56 male patients age 12 to 76 years, from 40 families with VHL were examined as part of a larger screening program for VHL. VHL mutations were identified in 16 families. Individual patient phenotype-genotype data was not available, but the mutations found and whether the corresponding patient had epididymal cystadenoma (EC) was reported. A p.Asn78His (c.232A>C) VHL mutation was found in a VHL patient with EC. This mutation was referred to in the paper as c.445A>C due to a difference in transcript sequence.

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 (N78H (c.232A>C)) was taken from multiple databases including: the National Cancer Institute database, the Department of Uroglogy, Yokohama database, and the Cambridge, Department of Pathology database, with an unknown number of members belonging to Family IDs 4389NCI, 1YO, 34CA. It was reported in the paper as c.445A>C 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.

GroupID/ KindredID: 4389NCI, 1YO, 34CA

DiseaseAssertion: VHL

GroupSize: N/A

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: This germline familial VHL mutation was taken from the National Cancer Institute database, the Department of Uroglogy, Yokohama database, and the Cambridge, Department of Pathology database, with an unknown number of members belonging to Family ID 4389NCI, 1YO, 34CA. Table 3 lists all ID and mutations associated with individuals possessing renal carcinoma, without pheochromocytoma.

GroupPresentingHPOs: HP:0005548 (renal cell carcinoma)

GroupHPOFreeText: Described as a VHL family with RCC, without pheochromocytoma. Other phenotypes are likely, however not detailed in this publication

GroupNotHPOs: HP:0002666 (pheochromocytoma)

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.N78H (c.232A>C)

LegacyVariant: p.N78H (c.445A>C)

CaseProblemVariantFreeText: N/A

ClinVarID: 625225 https://www.ncbi.nlm.nih.gov/clinvar/variation/625225/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: N78H (c.232A>C)

MultipleGeneVariants: N/A