PatientID: 84

KindredID: 84

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: Assumed VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0002666 (Pheochromocytoma)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Patient information pulled from Supplemental Table 1b.

Variant: p.R107H (c.320G>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223184, https://www.ncbi.nlm.nih.gov/clinvar/variation/223184/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: R107H (c.320G>A)

MultipleGeneVariants: N/A

PatientID: 63

KindredID: 63

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0030405; HP:0100634 (pancreatic neuroendocrine neoplasm, Neuroendocrine neoplasm)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0010797; HP:0009711; HP:0030421; HP:0006770 (hemangioblastoma; retinal capillary hemangioma; Epididymal neoplasm, clear cell renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 29437867 (Family 7 - see here for more info)

SupplementalData: Yes; see table S1 for VHL subject genetic and manifestation information.

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: 62

KindredID: 62

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0100634 (Neuroendocrine neoplasm)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0010797; HP:0030405; HP:0009711; HP:0030421; HP:0006770 (hemangioblastoma; pancreatic neuroendocrine neoplasm, retinal capillary hemangioma; Epididymal neoplasm, clear cell renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 29437867 (Family 7 - see here for more info)

SupplementalData: Yes; see table S1 for VHL subject genetic and manifestation information.

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: 61

KindredID: 61

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0010797; HP:0030405; HP:0009711; HP:0030421 (hemangioblastoma; pancreatic neuroendocrine neoplasm, retinal capillary hemangioma; Epididymal neoplasm)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0100634; HP:0006770 (Neuroendocrine neoplasm, clear cell renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 29437867 (Family 7 - see here for more info)

SupplementalData: Yes; see table S1 for VHL subject genetic and manifestation information.

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: 60

KindredID: 60

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0100634; HP:0030405; HP:0006770 (Neuroendocrine neoplasm, pancreatic neuroendocrine neoplasm, clear cell renal cell carcinoma)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0010797; HP:0009711; HP:0030421 (hemangioblastoma; retinal capillary hemangioma; Epididymal neoplasm)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 29437867 (Family 7 - see here for more info)

SupplementalData: Yes; see table S1 for VHL subject genetic and manifestation information.

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

GroupID: 7

DiseaseAssertion: VHL

GroupSize: 5

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: Family of 5 VHL Type 1 affected individuals.

GroupPresentingHPOs: HP:0009711; HP:0010797; HP:0005584; HP:0002668 (Retinal capillary hemangioma, Hemangioblastoma, Renal cell carcinoma, Paraganglioma)

GroupHPOFreeText: CNS hemangioblastoma (4/5 affected members), renal carcinoma (2/5 affected members) and retinal angioma (3/5 affected members). The proband presented with one tumor which biopsy showed to be a non-functional paraganglioma

GroupNotHPOs: HP:0002894; HP:0002666 (Neoplasm of the pancreas, Pheochromocytoma)

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R107P (c.320G>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 36900, https://www.ncbi.nlm.nih.gov/clinvar/variation/36900/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: R107P (c.320G>C)

MultipleGeneVariants: N/A

PatientID: 2 (Sister)

KindredID: 7

Case: F, 11Y0M, 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 24 presented with renal abnormalities, and pheochromocytoma, and died at age 62. ID 10 presented with CNS hemangioblastoma, pancreatic abnormalities and pheochromocytoma. ID 4 presented with pheochromocytoma.

CasePresentingHPOs: HP:0001732 (Abnormality of the pancreas)

CaseHPOFreeText: The patient presented with pancreatic abnormalities (9Y).

CaseNotHPOs: HP:0009711; HP:0005584; HP:0010797; HP:0002666; HP:0000077 (Retinal capillary hemangioma, Renal cell carcinoma, Hemangioblastoma, Pheochromocytoma, 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: I

KindredID: 8

Case: Sex Unknown, 35Y0M, Danish

DiseaseAssertion: VHL

FamilyInfo: N/A

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

CaseHPOFreeText: Diagnosed with VHL at age 15Y. Presented with 6 CNS hemangioblastomas (15Y) and 2 retinal hemangioblastomas (15Y). Age at the end of study: 15Y.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R107C (c.319C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351751195, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.319C%3ET

gnomAD: 0.000004522, https://gnomad.broadinstitute.org/variant/3-10183850-C-T?dataset=gnomad_r2_1

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: R107C (c.319C>T)

MultipleGeneVariants: Germline, VHL, c.353T>C (p.L118P)

PatientID: 5

KindredID: 5

Case: F, 50Y0M, Ethnicity Unknown

DiseaseAssertion: assumed VHL

FamilyInfo: Positive family history. Her mother suffered from blindness of one eye potentially due to retinal angiomatosis and was operated for a left adrenal pheochromocytoma. Her uncle died due to renal cell carcinoma and had spinal hemangioblastomas. All three of her sons are carriers of the mutation, one of whom was operated for a right adrenal pheochromocytoma at age 24 and a left adrenal pheochromocytoma at age 32. Screening of the 27-yr-old son revealed asymptomatic retinal and spinal hemangioblastomas.

CohortInfo: An international consortium registered patients with head and neck paragangliomas with VHL or RET gene mutations.

CasePresentingHPOs: HP:0002668; HP:0006748; HP:0009711; HP:0009713 (paraganglioma, adrenal pheochromocytoma, retinal capillary hemangioma, spinal hemangioblastoma)

CaseHPOFreeText: At 37Y she noted a mass at the left side of her neck. MRI disclosed a 3-cm carotid body tumor (paraganglioma). At age 50, the patient was operated for a left adrenal pheochromocytoma. Clinical screening for VHL showed asymptomatic retinal and spinal hemangioblastomas.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R107H (c.320G>A)

LegacyVariant: p.R107H

CaseProblemVariantFreeText: As the publication only provides the p., the mutation was deduced to p.R107H (c.320G>A)

ClinVarID: 223184 https://www.ncbi.nlm.nih.gov/clinvar/variation/223184/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: R107H (c.320G>A)

MultipleGeneVariants: N/A

GroupID: 30a

DiseaseAssertion: VHL

GroupSize: 4

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: a retrospective cohort study from an eye centre in Germany involved 148 VHL patients and their genetic data involved in retinal capillary hemangiomas.

GroupPresentingHPOs: HP:0009711 (retinal capillary hemangioma)

GroupHPOFreeText: These 4/5 patients with a R107H (c.320G>A) mutation had retinal capillary hemangiomas. Other VHL manifestations were discussed but not per- variant.

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.R107H (c.320G>A)

LegacyVariant: N/A

GroupProblemVariantFreeText: N/A

ClinVarID: 223184 https://www.ncbi.nlm.nih.gov/clinvar/variation/223184/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: R107H (c.320G>A)

MultipleGeneVariants: N/A

GroupID: 30b

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL CohortInfo: a retrospective cohort study from an eye centre in Germany involved 148 VHL patients and their genetic data involved in retinal capillary hemangiomas.

CasePresentingHPOs: N/A

CaseHPOFreeText: This was 1 of 5 patients discussed with this mutation. The individual did NOT have retinal hemangiomas; Other VHL manifestations were discussed but not per- variant.

CaseNotHPOs: HP:0009711 (retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Yes - Supplementary Table S1

Variant: p.R107H (c.320G>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223184 https://www.ncbi.nlm.nih.gov/clinvar/variation/223184/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: R107H (c.320G>A)

MultipleGeneVariants: N/A

PatientID: Father (of proband)

KindredID: 7

Case: M, 80Y0M, Chinese

DiseaseAssertion: renal cell carcinoma

FamilyInfo: Positive - His 2 children both had the same germline mutation. This first child (proband; sex unknown) had hemangioblastoma first presenting at 55Y, and their second child (son) was asymptomatic.

CasePresentingHPOs: HP:0005584 (renal cell carcinoma)

CaseHPOFreeText: asymptomatic upon genetic testing, but screening of VHL tumours after genetic testing revealed a left RCC with lung metastasis at 80Y

CaseNotHPOs: HP:0002666; HP:0009715; HP:0010797 (pheochromocytoma, Papillary cystadenoma of the epididymis, hemangioblastoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

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

CaseProblemVariantFreeText: N/A

LegacyVariant: 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: 1 (Proband)

KindredID: 7

Case: M, 12Y0M, 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 24 presented with renal abnormalities, and pheochromocytoma, and died at age 62. ID 2 presented with pancreatic abnormalities. ID 10 presented with CNS hemangioblastoma, pancreatic abnormalities and pheochromocytoma. ID 4 presented with pheochromocytoma.

CasePresentingHPOs: HP:0002666 (Pheochromocytoma)

CaseHPOFreeText: The patient presented pheochromocytoma (4Y).

CaseNotHPOs: HP:0009711; HP:0005584; HP:0001732; HP:0010797; HP:0000077 (Retinal capillary hemangioma, Renal cell carcinoma, Abnormality of the pancreas, Hemangioblastoma, 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: 11 (Father)

KindredID: 7

Case: M, 39Y0M, 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 24 presented with renal abnormalities, and pheochromocytoma, and died at age 62. ID 1 presented with pheochromocytoma. ID 2 presented with pancreatic abnormalities. ID 10 presented with CNS hemangioblastoma, pancreatic abnormalities and pheochromocytoma. ID 4 presented with pheochromocytoma.

CasePresentingHPOs: HP:0002666; HP:0000077; HP:0001732 (Pheochromocytoma, Abnormality of the kidney, Abnormality of the pancreas)

CaseHPOFreeText: The patient presented with renal and pancreatic cyst or tumor (unspecified) (33Y), pheochromocytoma (21Y) and other undefined phenotypes (33Y).

CaseNotHPOs: HP:0009711; HP:0005584; HP:0010797 (Retinal capillary hemangioma, Renal cell carcinoma, Hemangioblastoma)

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

GroupID: 29b

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL CohortInfo: a retrospective cohort study from an eye centre in Germany involved 148 VHL patients and their genetic data involved in retinal capillary hemangiomas.

CasePresentingHPOs: N/A

CaseHPOFreeText: This was 1 of 4 patients discussed with this mutation. The individual did NOT have retinal hemangiomas; Other VHL manifestations were discussed but not per- variant.

CaseNotHPOs: HP:0009711 (retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Yes - Supplementary Table S1

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: 194

KindredID: 194

Case: Sex Unknown, 46Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0010797; HP:0001732; HP:0002666; HP:0000107 (Hemangioblastoma, Abnormality of the pancreas, Pheochromocytoma, Renal cyst)

CaseHPOFreeText: CNS hemangioblastoma, pancreatic cyst or tumor, pheochromocytoma and renal cystic lesion.

CaseNotHPOs: HP:0009711; HP:0006770 (Retinal capillary hemangioma, Clear cell renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Table S1, S2 and S3

Variant: p.P59Rfs*8 (c.176del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA432536374, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.176del

gnomAD: N/A

VariantEvidence: N/A

MutationType: deletion; minus_1_frameshift_variant

CivicName: P59fs (c.176delC)

MultipleGeneVariants: N/A

PatientID: 7

KindredID: 7

Case: 55Y0M, Sex unknown, Chinese

DiseaseAssertion: VHL

FamilyInfo: Positive -- Their father and brother both had the same germline mutation. Their father was screened after genetic testing and found to have a left RCC with lung metastasis at age 80, and their brother was asymptomatic.

CasePresentingHPOs: HP:0010797 (hemangioblastoma)

CaseHPOFreeText: CNS hemangioblastoma first presenting at 55Y

CaseNotHPOs: HP:0005584; HP:0002666; HP:0009715 (renal cell carcinoma, pheochromocytoma, Papillary cystadenoma of the epididymis)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

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

CaseProblemVariantFreeText: N/A

LegacyVariant: 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