PatientID: 56

KindredID: None

Case: Age and Sex unknown, Chinese

DiseaseAssertion: VHL

FamilyInfo: None

CasePresentingHPOs: HP:0010797; HP:0001737; HP:0000107; HP:0009711; HP:0005584 (hemangioblastoma, pancreatic cysts, renal cyst, retinal capillary hemangioma, renal cell carcinoma)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0002666; HP:0030405; HP:0030393 (Pheochromocytoma, Pancreatic endocrine tumour, Endolymphatic sac tumour)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Yes; See Suppl 1 (Supporting table)

Variant: p.N131K (c.393C>G)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: CA351753948 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.393C%3EG

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: N131K (c.393C>G)

MultipleGeneVariants: N/A

PatientID: V233

KindredID: V233

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: One unaffected family members were tested and found to be negative. No other family history was available.

CohortInfo: 92 unrelated patients with VHL disease.

CasePresentingHPOs: HP:0002666 (pheochromocytoma)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.N131K(c.393C>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 420074 https://www.ncbi.nlm.nih.gov/clinvar/variation/420074/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName:N131K(c.393C>A)

MultipleGeneVariants: N/A

GroupID: 233

DiseaseAssertion: VHL

GroupSize: 2

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: French

GroupAgeRange: N/A

GroupInfo: 2 members of this family were found to harbor the c.393C>A germline variant of the VHL gene. Member 5114 had no renal involvement. Member 5112 presented with mild renal disease. Families were recruited from the French VHL Registry. Enrolment in the study required identification of the germline VHL mutation (currently 85% of the families included in the French VHL Registry) and available data regarding renal phenotype. A total of 126 families fulfilled these criteria.

GroupPresentingHPOs: HP:0009726 (Renal neoplasm)

GroupHPOFreeText: Mild renal disease (simple renal cyst, multicystic kidney[s], small lesion [less than 10 mm in size] of unknown significance, or small solid tumor without indication for surgical removal [less than 30 mm in size]).

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: Paper states that this family is previously reported in PMID 9829912, where 1 individual with this mutation is reported. It is unclear which of the members of this family this previously reported patient corresponds to.

SupplementalData: Phenotype and genotype information can be found in Supplementary Table S1.

Variant: p.N131K (c.393C>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 420074, https://www.ncbi.nlm.nih.gov/clinvar/variation/420074/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: N131K (c.393C>A)

MultipleGeneVariants: N/A

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

PatientID: III:2 (case)

KindredID: 1

Case: F, 49Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: VHL disease was diagnosed in her relatives - although no genetic testing was directly performed on them prior to death. 2/3 of her siblings and her father were affected. Her father had retinal hemangioblastoma at 30Y, CNS hemangioblastoma at 40Y and died at 41Y. Her older brother had kidney cancer and died at 48Y, and her sister had retinal hemangioblastoma at 13Y and CNS hemangioblastoma at 29Y. The case’s daughter tested negative and their other living sister.

CasePresentingHPOs: HP:0009711; HP:0000107; HP:0009713; HP:0002668 (retinal capillary hemangioblastoma; renal cysts; spine hemangioblastoma; paraganglioma)

CaseHPOFreeText: patient at retinal hemangioblastoma at 22Y. At 47Y she reported pains in her second and third finger of the right hand. She developed large carotid body paraganglioma at the common carotid artery bifurcation, (49Y) coexisting with a hemangioblastoma situated intramedullary in region C5/C6 (the right-sided dorsal part of the spinal cord) at 47Y). 1 year after the hemangioblastoma resection, the spinal symptoms receded and the carotid body paraganglioma still was asymptomatic. Motor issues and Babinski syndrome were also observed.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.N131K (c.393C>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 420074 https://www.ncbi.nlm.nih.gov/clinvar/variation/420074/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: N131K (c.393C>A)

MultipleGeneVariants: N/A