16 Matching Annotations
  1. Last 7 days
  2. 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
    1
    1. ClingenBaseline 05 Nov 2026
      Germline mutations were identified in 300/469 (63%) of the families tested; 137 distinct intragenic germline mutations were detected.

      Germline mutational data on VHL was gathered from various countries to assess variation in germline mutations that produce disease within different populations. Families were grouped according to three possible outcomes of disease: renal cell carcinoma without pheochromocytoma, renal cell carcinoma with pheochromocytoma, or pheochromocytoma alone. SSCP and denaturing gradient gel electrophoresis identified mutations in 300/469 (63%) of families affected with VHL. This germline familial VHL mutation (C162Y (c.485G>A)) was taken from the Department of Uroglogy, Yokohama database, with an unknown number of members belonging to Family ID 11YO. It was reported in the paper as c.698G>A due to a difference in transcript reference. As reported in Table 3, this mutation is found in VHL families without pheochromocytoma, and with renal cell carcinoma.

      ClinVarID:223225 EvidenceStatement inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    Visit annotations in context

    Tags

    Annotators

    URL

    pubmed.ncbi.nlm.nih.gov/8956040/
  3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Genotype-phenotype correlation in von Hippel-Lindau families with renal lesions
    1
    1. ClingenBaseline 05 Nov 2026

      GroupID: 17

      DiseaseAssertion: VHL

      GroupSize: 5

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: French

      GroupAgeRange: N/A

      GroupInfo: 5 members of this family presented with the c.485G>A germline variant of the VHL gene. Member 753 presented with moderate renal disease (RCC), member 11338 had unknown renal involvement, member 696 presented with severe renal disease (RCC) and members 2368 and 699 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; 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]). Severe renal disease (any solid lesion before 25 years of age, five or more solid lesions within one or two kidneys, or metastasis of renal cell carcinoma).

      GroupNotHPOs: N/A

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: Phenotype and genotype information can be found in Supplementary Table S1.

      Variant: p.C162Y (c.485G>A)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 223225, https://www.ncbi.nlm.nih.gov/clinvar/variation/223225/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: C162Y (c.485G>A)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:French DiseaseEntity:VHL DiseaseEntity:renalneoplasm DiseaseEntity:renalcellcarcinoma Mutation:Germline RefSeq:NM_000551.3 cDNAposition:485 ProteinPosition:162 AminoAcidChange:CYStoTYR ClinVarID:223225 ClinVarID:Yes MutationType:missense_variant;transition CivicName:C162Y(c.485G>A) Familial FamilyCohort SupplementalData inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    Visit annotations in context

    Tags

    Annotators

    URL

    pubmed.ncbi.nlm.nih.gov/15300849/
  4. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    The Endothelial Landscape and Its Role in Von Hippel-Lindau Disease
    1
    1. ClingenBaseline 04 Nov 2026
      3.4. Tubulogenesis and Angiogenesis Assays of VHL versus Control BOECsUpon isolation and expansion of BOECs, it was visually clear that BOECs derived from VHL patients appeared morphologically different from healthy controls (Figure 5A). While controls appear as elongated and in closer contact, VHL BOECs are less elongated, rather rounded, and sparsely distributed. Angiogenesis can be measured in vitro by two functional assays for ECs: tubulogenesis and wound healing. VHL patient-derived BOECs showed differences compared to the control group. In the tubulogenesis assay, VHL cells displayed a significantly reduced number of closed tubules (Figure 5B). On the other hand, they were slower on average when migrating to cover the discontinuity inflicted in the confluent monolayers or wound (Figure 5C).Open in a separate windowFigure 5Morphological and functional differences between ECs derived from either healthy subjects or VHL patients. (A) Control and VHL ECs photographed under the microscope once confluence levels were reached. (B) Tubulogenesis assay performed on ECs from control vs. VHL groups, photographed 3 h after cell seeding on Matrigel-matrix-coated wells. (C) Wound healing assay performed on ECs from control vs. VHL groups, photographed 6.5 h after wound infliction on confluent wells. Error bars denote ± SEM. Student’s t-test: ** p < 0.01; and *** p < 0.001.3.5. VEGF Signaling PathwayThe VEGF signaling pathway appeared upregulated in VHL BOECs, according to the GSEA analysis (Figure 6A). Western blotting was used to check the phosphorylation of regulatory kinases belonging to the VEGFA-VEGFR2 pathway (AKT and ERK1/2) (Figure 6B).Open in a separate windowFigure 6(A) VEGF signaling pathway appeared upregulated, according to the GSEA analysis. (B) ERK1/2 and AKT phosphorylation assessment by Western Blot. Densitometric quantification of phosphorylated/total protein ratios are shown for control subject (n = 2) or VHL patients (n = 2). Error bars denote ± SEM. Student’s t-test: * p < 0.05 and *** p < 0.001.3.6. VHL ECs Have Higher Expression of ROSFigure 7A shows a table collecting genes involved in the ROS metabolism, which are downregulated in VHL ECs. Accordingly, a measure of ROS was made from in vitro cultures of control and VHL-derived ECs. In Figure 7B, a representative histogram of the results is depicted. As expected, and supporting the RNAseq results, we found that VHL ECs have on average almost double the amount of ROS than their non-VHL counterpart.Open in a separate windowFigure 7(A) ROS metabolism modulation in RNAseq analysis in VHL ECs. (B) ROS levels in control and VHL cells, showing a significant increase in VHL samples. Error bars denote ± SEM. Student’s t-test: ** p < 0.01.3.7. VHL Gene Expression in VHL Patients’ ECsNo differences in VHL gene expression were found between the patients and the control group, despite the heterozygosis of the patients in the VHL gene. This result could be explained by the type of mutation these patients present: four out of five present missense mutations (Table 1, Figure 3). Only in sample 4, where the mutation affects the splicing site of the DNA, the RNA levels show a lower tendency, although not significant (Table S1). In order to visualize the translational effect of the patients’ mutations, we mapped them on the 3D structure of pVHL, highlighting the changes in amino acids (Figure 8A,B). The altered amino acids fall within areas of close contact between the different subunits, which could affect its proteolytic activity and the assembly of a functional proteasomal complex. Proper folding of the protein, an altered interaction with the substrates, or assembly of the E3 ligase complex, which most likely lead to its loss of function. Further computational analysis should be performed to elucidate the definite cause of how those mutations impair protein function.Open in a separate windowFigure 8(A) 3D complex structure (PDB ID: 4AJY) of the von Hippel–Lindau protein (yellow), Elongin B (green), and Elongin C (purple), bound to Hif1- alpha peptide (depicted in dark blue), highlighting the heterodimerization interface of this complex in a gray box and the position of the R64P mutation. (B) Inset of the VHL-ELOb/c interface with their respective involved amino acids are represented as sticks, while the relevant mutation positions are represented with spheres and labelled in bold. (C) Confocal staining of sample V1 (p.R167Q) shows the distribution of pVHL in the cell cytoplasm, distributed in the perinuclear region in VHL cells and throughout the cell in control ones.A misfolding of the protein could explain the differential distribution of pVHL in sample V1 (p.R167Q). Confocal staining of ECs shows that pVHL accumulates in the perinuclear region. This result suggests a likely aggregation of pVHL in endoplasmic reticulum cysts. Conversely, control ECs show a more heterogeneous distribution of pVHL throughout the cytoplasm (Figure 8C). We believe that these differences in cellular pVHL distribution are caused by the mutations in pVHL present in this patient.
      ExperimentalAssay ClinVarID:2216 ClinVarID:2226 ClinVarID:223225 ClinVarID:1298905 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    Visit annotations in context

    Tags

    Annotators

    URL

    ncbi.nlm.nih.gov/pmc/articles/PMC8465092/
  5. 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 02 Nov 2026
      1 France c.485G>A p.Cys162Tyr

      Patients with ELSTs were identified and included in the International Endolymphatic Sac Tumor Registry. The registry contained 93 patients as of July 2014, and of those, 25 were sporadic, and 68 associated with VHL. Patients with ELSTs and clinically confirmed diagnoses of VHL were included in this study. Statistics of this VHL subgroup are as follows: mean age 30, 62% female, 91% symptomatic, 54% with retinal angioma, 72% with CNS hemangioblastoma, 46% with renal cell carcinoma, 19% with pheochromocytoma, and 12% with pancreatic neuroendocrine tumour. In the data from this study, only endolymphatic sac tumours can be confirmed as a phenotype for this mutation (c.485G>A), which was found in 1 individual from France.

      EvidenceStatement ClinVarID:223225 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    Visit annotations in context

    Tags

    Annotators

    URL

    onlinelibrary.wiley.com/doi/full/10.1002/hed.24067
  6. 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

      A retrospective cohort study included all the VHL patients diagnosed at Peking University First Hospital (Beijing, China) prior to June 1 2016. A total of 291 patients from 115 different families were included for analysis. One female patient, patient 172, from kindred #68, was found with this germline mutation p.C162Y (c.485G>A). She was diagnosed with a CNS hemangioblastoma, renal cell carcinoma, and multiple pancreatic cysts/tumors at 43Y. This individual was also likely published in a later paper by Wang et al., 2018 (PMID: 29330336). No family information was described.

      EvidenceStatement ClinVarID:223225 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    Visit annotations in context

    Tags

    Annotators

    URL

    ncbi.nlm.nih.gov/pmc/articles/PMC5503545/
  7. link.springer.com link.springer.com
    Germline mutations in the von Hippel–Lindau disease (VHL) gene in mainland Chinese families
    1
    1. ClingenBaseline 31 Oct 2026
      Cys162Tyr

      27 index patients suspected of having VHL disease from unrelated Chinese families and their relatives were studied. The nucleotide were numbered according to the sequence numbering by Latif et al, 1993 and this was converted to NM_000551.3. The paper did not differentiate between a pancreatic cysts and tumor and presented these together as a 'pancreatic lesion'. The paper summariezed the phenotypes of the families together. Family 18 was found with p.Cys162Tyr mutation in the VHL gene: 2/2 members had CNS hemangioblastoma, 1/2 had RCC and 1/2 had a pancreatic lesion. ACMG PP4

      ClinVarID:223225 EvidenceStatement inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    Visit annotations in context

    Tags

    Annotators

    URL

    link.springer.com/article/10.1007/s00432-008-0399-x
  8. 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 31 Oct 2026

      A previous study of 26 Japanese, VHL families was extended to 41 additional families. Germline mutations were detected in 55 of 77 Japanese families using SSCP, direct sequencing, and Southern Blot analysis of peripheral blood samples. The C162Y (c.485G>A) germline missense mutation of the VHL gene was found in a VHL patient with retinal angiomas, pancreatic cysts or tumor (unspecified), renal cell carcinoma, and pheochromocytoma (family ID 104). The variant was also found in a family of 4 individuals all presenting with CNS hemangioblastoma (family ID 11). This family was previously reported in PMID 8634692.

      EvidenceStatement ClinVarID:223225 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    Visit annotations in context

    Tags

    Annotators

    URL

    pubmed.ncbi.nlm.nih.gov/10761708/
  9. Oct 2026
  10. link.springer.com link.springer.com
    Germline mutations in the von Hippel–Lindau disease (VHL) gene in mainland Chinese families
    1
    1. ClingenBaseline 28 Oct 2026
      Cys162Tyr

      GroupID/ KindredID: 18

      DiseaseAssertion: assumed VHL

      GroupSize: 2

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: Chinese

      GroupAgeRange: N/A

      GroupInfo: With a family history, 2 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: both (2) members had CNS hemangioblastomas, 1 had RCC, 1 had a pancreatic abnormality

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

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

      GroupPreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.C162Y (c.485G>A)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: p.C162Y (c.698G>A)

      ClinVarID: 223225 https://www.ncbi.nlm.nih.gov/clinvar/variation/223225/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transition

      CivicName: C162Y (c.485G>A)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline DiseaseEntity:hemangioblastoma DiseaseEntity:abnormalityofthepancreas DiseaseEntity:renalcellcarcinoma RefSeq:AF010238.1 CivicName:C162Y(c.485G>A) cDNAposition:485 ProteinPosition:162 AminoAcidChange:CYStoTYR MutationType:missense_variant;transition ClinVarID:223225 ClinVarID:Yes Familial FamilyCohort Ethnicity:Chinese inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    Visit annotations in context

    Tags

    Annotators

    URL

    link.springer.com/article/10.1007/s00432-008-0399-x
  11. onlinelibrary.wiley.com onlinelibrary.wiley.com
    Genetic characterization and structural analysis of VHL Spanish families to define genotype–phenotype correlations
    3
    1. ClingenBaseline 28 Oct 2026

      GroupID/ KindredID: F61

      Case: Sex unknown, 15Y0M, Spanish

      DiseaseAssertion: assumed VHL

      FamilyInfo: familial antecedents found of clear cell RCC

      CasePresentingHPOs: HP:0009711; HP:0002666; HP:0000107 (retinal capillary hemangioma, pheochromocytoma, renal cysts)

      CaseHPOFreeText: Unilateral pheo. Age of onset is 15Y0M.

      CaseNotHPOs: HP:0006880; HP:0006770; HP:0001737 (cerebellar hemangioblastoma, clear cell renal cell carcinoma, pancreatic cysts)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.C162Y (c.485G>A)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 223225 https://www.ncbi.nlm.nih.gov/clinvar/variation/223225/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transition

      CivicName: C162Y (c.485G>A)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline Ethnicity:Spanish Familial ExperimentalAssay MutationType:missense_variant;transition cDNAposition:485 CivicName:C162Y(c.485G>A) ProteinPosition:162 AminoAcidChange:CYStoTYR ClinVarID:223225 ClinVarID:Yes DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:renalcyst DiseaseEntity:pheochromocytoma inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 27 Oct 2026

      Thirty-five unrelated patients suspected of having von Hippel-Lindau disease were analyzed and 32 VHL gene variants were found in 35 patients using PCR and SSCP by peripheral blood leukocytes. An association of clear cell renal carcinoma development with a relatively high loss of structural stability in VHL protein missense mutations was discovered. This missense mutation (p.C162Y) was found in a patient, whose age of onset was 15 years old, with retinal hemangioblastomas, unilateral pheochromocytoma, and renal cysts (patient no. F61). Patient has family history of clear cell renal carcinoma.

      ClinVarID:223225 EvidenceStatement inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    Visit annotations in context

    Tags

    Annotators

    URL

    onlinelibrary.wiley.com/doi/abs/10.1002/humu.10309
  12. academic.oup.com academic.oup.com
    VHL mutation analysis in patients with isolated central nervous system haemangioblastoma
    1
    1. ClingenBaseline 27 Oct 2026
      B6 CHB 22 c.698G → A, C162Y No 2 y 7 m Nil No testing 

      Patient ID: B6

      KindredID: 6

      Case: F, 22Y0M, Ethnicity Unknown

      DiseaseAssertion: cerebellar hemangioblastoma

      FamilyInfo: No testing in family history

      CasePresentingHPOs: HP:0006880 (cerebellar hemangioblastoma)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: no other clinical features were found after the cerebellar hemangioblastoma during 2 years and 7 month follow-up

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.C162Y (c.485G>A)

      LegacyVariant: p.C162Y (c.698G>A)

      ClinVarID: 223225 (https://www.ncbi.nlm.nih.gov/clinvar/variation/223225/)

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: C162Y(c.485G>A)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant DiseaseEntity:cerebellarhemangioblastoma Mutation:Germline cDNAposition:485 ProteinPosition:162 AminoAcidChange:CYStoTYR ClinVarID:223225 MutationType:missense_variant;transition CivicName:C162Y(c.485G>A) RefSeq:AF010238.1 AgeOfPresentation:cerebellarhemangioblastoma:22 ClinVarID:Yes NoFamilyInfo inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    Visit annotations in context

    Tags

    Annotators

    URL

    academic.oup.com/brain/article/130/3/836/278946
  13. 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 27 Oct 2026

      GroupID: 11

      DiseaseAssertion: VHL

      GroupSize: 4

      GroupNumberMales: N/A

      GroupNumberFemales: N/A

      GroupEthnicity: Japanese

      GroupAgeRange: N/A

      GroupInfo: 4 individuals from a single family (ID 11).

      GroupPresentingHPOs: HP:0010797 (Hemangioblastoma)

      GroupHPOFreeText: CNS hemangioblastoma (4/4).

      GroupNotHPOs: HP:0001732; HP:0005584; HP:0009711 (Abnormality of the pancreas, Renal cell carcinoma, Retinal capillary hemangioma)

      GroupNotHPOFreeText: N/A

      GroupPreviousTesting: N/A

      PreviouslyPublished: 8634692

      SupplementalData: N/A

      Variant: p.C162Y (c.485G>A)

      LegacyVariant: c.698G>A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 223225, https://www.ncbi.nlm.nih.gov/clinvar/variation/223225/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: C162Y (c.485G>A)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Ethnicity:Japanese DiseaseEntity:VHL DiseaseEntity:hemangioblastoma Mutation:Germline RefSeq:AF010238.1 cDNAposition:485 ProteinPosition:162 AminoAcidChange:CYStoTYR ClinVarID:Yes ClinVarID:223225 MutationType:missense_variant;transition CivicName:C162Y(c.485G>A) Familial FamilyCohort inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    Visit annotations in context

    Tags

    Annotators

    URL

    pubmed.ncbi.nlm.nih.gov/10761708/
  14. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Genotype-phenotype correlation in von Hippel-Lindau families with renal lesions
    1
    1. ClingenBaseline 27 Oct 2026

      Molecular and clinical analysis of 126 French VHL families tested for renal involvement revealed 92 different mutations. 90 of these families had renal involvement. The p.C162Y (c.485G>A) germline variant of the VHL gene was detected in a family (ID 17). Member 753 presented with moderate renal disease (RCC), member 11338 had unknown renal involvement, member 696 presented with severe renal disease (RCC) and members 2368 and 699 presented with mild renal disease.

      EvidenceStatement ClinVarID:223225 inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    Visit annotations in context

    Tags

    Annotators

    URL

    pubmed.ncbi.nlm.nih.gov/15300849/
  15. 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
    1
    1. ClingenBaseline 26 Oct 2026
      The VHL gene product (pVHL) has two macromolecular sites, α and β domains, which can bind different proteins. pVHL bound to elongin B, C/cullin/Rbx1 acts as an E3 ubiquitin ligase and targets proteins for degradation.22 Similarly, hypoxia inducible proteins are regulated by complex pVHL/elongin B and C that requires direct binding of hypoxia inducible factor (HIF) to the β domain and targets HIF for ubiquitination catalysed by the α domain.23 The VHL protein also plays a role in extracellular matrix formation and is necessary for cell cycle exit.24,25 Germline VHL mutations cause different protein defects that result in the clinical heterogeneity of VHL disease. VHL type 1 disease (without phaeochromocytoma) is associated with mutations predicted to cause complete unravelling of protein structure (missense mutations mapping to VHL protein hydrophobic core, protein truncating mutations, and partial gene deletions). VHL type 2 (with phaeochromocytoma) is caused by missense mutations which map to protein binding sites of pVHL and are predicted to cause local protein defects.22 Specific phaeochromocytoma associated missense mutations confer different risks of HAB and RCC, being responsible for the occurrence of subcategories VHL type 2A (VHL without RCC), 2B (VHL with RCC), and 2C (phaeochromocytoma only).15 Phenotypic expression of VHL disease is also influenced by genetic modifiers.26
      ExperimentalAssay ClinVarID:182975 CAID:CA432536422 CAID:CA357012 ClinVarID:93326 CAID:CA658683075 ClinVarID:2216 ClinVarID:2217 ClinVarID:223225 CAID:CA645525053 CAID:CA432421902 ClinVarID:223187 ClinVarID:223169 inferred_gene_hgnc:12687 inferred_gene_source:CAID VHL Hypothesis Annotation
    Visit annotations in context

    Tags

    Annotators

    URL

    jmg.bmj.com/content/39/7/e38
  16. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    The Endothelial Landscape and Its Role in Von Hippel-Lindau Disease
    1
    1. ClingenBaseline 23 Oct 2026
      V#2exon 3c.485G > Ap.C162YCNS-HB

      PatientID: 2

      KindredID: 2

      Case: Sex Unknown, Age Unknown, Ethnicity Unknown

      DiseaseAssertion: VHL

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0010797 (hemangioblastoma)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: Yes

      Variant: p.C162Y (c.485G>A)

      LegacyVariant: N/A

      CaseProblemVariantFreeText: N/A

      ClinVarID: 223225, https://www.ncbi.nlm.nih.gov/clinvar/variation/223225/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant;transition

      CivicName: C162Y (c.485G>A)

      MultipleGeneVariants: N/A

      InheritancePattern:AutosomalDominant Mutation:Germline AssumedRefSeq:NM_000551.3 SupplementalData DiseaseEntity:VHL DiseaseEntity:hemangioblastoma NoFamilyInfo ProteinPosition:162 cDNAposition:485 AminoAcidChange:CYStoTYR ClinVarID:223225 ClinVarID:Yes MutationType:missense_variant;transition CivicName:C162Y(c.485G>A) ExperimentalAssay inferred_gene_hgnc:12687 inferred_gene_source:RefSeq VHL Hypothesis Annotation
    Visit annotations in context

    Tags

    Annotators

    URL

    ncbi.nlm.nih.gov/pmc/articles/PMC8465092/