PatientID: None

KindredID: 3509

Case: Sex, Age, Ethnicity Unknown

DiseaseAssertion: assumed VHL

FamilyInfo: Familial VHL stated; although only 1 family member recorded.

CasePresentingHPOs: HP:0010797; HP:0009711; HP:0005584 (hemangioblastoma, retinal capillary hemangioma, renal cell carcinoma)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0002666 (Pheochromocytoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.C162R (c.484T>C)

CaseProblemVariantFreeText: N/A

LegacyVariant: p.C233R (c.697T>C)

ClinVarID: 496067 https://www.ncbi.nlm.nih.gov/clinvar/variation/496067/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: C162R (c.484T>C)

MultipleGeneVariants: N/A

Of 16 patients presenting with clinical VHL features that underwent genetic testing, one presented with the c.484T>C mutation of the VHL gene (stated as c.697T>C in the paper which used the Latif sequence as reference). Peripheral blood lymphocytes were collected and products of the polymerase chain reaction performed on this sample were analyzed with single-stranded conformational polymorphism analysis (SSCP), PCR sequencing and Southern analysis. This missense mutation was confirmed using restriction fragment length polymorphism or allele-specific oligonucleotide analysis. This patient has no family history of clinical VHL features. The patient presented with renal cell carcinoma.

A previous study of 26 Japanese, VHL families was extended to 41 additional families. Germline mutations were detected in 55 of 77 Japanese families using SSCP, direct sequencing, and Southern Blot analysis of peripheral blood samples. The C162R (c.484T>C) germline mutation of the VHL gene was found in a VHL type 1 family of 6 presenting with CNS hemangioblastoma (1/6), retinal angioma (2/6), renal cell carcinoma (3/6) and pancreatic tumor or cyst (unspecified) (1/6) (family ID 4). This family was previously reported in PMID 8634692.

PatientID:6

KindredID: 6

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo:None.

CohortInfo:Between September 1994 and December 1997, 16 unrelated individuals were referred to Genetic Services of Western Australia by local clinicians and by similar genetic services in other States, for VHL gene mutation analysis because of clinical manifestations suggestive of the diagnosis.

CasePresentingHPOs: HP:0005584 (renal cell carcinoma)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0002666, HP:0005584, HP:0009711, HP:0010797(pheochromocytoma, pancreatic cysts, retinal capillary hemangioma, hemangioblastoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.C162R (c.484T>C)

LegacyVariant:p.C162R (c.697T>C)

CaseProblemVariantFreeText: N/A

ClinVarID: 496067 https://www.ncbi.nlm.nih.gov/clinvar/variation/496067/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName:C162R (c.484T>C)

MultipleGeneVariants: N/A

PatientID: 7

KindredID: 7

Case: F, 30Y0M, Korean

DiseaseAssertion: VHL

FamilyInfo: None. Sporadic

CasePresentingHPOs: HP:0010797; HP:0009711; HP:0005584 (hemangioblastoma, retinal capillary hemangioma, renal cell carcinoma)

CaseHPOFreeText: Bilateral involvements of renal cell carcinomas (See table 1). 'Other' phenotypes found in patient. These are noted in the paper to include: pancreatic neuroendocrine tumors (PNETs), renal and pancreatic cysts and central nervous system tumors, although it is not clearly stated that patient has all. (See Table 1).

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.C162R (c.484T>C)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVar: 496067 https://www.ncbi.nlm.nih.gov/clinvar/variation/496067/

CAID: CA351756117 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.484T%3EC

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: C162R (c.484T>C)

MultipleGeneVariants: N/A

Germline mutations in 45 unrelated Japanese VHL patients were determined from blood samples using PCR-SSCP or Southern blot analyses. The authors reported a nucleotide deletion (i.e. 697T>C) which coincides with legacy variant nomenclature (AF010238.1) and was mapped to c.484T>C (NM_000551.3). PCR-SSCP or Southern blot analyses of the DNA from family members showed that mutations were segregated with disease phenotype in VHL families, although this data was not shown. Data on the presence of retinal angioma, CNS hemangioblastoma (Hb) renal cell carcinoma (RCC), and pheochromocytoma was available. Case 4 had a C162R (c.484T>C) mutation. 2 members were affected: both had RCC, 1 had retinal angioma, and 1 had CNS Hb. We were not able to determine which member had more than one phenotype. Other demographics of the members were not described.