This study reports 1,548 germline and somatic mutations from 945 VHL families, including 30 previously unpublished kindreds from The Netherlands (six novel mutations). This mutation (c.430G>T) was detected by direct sequencing and MLPA. This nonsense mutation was found as sporadic germline in a VHL case with bilateral renal cell carcinoma and hemangioblastoma (case no. 442). This was suggested to be de novo but it could not be confirmed. There is very strong evidence of pathogenicity in the form of a nonsense variant in a gene where loss-of-function is known mechanism of disease (ACMG code: PSV1).

PatientID: N/A

KindredID: 442

Case: Age unknown, Sex unknown, Ethnicity unknown

DiseaseAssertion: assumed VHL

FamilyInfo: Paper states: Germline, de novo (no clear confirmation)

CasePresentingHPOs: HP:0005584; HP:0010797 (renal cell carcinoma, hemangioblastoma)

CaseHPOFreeText: Bilateral RCC and a hemangioblastoma

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Yes (Specifically Supp. Table S2)

Variant: p.G144* (c.430G>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223208 https://www.ncbi.nlm.nih.gov/clinvar/variation/223208/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: stop_gained

CivicName: G144* (c.430G>T)

MultipleGeneVariants: N/A