PatientID: 6

KindredID: 6

Case: F, 42Y0M, Ethnicity unknown

DiseaseAssertion: VHL

FamilyInfo: Familial association - patient was selected from the group of familial VHL patients. This VHL germline mutation was detected in a close relative.

CasePresentingHPOs: HP:0001737; HP:0010797; HP:0030405 (pancreatic cysts; hemangioblastoma; pancreatic endocrine tumour)

CaseHPOFreeText: 2 single benign cysts, 6 macroscopic (and 1 microscopic) microcystic adenomas

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Val62Cysfs*5 (c.180delG)

LegacyVariant: p.V137Cfs*5 (c.393delG)

ClinVarID: 182986 https://www.ncbi.nlm.nih.gov/clinvar/variation/182986/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: V62fs (c.180delG)

MultipleGeneVariants: N/A

GroupID/ KindredID: 3563NCI

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, with an unknown number of members belonging to Family ID 3563NCI. Table 3 lists all ID and mutations associated with individuals possessing renal carcinoma, without phechromocytoma.

GroupPresentingHPOs: HP:0005548 (renal cell carcinoma)

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

GroupNotHPOs: HP:0002666 (pheochromocytoma)

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: 7728151; 9829911

SupplementalData: N/A

Variant: p.V62Cfs*5 (c.180delG)

LegacyVariant: (c.393delG)

CaseProblemVariantFreeText: N/A

ClinVarID: 182986 https://www.ncbi.nlm.nih.gov/clinvar/variation/182986/

CAID: N/A

gnomAD: N/A

VariantEvidence: This paper declares this variant is predicted to compromise the Elongin-binding site by truncating the protein.

MutationType: minus_1_frameshift_variant

CivicName: V62fs (c.180delG)

MultipleGeneVariants: N/A

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 (V62fs (c.180delG)) was taken from the National Cancer Institute database, with an unknown number of members belonging to Family ID 3563NCI. It was reported in the paper as c.393delG due to a difference in transcript reference. As reported in Table 3, this mutation is found in VHL family without pheochromocytoma, and with renal cell carcinoma. Later publications reference this cohort as being reported in PMIDs: 7728151 and 9829911.