Two Swedish families with von Hippel-Lindau disease (VHL) were analyzed. Family B consists of 4 members across 2 generations. Patient I:1 (proband) is a female with renal cell carcinoma and cerebellar hemangioblastomas. Genetic analysis of blood samples revealed a frameshift mutation N174fs (c.520insAA, originally written in paper was legacy notation c.732insAA) with a downstream premature stop codon at position 201. Genetic analysis of her two children also confirmed the mutation: her son, patient II:1, had cerebellar hemangioblastoma and her daughter, patient II:2, was asymptomatic. The proband's partner (I:2) had no mutation and no VHL phenotype. ACMG: PP4

GroupID/ KindredID: B

DiseaseAssertion: assumed VHL

GroupSize: 3

GroupNumberMales: 1

GroupNumberFemales: 2

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: 3 members: mother (I:1) and her two children, II:1 (M) and II:2 (F) - Each proved to hold the mutation. II:2 was a predicted asymptomatic carrier. The mother (proband) was considered to carry a new mutation.

GroupPresentingHPOs: HP:0005584; HP:0006880 (renal cell carcinoma; cerebellar hemangioblastoma)

GroupHPOFreeText: The mother (I:1) had RCC and a cerebellar hemangioblastoma. Her son II:1 had a cerebellar hemangioblastoma.

GroupNotHPOs: N/A

GroupNotHPOFreeText: The daughter (II:2) is devoid of know manifestations

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.N174KFS*29 (c.519insAA)

LegacyVariant: p.174FS (c.732insAA)

CaseProblemVariantFreeText: c.519insAA corrects to NM_000551.3:c.520_521dupAA

ClinVarID: N/A

CAID: CA2573051315 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2573051315

gnomAD: N/A

VariantEvidence: N/A

MutationType: plus_2_frameshift_variant; duplication

CivicName: N174FS*29 (c.519insAA)

MultipleGeneVariants: N/A