5 Matching Annotations
  1. Last 7 days
  2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Pathogenicity of VHL variants in families with non-syndromic von Hippel-Lindau phenotypes: An integrated evaluation of germline and somatic genomic results
    1
    1. ClingenBaseline 03 Nov 2026
      p.Tyr98His

      PatientID: 3

      KindredID: C

      Case: F, 40Y0M, Ethnicity Unknown

      DiseaseAssertion: Hemangioblastoma

      FamilyInfo: Positive: The patient’s sister, one of two brothers, and mother each had the same germline mutation, although without any manifestations. As such, her family history was negative for kidney cancer, hemangioblastoma, or other features of VHL. See Fig. 3.

      CasePresentingHPOs: HP:0006880 (cerebellar hemangioblastoma)

      CaseHPOFreeText: In 2013, at 32Y, patient presented with a hemangioblastoma in her cerebellar region.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: No other VHL- related tumors are present in this patient.

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: Yes

      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: Immunohistochemistry was positive for Inhibin, and negative for RCC, GFAP, and OLIG2.

      MutationType: missense_variant; transition

      CivicName: P81S (c.241C>T)

      MultipleGeneVariants: Somatic, VHL, c.188_188T>TG (p.Leu63fs*4)

      InheritancePattern:AutosomalDominant Mutation:Germline AssumedRefSeq:NM_000551.3 DiseaseEntity:cerebellarhemangioblastoma AgeOfPresentation:cerebellarhemangioblastoma:32 CivicName:P81S(c.241C>T) cDNAposition:241 AminoAcidChange:PROtoSER MutationType:missense_variant;transition ProteinPosition:81 ClinVarID:2233 ClinVarID:Yes SupplementalData Familial FamilyPedigree MultipleVHLVariants inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    Visit annotations in context

    Tags

    Annotators

    URL

    pubmed.ncbi.nlm.nih.gov/34628056/
  3. Oct 2026
  4. academic.oup.com academic.oup.com
    Hemangioblastomas of Central Nervous System: Molecular Genetic Analysis and Clinical Management
    1
    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
    Visit annotations in context

    Tags

    Annotators

    URL

    academic.oup.com/neurosurgery/article-abstract/56/6/1215/2744028
  5. www-sciencedirect-com.uhn.idm.oclc.org www-sciencedirect-com.uhn.idm.oclc.org
    A deletion mutation of the VHL gene associated with a patient with sporadic von Hippel-Lindau disease
    1
    1. ClingenBaseline 26 Oct 2026
      2. Materials and methods2.1. PatientThe 32-year-old male patient was admitted to Xiangya Hospital in 2006 and presented with progressive back and neck pain, and numbness and weakness of both legs which had continued for 1 month followed by fecal and urinary retention for 5 days. The MRI (1.5 Tesla) of the brain and entire spinal cord showed multiple lesions in the cerebellum, brain stem, and spinal cord, which were obviously enhanced and highly suggestive of hemangioblastomas (Fig. 1a–e). Subsequent evaluation, by MRI, of the abdomen revealed a solid kidney tumor (Fig. 1f). He underwent surgical resection for hemangioblastomas of T10 and T12 of the spinal cord, which appeared bright red at surgery. The pathological examination of the tissues showed many small blood vessels, most of which were a capillary plexus. Vascular endothelial cells were flat and distributed within a large number of stromal cells. Some of the vascular endothelial cells formed solid masses and cords. Between the capillary plexus, various forms of stromal cells were found, including nest-like or sheet arrangements with hyperchromatic nuclei, rich cytoplasm, rich lipid vacuoles and rare or no mitoses. Some foam cells and adipose-like cells were also found. Immunohistochemistry of the biopsied tissues from the lesions in the spinal cord were negative on immunostaining (–) for glial fibrillary acidic protein (GFAP), CD68, cytokinin (CK)-pan and epithelial membrane antigen (EMA), but stained positive (+) for factor 8 related antigen (F8RAg). Vascular endothelial cells were F8RAg(+) but stromal cells were F8RAg(–). Vascular endothelial cells and stromal cells were all immunonegative for GFAP, EMA, CK-pan, and CD68 (Fig. 1g, h). The patients’ symptoms resolved after surgery. At 5-year follow-up his condition did not recur or deteriorate, but active surveillance was continued.12Download : Download high-res image (1MB)Download : Download full-size imageFig. 1. Main clinical manifestations of von Hippel-Lindau (VHL) disease. (a) Sagittal T1-weighted MRI of the thoracic spinal cord showing two brightly enhancing nodular lesions with clear boundaries at T10 and T12 (arrows). (b) Sagittal T1-weighted MRI of the cervical spinal cord showing two brightly enhancing nodular lesions with clear boundaries at C5 and C6 (arrows). (c) Sagittal T1-weighted MRI of the cervical spinal cord showing a brightly enhancing nodular lesion with a clear boundary at C2 (arrow). (d) Sagittal T1-weighted MRI of the cranial–cervical region showing three brightly enhancing round lesions with clear boundaries at the posterior of the medulla oblongata, superior spinal cord and basilar part of the pons (arrows). (e) Axial T1-weighted MRI of the brain showing two brightly enhancing nodular lesions with clear boundaries at the posterior of the medulla oblongata and the right cerebellar hemisphere (arrows). (f) Sagittal T1-weighted MRI of the kidney showing the small (1.2 cm × 0.6 cm) enhancing nodular lesion (arrow). (g) Histopathological examination of the lesions at T10 and T12 in the spinal cord of the patient with VHL (hematoxylin and eosin stain, ×400). (h) Immunohistochemistry of the biopsied tissue from the lesions at T10 and T12 in the spinal cord of the patient with VHL (factor 8 related antigen stain, ×400).After genetic counseling, all family members of the patient (his parents, sister, son, sister’s son, brother, and brother’s son) were recruited into this study. His 66-year-old father and 63-year-old mother were both in good health without clinical symptoms of VHL. They did not undergo a whole-body examination, but all other family members underwent clinical examination, including ophthalmoscopy, MRI of the CNS, and ultrasonography of the abdomen, to exclude the disease. Informed consent was obtained from all individuals before their participation in the study.

      PatientID: 1

      KindredID: 1

      Case: M, 39Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: No family history. All 7 of his other family members (his parents, sister, son, sister’s son, brother, and brother’s son) were sequenced and no mutation were found. Additionally, all were healthy members. Suggestive of de novo due to no abnormal changes in the VHL gene of either parent.

      CasePresentingHPOs: HP:0010797; HP:0009713; HP:0006880; HP:0009726 (hemangioblastoma, spinal hemangioblastoma, cerebellar hemangioblastoma, renal neoplasm)

      CaseHPOFreeText: At 32Y this patient presented with progressive back and neck pain and numbness. Patient developed multiple CNS hemangioblastomas (multiple lesions in the cerebellum, brain stem, and spinal cord). Subsequent evaluation of the abdomen revealed a solid kidney tumor (visceral tumor).

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.F76del (c.227_229delTCT)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: N/A

      CAID: CA357012 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.227_229delTCT

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: inframe_deletion

      CivicName: F76del (c.227_229delTCT)

      MultipleGeneVariants: N/A

      deNovoConfirmed InheritancePattern:DeNovoAssertion DiseaseEntity:VHL DiseaseEntity:hemangioblastoma DiseaseEntity:cerebellarhemangioblastoma DiseaseEntity:spinalhemangioblastoma DiseaseEntity:renalneoplasm AgeOfPresentation:hemangioblastoma:32 AgeOfPresentation:spinalhemangioblastoma:32 AgeOfPresentation:renalneoplasm:32 AgeOfPresentation:cerebellarhemangioblastoma:32 Mutation:Germline AssumedRefSeq:NM_000551.3 CivicName:F76del(c.227_229delTCT) cDNAposition:227 ProteinPosition:76 MutationType:inframe_deletion CAID:CA357012 ClinVarID:N/A inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
    Visit annotations in context

    Tags

    Annotators

    URL

    www-sciencedirect-com.uhn.idm.oclc.org/science/article/pii/S096758681200567X
  6. 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
    Visit annotations in context

    Tags

    Annotators

    URL

    academic.oup.com/jnen/article-abstract/73/1/50/2917595
  7. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Head and Neck Paragangliomas in Von Hippel-Lindau Disease and Multiple Endocrine Neoplasia Type 2
    1
    1. ClingenBaseline 22 Oct 2026
      Case 11In 1978, an 8-yr-old girl without familial history of VHL was operated for a right pheochromocytoma and at age 13 for a contralateral pheochromocytoma. At age 15, a 4-cm mass at the neck was diagnosed by selective arteriography as a carotid paraganglioma that was removed and histologically confirmed. The patient was then operated twice for cerebellar hemangioblastoma at age 22, leading to the diagnosis of VHL disease. At age 27, the patient was operated again for a retrocaval pheochromocytoma and for islet cell tumors. The patient was also repeatedly treated for bilateral retinal hemangioblastomas leading to blindness at age 32. At age 36, again a pheochromocytoma was removed. Molecular genetic analysis identified the p.Thr157Ile VHL germline mutation. So far, there are no affected relatives.

      PatientID: 11

      KindredID: 11

      Case: F, 36Y0M, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: There was said to be, at the time, no affected relatives

      CohortInfo: An international consortium registered patients with head and neck paragangliomas with VHL or RET gene mutations.

      CasePresentingHPOs: HP:0006748; HP:0002668; HP:0006476; HP:0006880; HP:0009711; HP:0000618; HP:0010797 (adrenal pheochorocytoma, paraganglioma, abnormality of the pancreatic islet cells, cerebellar hemangioblastoma, retinal capillary hemangioblastoma, blindness, hemangioblastoma)

      CaseHPOFreeText: At 8Y, (in 1978), she was operated for a right pheochromocytoma; at age 13 for a contralateral pheochromocytoma; at age 15, for a 4-cm mass at the neck was diagnosed by selective arteriography as a carotid paraganglioma. The patient was then operated twice for cerebellar hemangioblastoma at age 22, leading to the diagnosis of VHL disease. At age 27, the patient was operated again for a retrocaval pheochromocytoma and for islet cell tumors. The patient was also repeatedly treated for bilateral retinal hemangioblastomas leading to blindness at age 32. At age 36, again a pheochromocytoma was removed

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: RET

      PreviouslyPublished: N/A

      SupplementalData: N/A

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

      LegacyVariant: p.T157I

      CaseProblemVariantFreeText: The publication only provides the p., the mutation was able to be deduced to p.T157I (c.470C>T)

      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 Familial DiseaseEntity:VHL DiseaseEntity:adrenalpheochromocytoma DiseaseEntity:paraganglioma DiseaseEntity:abnormalityofthepancreaticisletcells DiseaseEntity:cerebellarhemangioblastoma DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:blindness DiseaseEntity:hemangioblastoma AgeOfPresentation:pheochromocytoma:8 AgeOfPresentation:paraganglioma:15 AgeOfPresentation:cerebellarhemangioblastoma:22 AgeOfPresentation:abnormalityofthepancreaticisletcells:27 AgeOfPresentation:retinalcapillaryhemangioma:32 PreviousTesting:RET CivicName:T157I(c.470C>T) cDNAposition:470 ProteinPosition:157 AminoAcidChange:THRtoILE MutationType:missense_variant;transition ClinVarID:223223 ClinVarID:Yes RefSeq:NM_000551.2 inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    Visit annotations in context

    Tags

    Annotators

    URL

    ncbi.nlm.nih.gov/pmc/articles/PMC2690424/