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  1. Last 7 days
  2. 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 01 Nov 2026
      333C>G111S111R

      A study of 34 Polish families revealed germline mutations in 30 families using DNA isolated from peripheral blood luykocytes to sequence through PCR and Quantitative Southern analysis. Mutations were not detected in 4 probands fulfilling clinical criteria for von Hippel-Lindau disease (VHLD). This missense mutation was found in a VHL patient with hemangioblastomas of the central nervous system and retina (family no. 12). There was no family history of VHL, however the parents were not tested.

      ClinVarID:223187 EvidenceStatement inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
    2. ClingenBaseline 30 Oct 2026
      333C>G

      GroupID/ KindredID: 12

      Case: Age unknown, Sex unknown, Polish

      DiseaseAssertion: VHL

      FamilyInfo: This mutation was found in Family No. 12 with 1 member affected. There was no family history of VHL, however the parents were not tested (No confirmed de novo)

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

      CaseHPOFreeText: N/A

      CaseNotHPOs: HP:0005584 (renal cell carcinoma)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: N/A

      PreviouslyPublished: N/A

      SupplementalData: N/A

      Variant: p.S111R (c.333C>G)

      CaseProblemVariantFreeText: N/A

      LegacyVariant: N/A

      ClinVarID: 223187 https://www.ncbi.nlm.nih.gov/clinvar/variation/223187/

      CAID: N/A

      gnomAD: N/A

      VariantEvidence: N/A

      MutationType: missense_variant; transversion

      CivicName: S111R (c.333C>G)

      MultipleGeneVariants: N/A

      DiseaseEntity:VHL DiseaseEntity:retinalcapillaryhemangioma DiseaseEntity:hemangioblastoma Ethnicity:Polish Mutation:Germline AssumedRefSeq:NM_000551.3 ProteinPosition:111 cDNAposition:333 MutationType:missense_variant;transversion CivicName:S111R(c.333C>G) AminoAcidChange:SERtoARG ClinVarID:223187 ClinVarID:Yes ExperimentalAssay inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    jmg.bmj.com/content/39/7/e38
  3. Oct 2026
  4. 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 27 Oct 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 (S111R (c.333C>G)) was taken from the National Cancer Institute database, with an unknown number of members belonging to Family ID 4401NCI. It was reported in the paper as c.546C>G 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:223187 EvidenceStatement inferred_gene_hgnc:12687 inferred_gene_source:ClinVar VHL Hypothesis Annotation
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    pubmed.ncbi.nlm.nih.gov/8956040/
  5. 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
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    jmg.bmj.com/content/39/7/e38