PatientID: II-26

KindredID: 1

Case: M, 45Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Large multigenerational family with a history of both VHL and spinocerebellar ataxia type 2 (SCA2). Screening for clinical and genetic diagnostics were gathered as well as thorough information on non-living members. His two daughters also appeared to have the VHL mutation. See family pedigree (Fig. 1).

CasePresentingHPOs: HP:0006880; HP:0009711; HP:0006770; HP:0009713; HP:0002031; HP:0003396; HP:0001649; HP:0001737; HP:0030424 (cerebellar hemangioblastoma, retinal capillary hemangioma, clear cell renal cell carcinoma, spinal hemangioblastoma, Abnormal esophagus morphology, Syringomyelia, Tachycardia, pancreatic cysts, epididymal cyst)

CaseHPOFreeText: CNS (including retinal angiomas) and renal involvement; with cerebellum hemangioblastoma found at age 34Y. An oesophageal abnormality that was treated with vagotomy at age 35Y. At age 44Y had bilateral clear cell renal cancer resulting in a right partial nephrectomy and left total nephrectomy. Same year had spinal surgery to treat a syrinx associated with a spinal cord haemangioblastoma, as well as cystic lesions in the pancreas (consistent with epididymal cystadenoma).

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.E160Sfs*10 (c.477delA)

LegacyVariant: c.688delA

CaseProblemVariantFreeText: c.477del, p.Glu160Serfs10 should be used. Details: 477del same as 475delA bc that codon is AAA so doesn't matter which A gets deleted: there is an A at 475 476 477 so for HGVS we say that 477 (the latter) is deleted since that follows HGVS nomenclature. Thus use c.477del: p.Glu160Serfs10

ClinVarID: 182959 https://www.ncbi.nlm.nih.gov/clinvar/variation/182959/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: E160fs (c.477del)

MultipleGeneVariants: N/A

PatientID: II:4 (proband 5’s sister 2)

KindredID: 5

Case: F, 34Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: Her father and two sisters presented with this same mutation. The father had RCC diagnosed at 54Y. The one sister (II:3) had had pancreatic tumors at 36Y and hemangioblastomas at 38Y. The brother (II:1) appeared to be non-affected, while the other sister (II:2) had hemangioblastoma, renal cell carcinoma, pancreatic cysts, and Papillary cystadenoma of the epididymis diagnosed at 37Y; and pheochromocytoma at 39Y

CasePresentingHPOs: HP:0009711 (retinal capillary angiomas)

CaseHPOFreeText: had retinal angiomas at 34Y

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R167W (c.499C>T)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 2218 (https://www.ncbi.nlm.nih.gov/clinvar/variation/2218/)

CAID: N/A

gnomAD: 0.000007954 https://gnomad.broadinstitute.org/variant/3-10191506-C-T

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: R167W (c.499C>T)

MultipleGeneVariants: N/A