proband (III-2
PatientID: III-2
KindredID: 1
Case: M, 62Y0M, Ethnicity Unknown
DiseaseAssertion: VHL
FamilyInfo: His mother (II,2) did not carry the mutation. His father (II-1) died age 42 from a cerebellar hemangioblastoma, while his paternal grandparents died at an advanced age and had no known history of VHL manifestations. His brother (III,1) did not harbour the mutation. The patient and his wife (III,3) who did not carry the mutation, had 3 daughters; two with the mutation and one without. Two of his daughters who carried the mutation, aged 28 and 36 (IV-2, IV-3), had a personal history of CNS and retinal hemangioblastomas. Patient IV-2 recently developed a ccRCC and a pheochromocytoma, and patient IV-3 a pancreatic neuroendocrine tumor. Refer to pedigree in Figure 1.
CasePresentingHPOs: HP:0006770, HP:0010797, HP:0009711 (clear cell renal cell carcinoma, hemangioblastoma, retinal capillary hemangioma)
CaseHPOFreeText: The patient died at age 62 of CNS complications.
CaseNotHPOs: HP:0002666, HP:0030405 (pheochromocytoma, pancreatic endocrine tumour)
CaseNotHPOFreeText: No erythrocytosis; the hematocrit, red blood cells count and Epo levels were all normal.
CasePreviousTesting: N/A
PreviouslyPublished: N/A
SupplementalData: Yes supplemental data and figures. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555745/bin/NIHMS881280-supplement-Supplemental_Data.pdf
Variant: p.R200W (c.598C>T)
LegacyVariant: N/A
CaseProblemVariantFreeText: N/A
ClinVarID: 2232 https://www.ncbi.nlm.nih.gov/clinvar/variation/2232/
CAID: CA020510 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.598C%3ET
gnomAD: 0.0002016 https://gnomad.broadinstitute.org/variant/3-10191605-C-T
VariantEvidence: The patient was a heterozygous carrier of a single R200W and R161Q mutation (both on the same VHL allele).
MutationType: missense_variant;transition
CivicName:R200W(c.598C>T) and R161Q(c.482G>A)
MultipleGeneVariants: Germline, VHL, c.482G>A (p.Arg161Gln)