6 Matching Annotations
  1. Last 7 days
  2. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Genotype-phenotype correlations in Chinese von Hippel–Lindau disease patients
    1
    1. ClingenBaseline 02 Nov 2026

      PatientID: 97

      KindredID: 33

      Case: M, 37Y0M, Chinese

      DiseaseAssertion: VHL

      FamilyInfo: The proband (patient 97) presented with a CNS hemangioblastoma at 37, retinal angioma at 20, and renal cell carcinoma and multiple pancreatic cysts/tumors at age 29. Their brother, patient 98, presented with a retinal angioma at age 32, and at age 43 presented with renal cell carcinoma and multiple pancreatic cysts/tumors.

      CasePresentingHPOs: HP:0010797; HP:0001732; HP:0001737; HP:0005584; HP:0009711 (Hemangioblastoma, Abnormality of the pancreas, Pancreatic cysts, Renal cell carcinoma, Retinal capillary hemangioma)

      CaseHPOFreeText: The proband, patient 291, presented with a CNS hemangioblastoma at 27, and at 31 presented with renal cell carcinoma, multiple pancreatic cysts/tumors, and pheochromocytoma.

      CaseNotHPOs: HP:0002666 (Pheochromocytoma)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: This cohort 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.P97Afs*35 (c.287_288insA)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: N/A

      CAID: CA432420510, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.287_288insA

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: plus_1_frameshift_variant

      CivicName: P97Afs*35 (c.287_288insA)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Chinese Mutation:Germline AssumedRefSeq:NM_000551.3 DiseaseEntity:VHL DiseaseEntity:hemangioblastoma DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:renalcellcarcinoma DiseaseEntity:abnormalityofthepancreas DiseaseEntity:pancreaticcysts AgeOfPresentation:hemangioblastoma:37 AgeOfPresentation:retinalcapillaryhemangioma:20 AgeOfPresentation:renalcellcarcinoma:29 AgeOfPresentation:pancreaticcysts:29 AgeOfPresentation:abnormalityofthepancreas:29 MutationType:plus_1_frameshift_variant ClinVarID:N/A CAID:CA432420510 Familial SupplementalData cDNAposition:287 ProteinPosition:97 AminoAcidChange:PROtoALA CivicName:P97Afs*35(c.287_288insA) inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC5503545/
  3. www.cancerjournal.net www.cancerjournal.net
    Adrenal adenoma in von Hippel–Lindau syndrome: A case report with review of literature
    1
    1. ClingenBaseline 31 Oct 2026
      A 29-year-old hypertensive male with genetic proven VHL syndrome came to the Endocrinology department for evaluation. There was neither any history of paroxysm of sweating or palpitation nor any stigmata of hypercortisolism. He had undergone surgery for cervical (C2–C3) hemangioblastoma 2 years back. His elder sister also had features suggestive of Type 1 VHL syndrome (cerebellar hemangioblastomas, RCC of the left kidney, bilateral renal cysts, and pancreatic serous cystic neoplasm). However, her adrenal glands were normal. None of the other family members have features suggestive of VHL syndrome.Noncontrast computed tomography of the abdomen of our patient revealed a well-defined hypodense (<10 Hounsfield Unit) lesion of 3.2 cm × 3 cm in the left adrenal gland having central necrosis. There was more than 50% washout in postcontrast delayed image suggestive of adrenal adenoma [Figure 1]. In bilateral kidneys, there were multiple hypodense lesions with intense enhancement (RCC) along with nonenhancing cystic areas (renal cysts). Pancreas also showed multiple well-defined fluid attenuating cysts. On hormonal evaluation, plasma-free metanephrine (51.1 pg/ml; Normal < 65 pg/ml) and free normetanephrine (87.3 pg/ml; Normal < 180 pg/ml) levels were within normal limits. Serum dehydroepiandrosterone sulfate (267 μg/dl; Normal 167–591 μg/dl) and electrolytes were also normal. Normal values of 8 am serum cortisol (16.89 μg/dl), midnight awake cortisol (1.96 μg/dl) and overnight 1 mg dexamethasone suppression test (0.81 μg/dl) ruled out the possibility of endogenous hypercortisolism. Although biochemically there was no evidence of pheochromocytoma, metaiodobenzylguanidine (MIBG) scintigraphy was done on high suspicion of it for an adrenal mass in an established case of VHL. However, MIBG scan failed to show any abnormal tracer uptake in the abdomen.Figure 1: Computed tomography scan of adrenal adenoma. (a) Plain computed tomography abdomen showing homogenous, well defined left adrenal mass. (b) Early postcontrast image showing peripheral enhancement of the left adrenal mass. (c) Delayed postcontrast image showing more than 50% washout of contrastClick here to viewThen, the patient underwent left-sided adrenalectomy after controlling hypertension. On gross examination of the adrenal mass, an encapsulated gray-brown lesion measuring 3 cm × 3 cm × 3 cm in size with areas of hemorrhage was found. On microscopic examination, the tumor cells with clear cytoplasm were arranged in a nesting pattern [Figure 2]a. There was no significant atypia of the tumor cells and mitotic figures were also absent. On immunohistochemistry, the tumor cells were positive for Inhibin and Melan A [Figure 2]b and [Figure 2]c and negative for synaptophysin, thereby confirming adrenocortical adenoma and excluding pheochromocytoma. The adjacent adrenal gland was normal. For the largest focus of RCC, right-sided partial nephrectomy was done 3 months later. On histopathological examination, the tumor was circumscribed and measured 4 cm × 3 cm × 2 cm in dimensions. The cut section showed areas of hemorrhage and congestion without any areas of necrosis. On microscopy, the tumor had a sharp demarcation from normal parenchyma and the renal capsule without any evidence of infiltration [Figure 3]a. The tumor cells had minimal atypia, abundant clear/vacuolated cytoplasm, low nuclear grade, and rare mitosis. The morphological features were compatible with the clear cell type of RCC [Figure 3]b.Figure 2: Histopathology of adrenal tumor. (a) H and E stain (×200) of adrenal tumor showing tumor cells with clear cytoplasm arranged in a nesting pattern. (b) Immunohistochemistry of Melan A (×100) of adrenal tumor showing diffuse cytoplasmic positivity in tumor cells. (c) Immunohistochemistry of Inhibin (×100) of adrenal tumor showing strong cytoplasmic positivity in tumor cellsClick here to viewFigure 3: Histopathology of renal tumor. (a) The low magnification image (H and E stain ×100) of renal tumor shows the sharp demarcation between the tumor (left side) and adjacent normal renal parenchyma (right side). (b) The high magnification image (H and E ×400) of renal tumor shows the tumor cells with clear cytoplasm, low nuclear grade, intricate capillary network and lakes of red blood cellsClick here to viewGenetic analysis of VHL gene in this patient revealed a heterogeneous 5' splice site variation of intron 1 of the VHL gene that affects splice site of exon 1 (c. 340 + 1G > A). This mutation was pathogenic for VHL syndrome and previously reported in a few cases.[4],[5],[6]

      PatientID: None

      KindredID: 1

      Case: M, 29Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: His elder sister also had features suggestive of Type 1 VHL syndrome (cerebellar hemangioblastomas, RCC of the left kidney, bilateral renal cysts, and pancreatic serous cystic neoplasm). However, her adrenal glands were normal. None of the other family members have features suggestive of VHL syndrome.

      CasePresentingHPOs: HP:0009713; HP:0000822; HP:0006770; HP:0005562; HP:0001737; HP:0008256 (Spinal Hemangioblastoma, Hypertension, Clear cell renal cell carcinoma, Multiple renal cysts, Pancreatic cysts, Adrenocortical adenoma)

      CaseHPOFreeText: CT of the abdomen revealed a lesion in the left adrenal gland having central necrosis. There was more than 50% washout in postcontrast delayed image suggestive of adrenal adenoma (later confirmed by immunohistochemistry to be an adrenocortical adenoma). In bilateral kidneys, there were multiple lesions with intense enhancement (RCC - morphological features were compatible with the clear cell type of RCC) along with nonenhancing cystic areas (renal cysts). Pancreas also showed multiple well-defined fluid attenuating cysts.

      CaseNotHPOs: HP:000266; HP:0001962; HP:0003118; HP:0001069 (Pheochromocytoma, Palpitations, Increased circulating cortisol level, Episodic hyperhidrosis)

      CaseNotHPOFreeText: No history of paroxysm of sweating or palpitation nor any stigmata of hypercortisolism. Immunochemistry excluded the possibility of the adrenal lesion being pheochromocytoma.

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: c.340+1G>A

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 223190, https://www.ncbi.nlm.nih.gov/clinvar/variation/223190/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: splice_site_variant

      CivicName: Splice Site (c.340+1G>A)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:VHL DiseaseEntity:clearcellrenalcellcarcinoma DiseaseEntity:spinalhemangioblastoma DiseaseEntity:multiplerenalcysts DiseaseEntity:pancreaticcysts DiseaseEntity:hypertension DiseaseEntity:adrenocorticaladenoma AgeOfPresentation:clearcellrenalcellcarcinoma:29 AgeOfPresentation:pancreaticcysts:29 AgeOfPresentation:multiplerenalcysts:29 AgeOfPresentation:hypertension:29 AgeOfPresentation:adrenocorticaladenoma:29 Mutation:Germline AssumedRefSeq:NM_000551.3 ProteinPosition:N/A AminoAcidChange:N/A ClinVarID:223190 ClinVarID:Yes MutationType:splice_site_variant CivicName:SpliceSite(c.340+1G>A) Familial cDNAposition:N/A inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    cancerjournal.net/article.asp
  4. Oct 2026
  5. cancerres.aacrjournals.org cancerres.aacrjournals.org
    Telomere Shortening Is Associated with Genetic Anticipation in Chinese Von Hippel–Lindau Disease Families
    1
    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
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    cancerres.aacrjournals.org/content/74/14/3802
  6. 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 29 Oct 2026
      missense mutations (1/16)

      PatientID: 6

      KindredID: 6

      Case: 29Y0M, Sex Unknown, Argentinian

      DiseaseAssertion: VHL

      FamilyInfo: Positive family history

      CasePresentingHPOs: HP:0010797; HP:0009711; HP:0001737; HP:0000107 (hemangioblastoma; retinal capillary hemangioma; pancreatic cysts; renal cysts)

      CaseHPOFreeText: Aged 22Y at diagnosis (genetic testing); fulfils type 1 VHL clinical diagnosis. CNS and retinal hemangioblastoma was diagnosed at 22, pancreatic cysts and renal cysts were diagnosed at 29Y (See Table 1 & 2).

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: absence of pheochromocytoma/paraganglioma (pheo/pgl) after 14 years of follow-up.

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.C162W (c.486C>G)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 223227 https://www.ncbi.nlm.nih.gov/clinvar/variation/223227/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transversion

      CivicName: C162W (c.486C>G)

      MultipleGeneVariants: N/A

      Ethnicity:Argentinian DiseaseEntity:VHL Familial ClinVarID:Yes ClinVarID:223227 MutationType:missense_variant;transversion CivicName:C162W(c.486C>G) cDNAposition:486 ProteinPosition:162 AminoAcidChange:CYStoTRP DiseaseEntity:hemangioblastoma DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:pancreaticcysts DiseaseEntity:renalcyst AgeOfPresentation:pancreaticcysts:29 AgeOfPresentation:renalcyst:29 AgeOfPresentation:hemangioblastoma:22 AgeOfPresentation:retinalcapillaryhemangioma:22 Mutation:Germline RefSeq:NM_000551.3 ExperimentalAssay inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    liebertpub.com/doi/10.1089/gtmb.2016.0204
  7. 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/
  8. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Genotype-phenotype correlations in Chinese von Hippel–Lindau disease patients
    1
    1. ClingenBaseline 24 Oct 2026

      PatientID: 208

      KindredID: 79

      Case: M, 49Y0M, Chinese

      DiseaseAssertion: VHL

      FamilyInfo: The proband's mother and sister had a CNS hemangioblastoma at ages 40 and 50, respectively. His nephew presented with a CNS hemangioblastoma (age 15), a retinal angioma (age 27), and renal cell carcinoma (age 25). His daughter had a retinal angioma at age 14, and a CNS hemangioblastoma at age 24. No genetic testing information was available for family members.

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

      CaseHPOFreeText: The proband presented with a CNS hemangioblastoma at age 29. At age 46, they presented with renal cell carcinoma and a pheochromocytoma. At age 49 they presented with multiple pancreatic cysts/tumors.

      CaseNotHPOs: HP:0009711; (Retinal Capillary Hemangioma)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: Kindred #79 was published in Wang et al., 2014 (PMID: 24581539). This cohort 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.R167Q (c.500G>A)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 2216, https://www.ncbi.nlm.nih.gov/clinvar/variation/2216/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: R167Q (c.500G>A)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Chinese DiseaseEntity:VHL DiseaseEntity:hemangioblastoma DiseaseEntity:abnormalityofthepancreas DiseaseEntity:pancreaticcysts DiseaseEntity:pheochromocytoma DiseaseEntity:renalcellcarcinoma AgeOfPresentation:hemangioblastoma:29 AgeOfPresentation:abnormalityofthepancreas:49 AgeOfPresentation:pancreaticcysts:49 AgeOfPresentation:pheochromocytoma:46 AgeOfPresentation:renalcellcarcinoma:46 Mutation:Germline AssumedRefSeq:NM_000551.3 cDNAposition:500 ProteinPosition:167 AminoAcidChange:ARGtoGLN ClinVarID:2216 ClinVarID:Yes MutationType:missense_variant;transition CivicName:R167Q(c.500G>A) Familial SupplementalData PreviouslyPublished:29330336 PreviouslyPublished:24581539 inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
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    ncbi.nlm.nih.gov/pmc/articles/PMC5503545/