PatientID: III-4

KindredID: 1

Case: 34Y0M, Sex and Ethnicity Unknown

DiseaseAssertion: pheochromocytoma

FamilyInfo: Family suggesting incomplete penetrance of a VHL gene germline mutation. Mutation (p.R64P) was found in a family with 6 patients total with three generations. The earliest patient described (I-1) presented with renal cell carcinoma (age at diagnosis 48 years), 1 of their 6 children (II-1) at age 59 had no typical VHL manifestations after annual clinical monitoring and suggest non-penetrance in the patient; the second of 6 children (II-3), then aged 51, had bilateral pheochromocytoma diagnosed age 14. Their only child (III-5) had a paraganglioma with an age of diagnosis of 29 years, and a renal cyst. Patient II-1 had 4 children - one (III-1; aged 40) who presented as a carrier with no typical VHL manifestations after annual clinical monitoring; and another 32 years old presenting with pheochromocytoma. (See Figure 2 for pedigree)

CasePresentingHPOs: HP:0002666 (pheochromocytoma)

CaseHPOFreeText: Bilateral pheochromocytoma diagnosed at age 34

CaseNotHPOs: N/A

CaseNotHPOFreeText: Unclear as to whether testing for other manifestations was conducted

CasePreviousTesting: N/A

PreviouslyPublished: Previously reported, HGMD (Human Gene Mutation Database: http://uwcmml1s.uwcm.ac.uk/uwcm/mg/search/120488.html)

SupplementalData: N/A

Variant: p.R64P (c.191G>C)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 2226 https://www.ncbi.nlm.nih.gov/clinvar/variation/2226/

CAID: CA020089 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.191G%3EC

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: R64P (c.191G>C)

MultipleGeneVariants: N/A