Analysis of peripheral blood samples from 5 Japanese families with PCR and SSCP revealed 4 germline mutations. This missense mutation NM_000551.3:c.484T>C was found in a family of seven individuals. Please note that the paper states the mutation as c.697T>C because it uses a legacy reference sequence. Two VHL patients were identified; the patients were siblings, and one presented with brain stem hemangioblastomas and retinal angiomas while the other presented with renal cell carcinoma (family D). Single-strand conformational polymorphism (SSCP) analysis showed bands for the 2 affected individuals that were absent from 5 normal individuals. Direct sequencing was performed on SSCP positive patients.

PatientID: 5

KindredID: D

Case: M, Age Unknown, Japanese

DiseaseAssertion: Assumed VHL

FamilyInfo: The patient’s family consisted of seven members, but only the patient’s sister carried the same missense variant NM_000551.3:c.484T>C the patient carried and developed symptoms.

CasePresentingHPOs: HP:0005584; HP:0011513 (Renal cell carcinoma, retinal angioma)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

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

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

ClinVarID: N/A

CAID: CA351756117, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA351756117

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