PatientID: III-9

KindredID: 1

Case: F, Age Unknown, Middle Eastern

DiseaseAssertion: VHL

FamilyInfo: Multigenerational Kuwaiti family with Arabian and Persian genetic admixture. Thirteen members of the family had been clinically diagnosed as having VHL. Patient 1-I had 6 children, 5 of which were found with VHL and the p.W117C mutation. 7/20 of her grandchildren also found to have VHL and the same mutation.

CasePresentingHPOs: HP:0010797; HP:0006770; HP:0009713; HP:0009711; HP:0006880 (hemangioblastoma; clear cell renal cell carcinoma; spinal hemangioblastoma; retinal capillary hemangioma; cerebellar hemangioblastoma)

CaseHPOFreeText: Member had clear cell renal carcinomas in addition to hemangioblastomas. She had undergone multiple surgeries because of tumors involving the cerebellum, cervical spine, lumbar spine, multiple abdominal and pelvic organs and the retina. The tumor had been demonstrated on angiography as very extensive and vascular. The patient had had a partial nephrectomy, adrenalectomy, distal pancreatomy for involvement of the tail of the pancreas with a hemangioblastoma and a left salpingoophorectomy.

CaseNotHPOs: HP:0002666 (pheochromocytoma)

CaseNotHPOFreeText: Lacked evidence of any pheos.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.W117C (c.351G>T)

LegacyVariant: p.Trp117Cys (c.564G>T)

CaseProblemVariantFreeText: N/A

ClinVarID: 167827 https://www.ncbi.nlm.nih.gov/clinvar/variation/167827/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: W117C (c.351G>T)

MultipleGeneVariants: N/A

PatientID: III-8

KindredID: 1

Case: F, Age Unknown, Middle Eastern

DiseaseAssertion: VHL

FamilyInfo: Multigenerational Kuwaiti family with Arabian and Persian genetic admixture. Thirteen members of the family had been clinically diagnosed as having VHL. Patient 1-I had 6 children, 5 of which were found with VHL and the p.W117C mutation. 7/20 of her grandchildren also found to have VHL and the same mutation.

CasePresentingHPOs: HP:0010797; HP:0006770; HP:0009725; HP:0030692 (hemangioblastoma; clear cell renal cell carcinoma; bladder tumour; brain tumour)

CaseHPOFreeText: Member had clear cell renal carcinomas in addition to hemangioblastomas. She was also the only member of the family to be diagnosed as having a bladder tumor, considered rare in VHL cases, and a brain tumor.

CaseNotHPOs: HP:0002666 (pheochromocytoma)

CaseNotHPOFreeText: Lacked evidence of any pheos.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.W117C (c.351G>T)

LegacyVariant: p.Trp117Cys (c.564G>T)

CaseProblemVariantFreeText: N/A

ClinVarID: 167827 https://www.ncbi.nlm.nih.gov/clinvar/variation/167827/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: W117C (c.351G>T)

MultipleGeneVariants: N/A

PatientID: III-7

KindredID: 1

Case: M, Age Unknown (deceased), Middle Eastern

DiseaseAssertion: VHL

FamilyInfo: Multigenerational Kuwaiti family with Arabian and Persian genetic admixture. Thirteen members of the family had been clinically diagnosed as having VHL. Patient 1-I had 6 children, 5 of which were found with VHL and the p.W117C mutation. 7/20 of her grandchildren also found to have VHL and the same mutation.

CasePresentingHPOs: HP:0010797; HP:0006770 (hemangioblastoma; clear cell renal cell carcinoma)

CaseHPOFreeText: Member had clear cell renal carcinomas that were the main cause of mortality, in addition to hemangioblastomas

CaseNotHPOs: HP:0002666 (pheochromocytoma)

CaseNotHPOFreeText: Lacked evidence of any pheos.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.W117C (c.351G>T)

LegacyVariant: p.Trp117Cys (c.564G>T)

CaseProblemVariantFreeText: N/A

ClinVarID: 167827 https://www.ncbi.nlm.nih.gov/clinvar/variation/167827/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: W117C (c.351G>T)

MultipleGeneVariants: N/A

GroupID/ KindredID: 13F, 564NCI, 1239NCI

DiseaseAssertion: VHL

GroupSize: N/A

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: This germline familial VHL mutation was taken from the Neuro Olcologie database in Paris and the National Cancer Institute database, with an unknown number of members belonging to Family IDs 13F, 564NCI, 1239NCI. Table 3 lists all ID and mutations associated with individuals possessing renal carcinoma, without pheochromocytoma.

GroupPresentingHPOs: HP:0005548 (renal cell carcinoma)

GroupHPOFreeText: Described as a VHL family with RCC, without pheochromocytoma. Other phenotypes are likely, however not detailed in this publication

GroupNotHPOs: HP:0002666 (pheochromocytoma)

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: 7728151; 9829911

SupplementalData: N/A

Variant: p.W117C (c.351G>T)

LegacyVariant: p.W117C (c.564G>T)

CaseProblemVariantFreeText: N/A

ClinVarID: 167827 https://www.ncbi.nlm.nih.gov/clinvar/variation/167827/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: W117C (c.351G>T)

MultipleGeneVariants: N/A

PatientID: N/A

KindredID: 198

Case: Age unknown, Sex unknown, Ethnicity unknown

DiseaseAssertion: assumed VHL

FamilyInfo: Paper states: Germline, de novo

CasePresentingHPOs: HP:0010797 (hemangioblastoma)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Yes (Specifically Supp. Table S2)

Variant: p.W117Cfs*42 (c.351del)

LegacyVariant: N/A

CaseProblemVariantFreeText: paper states c.350delG which automaps to NM_000551.3:c.351delG

ClinVarID: 223197 https://www.ncbi.nlm.nih.gov/clinvar/variation/223197/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: W117fs (c.351del)

MultipleGeneVariants: N/A