This study retrospectively reviewed the nephrectomy specimens for 20 patients, for whom histologic slides were available, from the authors respective institutes’ VHL clinics over a 15-year period (1996 to 2011). One patient (case 3) was found to have a history of VHL disease with a confirmed germline missense mutation (p.L128P (c.383T>C)) of the VHL gene. The 38 year old female proband presented with multiple bilateral renal tumors, and underwent multiple partial nephrectomies with tumor enucleations. Six of such tumors were identified and they ranged in size from 0.4-6.5 cm. Of these, 4 tumors were CCRCCs and 2 tumors showed were diagnosed as CCPRCCs confined to the kidney. Further, the tumors were classified as hemangioblastomas. ACMG evidence codes: 'PP4' since the patient presents phenotypes highly specific for a disease with a single genetic etiology.

PatientID: 5

KindredID: 5

Case: F, 27Y0M, Korean

DiseaseAssertion: VHL

FamilyInfo: None. Sporadic

CasePresentingHPOs: HP:0010797; HP:0005584 (hemangioblastoma, renal cell carcinoma)

CaseHPOFreeText: '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.L128P (c.383T>C)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 1208816 https://www.ncbi.nlm.nih.gov/clinvar/variation/1208816

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: L128P (c.383T>C)

MultipleGeneVariants: N/A

PatientID: 30

KindredID: 30

Case: F, 27Y0M, Korean

DiseaseAssertion: VHL

FamilyInfo: No family history of VHL.

CohortInfo: 26 Korean patients with more than one HAB in the CNS or eye, a single HAB in the CNS or retina plus a visceral manifestation (multiple renal, pancreatic or hepatic cysts, pheochromocytoma and RCC) and positive family history plus any one of the above manifestations.

CasePresentingHPOs: HP:0010797; HP:0005584 (Hemangioblastoma, Renal cell carcinoma)

CaseHPOFreeText: CNS hemangioblastoma. Other phenotypes presented but not specified (one or more of: pancreatic cyst or tumor, renal or hepatic cyst). Diagnosed with VHL Type 1. Phenotypes revised from previous reports (see “PreviouslyPublished” section below for PMID).

CaseNotHPOs: HP:0002666; HP:0009711 (Pheochromocytoma, Retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 19270817

SupplementalData: N/A

Variant: p.L128P (c.383T>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 1208816, https://www.ncbi.nlm.nih.gov/clinvar/variation/1208816/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: L128P (c.383T>C)

MultipleGeneVariants: N/A