PatientID: 10 (Uncle)

KindredID: 7

Case: M, 36Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: 6 members of this family were found to harbor the c.319C>G germline variant of the VHL gene. ID 11 presented with renal and pancreatic abnormalities, pheochromocytoma and other undefined phenotypes. ID 1 presented with pheochromocytoma. ID 2 presented with pancreatic abnormalities. ID 24 presented with renal abnormalities, and pheochromocytoma, and died at age 62. ID 4 presented with pheochromocytoma.

CasePresentingHPOs: HP:0002666; HP:0001732; HP:0010797 (Pheochromocytoma, Abnormality of the pancreas, Hemangioblastoma)

CaseHPOFreeText: The patient presented with CNS hemangioblastoma (31Y, 35Y), pancreatic abnormalities (31Y) and pheochromocytoma (13Y).

CaseNotHPOs: HP:0009711; HP:0005584; HP:0000077 (Retinal capillary hemangioma, Renal cell carcinoma, Abnormality of the kidney)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table 1.

Variant: p.R107G (c.319C>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 43599, https://www.ncbi.nlm.nih.gov/clinvar/variation/43599/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: R107G (c.319C>G)

MultipleGeneVariants: N/A

PatientID: 22

KindredID: 22

Case: 13Y0M, Sex Unknown, Argentinian

DiseaseAssertion: hemangioblastoma

FamilyInfo: No family history

CasePresentingHPOs: HP:0010797 (hemangioblastoma)

CaseHPOFreeText: Aged 13Y at diagnosis (genetic testing); does not fulfil type 1 VHL clinical diagnosis. Solitary CNS angiomas diagnosed at 13Y (See Table 1 & 2).

CaseNotHPOs: N/A

CaseNotHPOFreeText: did not develop other manifestations of the disease during a 5- year follow-up.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.W88* (c.264G>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 936684 https://www.ncbi.nlm.nih.gov/clinvar/variation/936684/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: stop_gained

CivicName: W88* (c.264G>A)

MultipleGeneVariants: N/A

PatientID: II

KindredID: 15

Case: Sex Unknown, 53Y0M, Danish

DiseaseAssertion: VHL

FamilyInfo: 2 other family members presented with the same VHL variant. Patient 15-I was asymptomatic. Patient 15-III presented with 2 pheochromocytoma (15Y).

CasePresentingHPOs: HP:0002666; HP:0010797; HP:0009711 (Pheochromocytoma, Hemangioblastoma, Retinal capillary hemangioma)

CaseHPOFreeText: Diagnosed with VHL at age 8Y. Presented with 2 pheochromocytoma (8Y) 2 CNS hb (12Y and 13Y) and 2 retinal hemangioblastomas (8Y, 12Y). Age at the end of study: 53Y.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.V166F (c.496G>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 2224, https://www.ncbi.nlm.nih.gov/clinvar/variation/2224/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: V166F (c.496G>T)

MultipleGeneVariants: N/A

PatientID: III:7

KindredID: 7

Case: M, 13Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: 8 other members of this 3 generation family were observed to be affected with various presentations of VHL. This patient’s father and 3 cousins were confirmed with identical mutations. DNA samples were not available for all members in the family however.

CasePresentingHPOs: HP:0010797 (hemangioblastoma)

CaseHPOFreeText: had hemangioblastoma at 13Y

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.W117G (c.349T>G)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 862346 https://www.ncbi.nlm.nih.gov/clinvar/variation/862346/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: W117G (c.349T>G)

MultipleGeneVariants: N/A

PatientID: I

KindredID: 12

Case: Sex Unknown, 21Y0M, Danish

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0009711; HP:0010797; HP:0001737 (Retinal capillary hemangioma, Hemangioblastoma, Pancreatic cysts)

CaseHPOFreeText: Diagnosed with VHL at age 5Y. Presented with 5 retinal hemangioblastoma (5Y, 13Y, 14Y) 6 CNS hemangioblastoma (15Y, 17Y) 3 pancreatic cysts (15Y). Age at the end of study: 21Y.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: Exon 1-2 Deletion (c.1-?_463+?del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: exon_loss_variant

CivicName: Exon 1-2 Deletion

MultipleGeneVariants: N/A