Molecular and clinical analysis of 126 French VHL families tested for renal involvement revealed 92 different mutations. 90 of these families had renal involvement. The p.Y175* (c.525C>G) germline variant of the VHL gene was detected in a family (ID 63). Member 2656 had unknown renal involvement. Members 2511, 4325, 2744 and 2668 presented with mild renal disease (RCC). Members 2588, 2746 and 4630 presented with moderate renal disease (RCC). Members 2060 and 2279 presented with severe renal disease (RCC). The paper states that this family is previously reported in PMID 12202531 and/or 9829912.

PatientID: None

KindredID: 51

Case: M, 41Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CohortInfo: A total of 190 patients recruited by the COMETE network over 15 years were included in the study.

CasePresentingHPOs: HP:0002666 (pheochromocytoma)

CaseHPOFreeText: The patient had one benign pheochromocytoma.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET, SDHB, SDHC, SDHD

PreviouslyPublished: N/A

SupplementalData: Patient information was extracted from Table 1 of Supplementary.

Variant: p.Y175* (c.525C>G)

CaseProblemVariantFreeText: The protein change was written as Thr175 in the Supplemental but the nucleotide change corresponds to Tyr175.

LegacyVariant: N/A

ClinVarID: 182974 https://www.ncbi.nlm.nih.gov/clinvar/variation/182974/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: stop_gained

CivicName: Y175* (c.525C>G)

MultipleGeneVariants: N/A

202 pheochromocytomas/paragangliomas, including 75 hereditary tumors, were analyzed using expression profiling, BAC array comparative genomic hybridization and somatic mutation screening. The authors describe 25 patients with germline VHL mutations and pheo/pg tumours in the Supplementary Material Table S1. Family history and other phenotypes of the patients are not described. Age reported represents age of diagnosis. A 41Y male with benign pheochromocytoma was found with a germline VHL point mutation (c.525C>G; p.Tyr175, stated in the paper incorrectly as p.Thr175).

GroupID: 32

Case: Sex, Age, Ethnicity unknown

DiseaseAssertion: VHL

FamilyInfo: Unknown. One registrant from France has this mutation of c.525C>G

CasePresentingHPOs: HP:0030393 (Endolymphatic sac tumor)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Y175* (c.525C>G)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 182974 https://www.ncbi.nlm.nih.gov/clinvar/variation/182974/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: stop_gained

CivicName: Y175* (c.525C>G)

MultipleGeneVariants: N/A

Screening of 92 unrelated patients with VHL disease revealed 61 DNA variants. Blood samples were isolated and sequenced by direct sequencing using prism-ready reaction dye primer cycle sequencing kits (Applied Biosystem Roissy CDG France) and an ABI 373A automated sequencer (AppliedBiosystem Roissy CDG France). No variants were found in 96 control cases. This stop-gain mutation, c.525C>G, was found in a VHL type 1 patient (patient no. V63). No patient information was provided and no additional family members were screened.

PatientID: 96

KindredID: None

Case: Age and Sex unknown, Chinese

DiseaseAssertion: VHL

FamilyInfo: None

CasePresentingHPOs: HP:0010797; HP:0001737; HP:0000107 (hemangioblastoma, pancreatic cysts, renal cyst)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0005584; HP:0009711; HP:0002666; HP:0030405; HP:0030393 (Renal cell carcinoma, Retinal capillary haemangioblastoma, Pheochromocytoma, Pancreatic endocrine tumour, Endolymphatic sac tumour)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Yes; See Suppl 1 (Supporting table)

Variant: p.Y175* (c.525C>G)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 182974 https://www.ncbi.nlm.nih.gov/clinvar/variation/182974/

CAID: CA020466 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.525C%3EG

gnomAD: N/A

VariantEvidence: N/A

MutationType: stop_gained

CivicName: Y175* (c.525C>G)

MultipleGeneVariants: N/A