In a study of 114 unrelated VHL families, 85 germline mutations were found. VHL mutations were detected in affected family members, but not in unaffected family members or 96 normal individuals. This frameshift mutation was found in 4 family members with VHL type 1 phenotype (Family ID 3616), using PCR and SSCP sequencing. The mutation of c.462delA was referred to in the paper by c.675delA due to a difference in transcript sequence. Two of 4 members carried retinal hemangioblastomas and 2 with renal cell carcinoma. Supporting evidence of pathogenicity because of the introduction of an early stop codon in a gene where loss of function is an established mechanism of disease (ACMG code: PVS1).

GroupID: 3616

DiseaseAssertion: assumed VHL

GroupSize: 4

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

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

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

GroupHPOFreeText: 2/4 members had retinal angiomas (hemangiomas), and 2/4 had RCC

GroupNotHPOs: HP:0010797; HP:0002666 (hemangioblastoma, pheochromocytoma)

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.V155Cfs*4 (c.462delA)

CaseProblemVariantFreeText: N/A

LegacyVariant: p.225fs (c.675delA)

ClinVarID: 625251 https://www.ncbi.nlm.nih.gov/clinvar/variation/625251/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: V155fs (c.462delA)

MultipleGeneVariants: N/A