93 families examined at the Clinical Center of the National Institutes of Health (Bethesda, MD) underwent genetic testing for germline mutations of the VHL gene. Whole blood was extracted and genomic DNA was amplified by PCR and products were sequences using a cycle sequencing kit with dye-labeled terminators and automatically sequenced. This missense mutation was found in a VHL type 1 family (lineage 128). The variant was reported as c.470C>G (AF010238.1) and was mapped to P86R (c.257C>G) (NM_000551.3).

GroupID: None

DiseaseAssertion: VHL

GroupSize: 4

GroupNumberMales:N/A

GroupNumberFemales:N/A

GroupEthnicity: N/A

GroupAgeRange: ≥12

GroupInfo: The four patients were grouped by mutation.

GroupPresentingHPOs: HP:0001732 (abnormality of the pancreas)

GroupHPOFreeText: N/A

GroupNotHPOs:N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.P86R(c.257C>G)

LegacyVariant:N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223170 https://www.ncbi.nlm.nih.gov/clinvar/variation/223170/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: P86R(c.257C>G)

MultipleGeneVariants: N/A

A case report revealed a 47Y female patient with two synchronous kidney tumors on the right side that were clear cell renal cell carcinoma and cystic renal cell carcinoma, and a clear cell pancreatic neuroendocrine tumor. She also presented with multiple pancreatic and renal cysts. Genetic analysis confirmed a c.257C>G (p.Pro86Arg) mutation in the VHL gene. The patient had a positive family history with their mother and brother having VHL disease, but genotypic and phenotypic information for family members was not available.

Fourty-four of 389 patients with VHL (between 1988-1999) screened positive for PNETs either by pathologic analysis of tissue specimens or by characteristic radiographic appearance on CT and MRI. VHL gene germline mutations were determined by quantitative Southern blotting to detect deletions of the gene and gene rearrangements as well as complete gene sequencing. Patient 18, a 19 year old female, was found to harbour the c.257C>G mutation in the VHL gene (stated as 470 C to G in the paper which used Latif sequence as reference) leading to an amino acid change of Pro to Arg at protein position 86. She presented with a single radiologic pancreatic neuroendocrine tumor. ACMG evidence codes: 'PP4' since the patient presents phenotypes highly specific for a disease with a single genetic etiology.

PatientID: None

KindredID: 3

Case: M, 22Y0M, Ethnicity Unknown

DiseaseAssertion: Clear Cell Renal Cell Carcinoma

FamilyInfo: N/A

CohortInfo: The National Cancer Institute has a frozen tumour bank of ccRCC tumours that have been removed from VHL patients. We selected six patients, three males and three females, with at least five tumours from a single surgery from one kidney.

CasePresentingHPOs: HP:0006770 (clear cell renal cell carcinoma)

CaseHPOFreeText: One of the samples from this patient had few variants and clustered with the normal samples. Further inspection showed these samples were cyst-like rather than tumours, so they were excluded from further analysis. This suggests that the patient had renal cysts alongside ccRCC at age 22.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.P86R(c.257C>G)

LegacyVariant:N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223170 https://www.ncbi.nlm.nih.gov/clinvar/variation/223170/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: P86R(c.257C>G)

MultipleGeneVariants: N/A