem/a/MbLMTLsfq6jvN3HLJt5qZHH/
  129. eje.bioscientifica.com eje.bioscientifica.com
    Germline VHL gene mutations in Hungarian families with von Hippel–Lindau disease and patients with apparently sporadic unilateral pheochromocytomas
    1
    1. ClingenBaseline 24 Oct 2026
      BIP–27–19Renal cysts, pancreatic cysts, and polyglobulia1

      PatientID: None

      KindredID: B

      Case: M, 27Y0M, Hungarian

      DiseaseAssertion: VHL

      FamilyInfo: The parents of the patient rejected clinical and genetic screening, whereas clinical screening in a younger brother of the index patient revealed no abnormality.

      CasePresentingHPOs: HP:0009711, HP:0000107, HP:0001737, HP:0001901, HP:0006880 (retinal capillary hemangioma, renal cyst, pancreatic cysts, polycythemia, cerebellar hemangioblastoma)

      CaseHPOFreeText: Retina involvement presented at age 19. The patient had cerebellar hemangioma as well as renal and pancreatic cysts at the age of 27 years.

      CaseNotHPOs: HP:0005584, HP:0002666 (renal cell carcinoma, pheochromocytoma)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R161* (c.481C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 2217 https://www.ncbi.nlm.nih.gov/clinvar/variation/2217/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: R161* (c.481C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL Mutation:Germline Ethnicity:Hungarian AssumedRefSeq:NM_000551.3 NoFamilyInfo DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:renalcyst DiseaseEntity:pancreaticcysts DiseaseEntity:polycythemia DiseaseEntity:cerebellarhemangioblastoma AgeOfPresentation:RetinalCapillaryHemangioma:19 AgeOfPresentation:cerebellarhemangioblastoma:27 AgeOfPresentation:renalcyst:27 AgeofPresentation:pancreaticcysts:27 CivicName:R161*(c.481C>T) cDNAposition:481 ProteinPosition:161 MutationType:stop_gained ClinVarID:2217 ClinVarID:Yes AminoAcidChange:ARGtoTER inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    eje.bioscientifica.com/view/journals/eje/161/3/495.xml
  130. onlinelibrary-wiley-com.proxy1.lib.uwo.ca onlinelibrary-wiley-com.proxy1.lib.uwo.ca
    von Hippel-Lindau development in children and adolescents
    1
    1. ClingenBaseline 24 Oct 2026
      15 I 6 23 No manifestations M c.496G > T (p.Val166Phe)

      PatientID: I

      KindredID: 15

      Case: Sex Unknown, 23Y0M, Danish

      DiseaseAssertion: Asymptomatic

      FamilyInfo: 2 other family members presented with the same VHL variant. Patient 15-II presented with 2 pheochromocytoma (8Y) 2 CNS hb (12Y and 13Y) and 2 retinal hemangioblastomas (8Y, 12Y). Patient 15-III presented with 2 pheochromocytoma (15Y).

      CasePresentingHPOs: N/A

      CaseHPOFreeText: Diagnosed with VHL at age 6Y. Age at the end of study: 23Y.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.V166F (c.496G>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2224, https://www.ncbi.nlm.nih.gov/clinvar/variation/2224/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: V166F (c.496G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Danish DiseaseEntity:VHL DiseaseEntity:asymptomatic Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:496 ProteinPosition:166 AminoAcidChange:VALtoPHE ClinVarID:2224 ClinVarID:Yes MutationType:missense_variant;transversion CivicName:V166F(c.496G>T) Familial inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    onlinelibrary-wiley-com.proxy1.lib.uwo.ca/doi/10.1002/ajmg.a.38324
  131. onlinelibrary.wiley.com onlinelibrary.wiley.com
    Genetic analysis of von Hippel-Lindau disease
    1
    1. ClingenBaseline 24 Oct 2026

      PatientID: N/A

      KindredID: 442

      Case: Age unknown, Sex unknown, Ethnicity unknown

      DiseaseAssertion: assumed VHL

      FamilyInfo: Paper states: Germline, de novo (no clear confirmation)

      CasePresentingHPOs: HP:0005584; HP:0010797 (renal cell carcinoma, hemangioblastoma)

      CaseHPOFreeText: Bilateral RCC and a hemangioblastoma

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: Yes (Specifically Supp. Table S2)

      Variant: p.G144* (c.430G>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 223208 https://www.ncbi.nlm.nih.gov/clinvar/variation/223208/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: G144* (c.430G>T)

      MultipleGeneVariants: N/A

      Mutation:Germline RefSeq:NM_000551.2 DiseaseEntity:VHL InheritancePattern:DeNovoAssertion DiseaseEntity:renalcellcarcinoma DiseaseEntity:hemangioblastoma CivicName:G144*(c.430G>T) cDNAposition:430 ProteinPosition:144 MutationType:stop_gained AminoAcidChange:GLYtoTER ClinVarID:223208 ClinVarID:Yes NonFamilial ExperimentalAssay SupplementalData inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    onlinelibrary.wiley.com/doi/abs/10.1002/humu.21219
  132. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Functioning Mediastinal Paraganglioma Associated with a Germline Mutation of von Hippel-Lindau Gene
    1
    1. ClingenBaseline 24 Oct 2026
      her 17-year-old sister

      PatientID: None

      KindredID: 1

      Case: F, 17Y0M, Ethnicity Unknown

      DiseaseAssertion: Retinal hemangioblastoma

      FamilyInfo: The heterozygous missense variant NM_000551.3:c.311G>T was identified on her 21-year-old sister and her mother, but not her father. The sister had hypertension and a paraganglioma. The patient’s mother had refused a complete staging.

      CasePresentingHPOs:HP:0009711 (Retinal hemangioblastoma)

      CaseHPOFreeText: The patient’s evaluation was normal with the exception of a small retinal hemangioblastoma.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.G104V(c.311G>T)

      LegacyVariant: N/A

      ClinVarID: 223183, http://www.ncbi.nlm.nih.gov/clinvar/variation/223183

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: G104V(c.311G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:retinalcapillaryhemangioma AgeOfPresentation:retinalcapillaryhemangioma:17 Mutation:Germline RefSeq:NM_000551.3 cDNAposition:311 ProteinPosition:104 CivicName:G104V(c.311G>T) AminoAcidChange:GLYtoVAL ClinVarID:Yes ClinVarID:223183 MutationType:missense_variant;transversion Familial inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC6025296/
  133. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Molecular Genetic Diagnosis of von Hippel‐Lindau Disease: Analysis of Five Japanese Families
    1
    1. ClingenBaseline 24 Oct 2026
      three familial cases

      PatientID: 8

      KindredID: C

      Case: M, Age Unknown, Japanese

      DiseaseAssertion: Asymptomatic

      FamilyInfo: This mutation was found in a family of 10 individuals; six were found to carry the mutation NM_000551.3:c.464-1G>T the patient carried, and three presented with symptoms. They were identified with hemangioblastomas of the central nervous system and retinal angiomas. The eldest patient also had renal cell carcinoma (patient C-1).

      CasePresentingHPOs: N/A

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: (c.464-1G>T)

      LegacyVariant: (c.677-1G>T)

      ClinVarID: 223221, http://www.ncbi.nlm.nih.gov/clinvar/variation/223221

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: splice_site_variant

      CivicName: SpliceSite(c.464-1G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Japanese DiseaseEntity:asymptomatic Mutation:Germline RefSeq:N/A ProteinPosition:N/A AminoAcidChange:N/A ClinVarID:Yes ClinVarID:223221 MutationType:splice_site_variant FamilyPedigree Familial CivicName:SpliceSite(c.464-1G>T) cDNAposition:464 AssumedRefSeq:AF010238.1 inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC5921130/
  134. erc.bioscientifica.com erc.bioscientifica.com
    Paediatric pancreatic neuroendocrine tumours in von Hippel–Lindau disease
    1
    1. ClingenBaseline 24 Oct 2026
      and 9

      PatientID: None

      KindredID: 1

      Case: F, 9Y0M, Ethnicity Unknown

      DiseaseAssertion: Asymptomatic

      FamilyInfo: This patient had an older brother who at 7-years-old, presented with multiple retinal haemangiomas. At the age of 9, he underwent a left adrenalectomy for a phaeochromocytoma. At the age of 13, a 9 mm solid lesion consistent with a pNET. This patient also had a renal cell carcinoma. They also had a 12-year old younger brother who had a retinal hemangioma. The patients father was diagnosed with VHL at 31 years-old and had multiple cerebellar haemangioblastomas, retinal angiomas, a phaeochromocytoma, a ccRCC and a small pNET. Pedigree: See Figure 1.

      CasePresentingHPOs: N/A

      CaseHPOFreeText: N/A

      CaseNotHPOs: HP:0002666, HP:0005584, HP:0009711, HP:0030405 (pheochromocytoma, renal cell carcinoma, Retinal capillary hemangioma, Pancreatic endocrine tumor)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.Arg120* (c.358A>T)

      LegacyVariant: N/A

      ClinVarID: N/A

      CAID: CA351753732 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA351753732

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: stop_gained

      CivicName: R120*(c.358A>T)

      MultipleGeneVariants: N/A

      DiseaseEntity:asymptomatic InheritancePattern:AutosomalDominant AssumedRefSeq:NM_000551.3 cDNAposition:358 AminoAcidChange:ARGto* CAID:CA351753732 MutationType:stop_gained CivicName:R120*(c.358A>T) Mutation:Germline ProteinPosition:120 ClinVarID:N/A Familial FamilyPedigree inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    erc.bioscientifica.com/view/journals/erc/25/9/ERC-18-0123.xml
  135. journals.lww.com journals.lww.com
    Endocrine Pancreatic Tumors in von Hippel-Lindau Disease:... : Pancreas
    1
    1. ClingenBaseline 24 Oct 2026
      5 nonsense mutations

      PatientID: 30

      KindredID: 64

      Case: Sex unknown, Age unknown, French

      DiseaseAssertion: VHL

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0005584; HP:0030405 (renal cell carcinoma, pancreatic endocrine tumour)

      CaseHPOFreeText: N/A

      CaseNotHPOs: HP:0002666 (pheochromocytoma)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.Q73* (c.217C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 223164 https://www.ncbi.nlm.nih.gov/clinvar/variation/223164/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence:N/A

      MutationType: stop_gained

      CivicName: Q73* (c.217C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:French Mutation:Germline DiseaseEntity:VHL DiseaseEntity:renalcellcarcinoma DiseaseEntity:pancreaticendocrinetumor CivicName:Q73*(c.217C>T) cDNAposition:217 ProteinPosition:73 AminoAcidChange:GLNtoTER MutationType:stop_gained ClinVarID:223164 ClinVarID:Yes NoFamilyInfo AssumedRefSeq:NM_000551.3 inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    journals.lww.com/pancreasjournal/fulltext/2008/07000/endocrine_pancreatic_tumors_in_von_hippel_lindau.13.aspx
  136. academic.oup.com academic.oup.com
    Pheo-Type: A Diagnostic Gene-expression Assay for the Classification of Pheochromocytoma and Paraganglioma
    1
    1. ClingenBaseline 24 Oct 2026
      VCB.14T VHL VHL 0.63 

      PatientID: VCB.14T

      KindredID: 6

      Case: Sex Unknown, 34Y0M, Ethnicity Unknown

      DiseaseAssertion: pheochromocytoma

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0002668; HP:0002666 (paraganglioma, pheochromocytoma)

      CaseHPOFreeText: Presented with bilateral pheochromocytoma

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: MAX, RET, SDHA, SDHB, SDHC, SDHD, TMEM127

      PreviouslyPublished: 25545346 (see table S1 and S10)

      SupplementalData: Yes

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T?dataset=gnomad_r2_1

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: SDHA, Germline, c.619A>C (p.Arg207=); SDHA, Germline, c.1969G>A (p.Val657Ile); KIF1B, Germline, c.2192A>G (p.Asn777Ser); MDH2, Somatic, c.26C>T (p.Ala9Val)

      InheritancePattern:AutosomalDominant DiseaseEntity:pheochromocytoma DiseaseEntity:paraganglioma Mutation:Germline RefSeq:NM_000551.3 ProteinPosition:167 cDNAposition:499 CivicName:R167W(c.499C>T) MutationType:missense_variant;transition ClinVarID:2218 ClinVarID:Yes ExperimentalAssay SupplementalData NoFamilyInfo AminoAcidChange:ARGtoTRP MultipleGeneVariants PreviousTesting:MAX/RET/SDHA/SDHB/SDHC/SDHD/TMEM127 inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    academic.oup.com/jcem/article/101/3/1034/2804853
  137. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    ajhg00053-0036.pdf
    1
    1. ClingenBaseline 23 Oct 2026
      D2,

      Case#: Patient D2, Druze religious group, located in lower Galilee.

      DiseaseAssertion: MPS1-H

      FamilyInfo: N/A

      CasePresentingHPOs: N/A

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CaseEnzymeAssay: N/A

      CaseUrineGAGs: N/A

      CaseERT: N/A

      CaseBMT: N/A

      Variant1: c.928C>T (p.Q310X)

      Variant1ClinVarID: 11915

      Variant1CAID: N/A

      Variant2: N/A

      Variant2ClinVarID: N/A

      Variant2CAID: N/A

      AdditionalVariants: N/A

      ParentalGenotype: N/A

      PreviouslyPublished N/A

      Gene:IDUA CaseInfo c.928C>T ClinVarID:11915 DiseaseEntity:MPS1 inferred_gene_hgnc:5391 inferred_gene_source:Gene_Name IDUA variant annotation
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    pmc.ncbi.nlm.nih.gov/articles/instance/1682364/pdf/ajhg00053-0036.pdf
  138. www-sciencedirect-com.proxy1.lib.uwo.ca www-sciencedirect-com.proxy1.lib.uwo.ca
    Clinical and genetic analysis of patients with pancreatic neuroendocrine tumors associated with von Hippel-Lindau disease
    1
    1. ClingenBaseline 23 Oct 2026
      2550Fnt 658 G to T, Ala to SerR, 26012

      PatientID: 25

      KindredID: 6012

      Case: F, 50Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: Another member of her family, (patient 26) presented with one radiologic pancreatic neuroendocrine tumor and had the same VHL gene mutation.

      CasePresentingHPOs: HP:0030405 (pancreatic endocrine tumour)

      CaseHPOFreeText: She presented with two radiologic pancreatic endocrine tumour.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.A149S (c.445G>T)

      LegacyVariant: p.A149S (c.658G>T)

      CaseProblemVariantFreeText: N/A

      ClinVar:127829 https://www.ncbi.nlm.nih.gov/clinvar/variation/127829/

      CAID: CA020355 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.445G%3ET

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: A149S (c.445G>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:pancreaticendocrinetumor AgeOfPresentation:pancreaticendocrinetumor:50 AssumedRefSeq:AF010238.1 Mutation:Germline MutationType:missense_variant;transversion ClinVarID:127829 CAID:CA020355 CivicName:A149S(c.445G>T) Familial cdnaposition:445 ProteinPosition:149 AminoAcidChange:ALAtoSER ClinVarID:Yes inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    www-sciencedirect-com.proxy1.lib.uwo.ca/science/article/pii/S0039606000070100
  139. academic.oup.com academic.oup.com
    Molecular Dissection of the VHL Gene in Solitary Capillary Hemangioblastoma of the Central Nervous System
    1
    1. ClingenBaseline 23 Oct 2026
      HGB-19 B/T Germline 2 2 c.341 G > T G114V This study R No  

      PatientID: HGB-19

      KindredID: 4

      Case: Sex Unknown, 44Y0M, Italian

      DiseaseAssertion: VHL

      FamilyInfo: None.

      CohortInfo: The patient cohort consisted of 57 patients (26 male and 31 female) from Southern Italy, most of whom (55 of 57) presented with solitary HGB of the CNS: 6 were syndromic and 51 were apparently sporadic.

      CasePresentingHPOs: HP:0006880, HP:0009713 (cerebellar hemangioblastoma, spinal hemangioblastoma)

      CaseHPOFreeText: The patient had a single cerebellar hemangioblastoma that was diagnosed at age 32. The patient had a spinal cord hemangioblastoma at age 40.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.G114V(c.341G>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: N/A

      CAID: CA351753604 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.341G%3ET

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transversion

      CivicName: G114V (c.341G>T)

      MultipleGeneVariants: N/A

      MutationType:missense_variant;transversion InheritancePattern:AutosomalDominant Mutation:Germline RefSeq:NM_000551.3 Ethnicity:Italian DiseaseEntity:VHL NonFamilial DiseaseEntity:cerebellarhemangioblastoma DiseaseEntity:spinalhemangioblastoma AgeOfPresentation:cerebellarhemangioblastoma:32 AgeOfPresentation:spinalhemangioblastoma:40 cDNAposition:341 ProteinPosition:114 AminoAcidChange:GLYtoVAL ClinVarID:N/A CAID:CA351753604 CivicName:G114V(c.341G>T) inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    academic.oup.com/jnen/article-abstract/73/1/50/2917595
  140. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    The incidence of consecutive manifestations in Von Hippel-Lindau disease
    1
    1. ClingenBaseline 23 Oct 2026
       c.499C > T1 (1%)2a/b43HBr, HBsc, RCC, Pheo, Cr

      PatientID: None

      KindredID: 13

      Case: Sex Unknown, 43Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: N/A

      CohortInfo: All VHL mutation carriers of 18 years or older who underwent surveillance according to Dutch VHL guidelines between 1972 and 2012 in the VHL expertise centers University Medical Center Groningen (UMCG) and University Medical Center Utrecht (UMCU) were included. Patients with VHL-disease subtype 2C (pheochromocytoma only) were excluded.

      CasePresentingHPOs: HP:0009711; HP:0009713; HP:0005584; HP:0000107; HP:0002666 (Retinal capillary hemangioma, Spinal hemangioblastoma, Renal cell carcinoma, Renal cyst, Pheochromocytoma)

      CaseHPOFreeText: VHL Type 2a/b.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: 24132471

      SupplementalData: Table 1

      Variant: p.R167W (c.499C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2218, https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954, https://gnomad.broadinstitute.org/variant/3-10191506-C-T

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:spinalhemangioblastoma DiseaseEntity:renalcellcarcinoma DiseaseEntity:renalcyst DiseaseEntity:pheochromocytoma Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP ClinVarID:2218 ClinVarID:Yes MutationType:missense_variant;transition CivicName:R167W(c.499C>T) NoFamilyInfo SupplementalData inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC6560011/
  141. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Pedigree analysis, diagnosis and treatment in Von Hippel-Lindau syndrome: A report of three cases
    1
    1. ClingenBaseline 23 Oct 2026
      MRI of the brain of the patient's brother (II-3) indicated a nodule in the left cerebellar tonsil with a size of ~9.0×10.5 mm, which indicated the presence of a hemangioblastoma, astrocytoma or ependymoma. However, the diagnosis could not be confirmed. Therefore, patient II-3 was regarded as a carrier of the mutant gene.

      PatientID:II-3

      KindredID: 2

      Case: M, Sex Unknown, Chinese

      DiseaseAssertion:Asymptomatic

      FamilyInfo: The mother of the patient (I-2) was deceased, and the cause was unknown. The mother exhibited a brain tumor and coronary heart disease whilst alive. Multiple nodules were detected in the thyroid gland of the patient's eldest sister (II-1), but were not treated. Another sister (II-2) also had the mutation but was asymptomatic. See Figure 2 for pedigree.

      CasePresentingHPOs: N/A

      CaseHPOFreeText: MRI of the brain of the patient's brother (II-3) indicated a nodule in the left cerebellar tonsil with a size of ~9.0×10.5 mm, which indicated the presence of a hemangioblastoma, astrocytoma or ependymoma. However, the diagnosis could not be confirmed.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.R167W (c.499C>T)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 2218 https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/

      CAID: N/A

      gnomAD: 0.000007954 https://gnomad.broadinstitute.org/variant/3-10191506-C-T

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167W (c.499C>T)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline AssumedRefSeq:NM_000551.3 DiseaseEntity:asymptomatic Familial FamilyPedigree Ethnicity:Chinese CivicName:R167W(c.499C>T) cDNAposition:499 ProteinPosition:167 AminoAcidChange:ARGtoTRP ClinVarID:2218 ClinVarID:Yes MutationType:missense_variant;transition inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC5876499/
  142. onlinelibrary-wiley-com.uhn.idm.oclc.org onlinelibrary-wiley-com.uhn.idm.oclc.org
    The genomic landscape of phaeochromocytoma
    1
    1. ClingenBaseline 23 Oct 2026
      All germline mutations in VHL,

      PatientID: V-PH-05T

      KindredID: 3

      Case: F, 27Y0M, Ethnicity Unknown

      DiseaseAssertion: assumed VHL

      FamilyInfo: No familial cancers/syndromic illnesses

      CasePresentingHPOs: HP:0002666; HP:0009711 (pheochromocytoma, retinal capillary hemangioma)

      CaseHPOFreeText: diagnosed with recurrent phaeochromocytoma at age 12Y, surgery at 27Y. She also had a personal history of angioma of the right eye, laparotomy & numerous thyrocotomies, and a history of hypertension. Presence of elevated catecholamines, but no further details.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: RET, SDHA, SDHB, SDHC, TMEM127

      PreviouslyPublished: 26796762

      SupplementalData: Yes (see table S1 and S10)

      Variant: p.T157I (c.470C>T)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: Stated as ENSP00000256474.2:p.Thr157Ile

      ClinVarID: 223223 https://www.ncbi.nlm.nih.gov/clinvar/variation/223223/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: T157I (c.470C>T)

      MultipleGeneVariants: Germline, SDHA, c.113A>T (p.Asp38Val)

      InheritancePattern:AutosomalDominant DiseaseEntity:pheochromocytoma DiseaseEntity:retinalcapillaryhemangioma AgeOfPresentation:pheochromocytoma:12 NonFamilial Mutation:Germline AssumedRefSeq:NM_000551.3 ProteinPosition:157 CivicName:T157I(c.470C>T) cDNAposition:470 AminoAcidChange:THRtoILE MutationType:missense_variant;transition ClinVarID:223223 ClinVarID:Yes SupplementalData MultipleGeneVariants PreviousTesting:RET/SDHA/SDHB/SDHC/TMEM127 inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    onlinelibrary-wiley-com.uhn.idm.oclc.org/doi/full/10.1002/path.4503