Two Swedish families with von Hippel-Lindau disease (VHL) were analyzed. Family A was previously reported (PMID 7700111; Wiklund et al., 1995) and the following provides an update on the family. Family A consists of 21 individuals over four generations, 8 of which are carriers, affected by, or suspected to be affected by VHL disease. 3 of the 8 members had died from VHL related tumors, and it is unclear if they were genetically tested for the family mutation. Genetic analysis from available blood samples revealved a germline familial VHL frameshift mutation S183fs (c.548delC, originally written in paper as legacy notation c.761delC). The remaining 5 of the 8 family members were found with this mutation, identifying 3 individuals with VHL disease, 1 individual who developed VHL disease during the time of the study (renal carcinoma and symptomatic cerebellar hemangioma), and 1 asymptomatic carrier. Individual patient phenotypic and demographic data was not available. The paper does describe that overall, 5 of the 8 family members had renal carcinoma, 5/8 multiple cerebellar hemangiomas, 2/8 angiomatosis retinae and 1/8 had an epidymidal tumor. ACMG: PP4 PP1

PatientID: 9

KindredID: 9

Case: M, 18Y0M, Ethnicity Unknown

DiseaseAssertion: Cerebellar Hemangioblastoma

FamilyInfo: N/A

CohortInfo: The cohort included a series of 20 capillary haemangioblastomas of the central nervous system for mutations of the VHL gene.

CasePresentingHPOs: HP:0006880 (cerebellar hemangioblastoma)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.S183Cfs*19(c.548delC)

LegacyVariant: p.S183Cfs*19(c.761delC)

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA658795184 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.548delC

gnomAD: N/A

VariantEvidence: Refer to Table 1 for abnormal SSCP or heteroduplex patterns.

MutationType: minus_1_frameshift_variant

CivicName: S183fs (c.548delC)

MultipleGeneVariants: N/A

GroupID/ KindredID: A

DiseaseAssertion: assumed VHL

GroupSize: 8

GroupNumberMales: 2

GroupNumberFemales: 6

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: The kindred comprised of 21 individuals over 4 generations. The following members have a confirmed mutation: I:1 (F, deceased), II:2 (F, deceased), III:2 (F, deceased), III:4 (M), III:6 (F), IV:4 (F), IV:6 (M), IV:7 (F, is predicted to be affected). The 3 deceased members had died from VHL related tumors. Another 3 were suffering from VHL, another developed RCC an cHB, and 1 was a VHL carrier. All 8 members had this mutation

GroupPresentingHPOs: HP:0005584; HP:0006880; HP:0009711; HP:0030421 (renal cell carcinoma; cerebellar hemangioblastoma; retinal capillary hemangioma; epidymidal tumor)

GroupHPOFreeText: 5 members had RCC, 5 had multiple cerebellar hemangioblastomas, 2 had retinal capillary hemangioma and 1 had an epidymidal tumor.

GroupNotHPOs: HP:0002666 (pheochromocytoma)

GroupNotHPOFreeText: None of the eight VHL carriers of the first kindred had developed pheochromocytoma, and this kindred clearly presents VHL disease type 1

GroupPreviousTesting: N/A

PreviouslyPublished: 7700111

SupplementalData: N/A

Variant: p.S183Cfs*19 (c.548delC)

LegacyVariant: p.183 (c.761delC)

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA658795184 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.548delC

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: S183fs (c.548delC)

MultipleGeneVariants: N/A