PatientID: 43

KindredID: F01

Case: M, Age Unknown, Unknown Ethnicity

DiseaseAssertion: VHL

FamilyInfo: A total of 12 members of this family (F01) had a complete deletion of the VHL gene. Five of these patients (16, 18, 21, 33, 43) presented with clinical features of VHL. This family was previously published except for patients 43 and 48 which were newly diagnosed with VHL disease in the current study.

CasePresentingHPOs: HP:0010797 (Hemangioblastoma)

CaseHPOFreeText: CNS hemangioblastoma.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 17537157

SupplementalData: Figure 2.

Variant: Complete Deletion

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: Deletion of ~250.9kb resulted in deletion of the VHL gene.

MutationType: deletion

CivicName: Deletion

MultipleGeneVariants: N/A

PatientID: 21

KindredID: F01

Case: F, Age Unknown, Unknown Ethnicity

DiseaseAssertion: VHL

FamilyInfo: A total of 12 members of this family (F01) had a complete deletion of the VHL gene. Five of these patients (16, 18, 21, 33, 43) presented with clinical features of VHL. This family was previously published except for patients 43 and 48 which were newly diagnosed with VHL disease in the current study.

CasePresentingHPOs: HP:0010797 (Hemangioblastoma)

CaseHPOFreeText: CNS hemangioblastoma.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 17537157

SupplementalData: Figure 2.

Variant: Complete Deletion

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: Deletion of ~250.9kb resulted in deletion of the VHL gene.

MutationType: deletion

CivicName: Deletion

MultipleGeneVariants: N/A

PatientID: 38

KindredID: F01

Case: M, Age Unknown, Unknown Ethnicity

DiseaseAssertion: Asymptomatic

FamilyInfo: A total of 12 members of this family (F01) had a complete deletion of the VHL gene. Five of these patients (16, 18, 21, 33, 43) presented with clinical features of VHL. This family was previously published except for patients 43 and 48 which were newly diagnosed with VHL disease in the current study.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 17537157

SupplementalData: Figure 2.

Variant: Complete Deletion

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: Deletion of ~250.9kb resulted in deletion of the VHL gene.

MutationType: deletion

CivicName: Deletion

MultipleGeneVariants: N/A

PatientID: 18

KindredID: F01

Case: M, Age Unknown, Unknown Ethnicity

DiseaseAssertion: VHL

FamilyInfo: A total of 12 members of this family (F01) had a complete deletion of the VHL gene. Five of these patients (16, 18, 21, 33, 43) presented with clinical features of VHL. This family was previously published except for patients 43 and 48 which were newly diagnosed with VHL disease in the current study.

CasePresentingHPOs: HP:0010797; HP:0001737 (Hemangioblastoma, Pancreatic cysts)

CaseHPOFreeText: CNS hemangioblastoma and pancreatic cyst.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 17537157

SupplementalData: Figure 2.

Variant: Complete Deletion

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: Deletion of ~250.9kb resulted in deletion of the VHL gene.

MutationType: deletion

CivicName: Deletion

MultipleGeneVariants: N/A

PatientID: 31

KindredID: F01

Case: M, Age Unknown, Taiwanese

DiseaseAssertion: Asymptomatic

FamilyInfo: A total of 10 members of this family (F01) had a complete deletion of the VHL gene. Four of these patients (16, 18, 21, 33) presented with clinical features of VHL.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 19288063

SupplementalData: Figure 1

Variant: Complete Deletion

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: Deletion of 142.9kb resulted in deletion of the VHL gene.

MutationType: deletion

CivicName: Deletion

MultipleGeneVariants: N/A

PatientID: 28

KindredID: F01

Case: F, Age Unknown, Taiwanese

DiseaseAssertion: Asymptomatic

FamilyInfo: A total of 10 members of this family (F01) had a complete deletion of the VHL gene. Four of these patients (16, 18, 21, 33) presented with clinical features of VHL.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 19288063

SupplementalData: Figure 1

Variant: Complete Deletion

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: Deletion of 142.9kb resulted in deletion of the VHL gene.

MutationType: deletion

CivicName: Deletion

MultipleGeneVariants: N/A

PatientID: 30

KindredID: PM

Case: M, 49Y0M, Indian

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0010797; HP:0001737 (Hemangioblastoma, Pancreatic cysts)

CaseHPOFreeText: CNS hemangioblastoma and multi-cystic pancreatic lesions.

CaseNotHPOs: HP:0030393; HP:0009711; HP:0002666; HP:0005584 (Endolymphatic sac tumor, Retinal capillary hemangioma, Pheochromocytoma, Renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: Complete Deletion

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: This variant is noted as a full-length deletion involving genes BRK1 and FANCD2.

MutationType: deletion

CivicName: Deletion

MultipleGeneVariants: N/A

27 index patients suspected of having VHL disease from unrelated Chinese families and their relatives were studied. The nucleotide were numbered according to the sequence numbering by Latif et al, 1993 and this was converted to NM_000551.3. The paper did not differentiate between a pancreatic cysts and tumor and presented these together as a 'pancreatic lesion'. The paper summarized the phenotypes of the families together. Family 21 and 25 were each one member (proband) each and were found with complete VHL deletions. Proband 21 had only hemangioblastoma and genetic testing of her parents confirmed a de novo mutation. Proband 25 was found with hemangioblastoma, retinal angioma and pancreatic lesion. Proband 25 had no family history of VHL but parents were not available for genetic testing so de novo mutation cannot be assessed. ACMG PVS1

PatientID: 74

KindredID: 74 *

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: * 3 patients (IDs: 74, 75, 76) were previously reported in Aronoff et al, 2018 as family 13.

CasePresentingHPOs: HP:0010797 (hemangioblastoma)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0006770; HP:0100634; HP:0030405; HP:0009711; HP:0030421 (clear cell renal cell carcinoma; Neuroendocrine neoplasm, pancreatic neuroendocrine neoplasm, retinal capillary hemangioma, Epididymal neoplasm)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 29437867

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

Variant: complete deletion

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: deletion

CivicName: Deletion

MultipleGeneVariants: N/A

PatientID: 76

KindredID: 76 *

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL (asymptomatic)

FamilyInfo: * 3 patients (IDs: 74, 75, 76) were previously reported in Aronoff et al, 2018 as family 13.

CasePresentingHPOs: None

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0010797; HP:0006770; HP:0100634; HP:0030405; HP:0009711; HP:0030421 (hemangioblastoma; clear cell renal cell carcinoma; Neuroendocrine neoplasm, pancreatic neuroendocrine neoplasm, retinal capillary hemangioma, Epididymal neoplasm)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 29437867

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

Variant: complete deletion

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: deletion

CivicName: Deletion

MultipleGeneVariants: N/A

PatientID: None

KindredID: VHL24

Case: M, 22Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CohortInfo: A total of 190 patients recruited by the COMETE network over 15 years were included in the study.

CasePresentingHPOs: HP:0002666 (Pheochromocytoma)

CaseHPOFreeText: The patient had one benign pheochromocytoma.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET/SDHB/SDHC/SDHD

PreviouslyPublished: N/A

SupplementalData: Table 1 of Supplementary

Variant: Complete Deletion (c.1-?_642+?del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: The patient had no LOH found in the BAC array CGH data. Somatic VHL variant c.250G>C was found in the tumor tissue.

MutationType: deletion

CivicName: Deletion

MultipleGeneVariants: N/A

GroupID/ KindredID: 7

DiseaseAssertion: VHL

GroupSize: Unknown

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: Brazilian

GroupAgeRange: N/A

GroupInfo: Family VHL type 1 - did not exhibit any renal lesions - unclear how many members were involved

GroupPresentingHPOs: N/A

GroupHPOFreeText: N/A

GroupNotHPOs: N/A

GroupNotHPOFreeText: No renal lesions

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Yes

Variant: VHL partial deletion

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: deletion also encompassed the FANCD2 gene and predictably the neighbouring C3orf10 gene

MutationType: deletion

CivicName: Deletion

MultipleGeneVariants: N/A

PatientID: A (Tumor 2)

KindredID: 1

Case: F, 57Y0M, Ethnicity Unknown

DiseaseAssertion: assumed VHL

FamilyInfo: This kindred with a VHL germline deletion was studied. Apparently inherited from her father and paternal grandmother as they were affected, and passed to daughter but no phenotypic data was provided for these familials. Her sister and nephew also presented with hemangioblastomas and this germline deletion, and further somatic details were studied.

CasePresentingHPOs: HP:0006880 (cerebellar hemangioblastoma)

CaseHPOFreeText: 2 cerebellar HB surgically resected at 57Y and found with somatic mutations in both tumors

CaseNotHPOs: N/A

CaseNotHPOFreeText: no VHL-associated visceral malignancies in the patient

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.K159E (c.475A>G)

LegacyVariant: c.8678 (p.Lys159Glu)

CaseProblemVariantFreeText: A somatic mutation in exon 3 (nt: c.8678 (p.Lys159Glu)) via Latif et al.’s (1993) old transcript) was used.

ClinVarID: 825149 https://www.ncbi.nlm.nih.gov/clinvar/variation/825149/

CAID: N/A

gnomAD: N/A

VariantEvidence: unspecified germline deletion as demonstrated by FISH analysis. “Second-hit” tumorigenesis displayed due to somatic mutation found, which was not predicted by the specific germline deletion nor by the overall genetic composition of the patient. Both of this patient’s cerebellar tumors had somatic mutations.

MutationType: missense_variant; transition

CivicName: Deletion

MultipleGeneVariants: Germline, VHL, deletion; Somatic, VHL, c.903_904insT (p.*151)

GroupID/ KindredID: 28

PatientID: IV

Case: 62Y0M, Sex unknown, Polish

DiseaseAssertion: VHL

FamilyInfo: Family 28 consisted of 4 members; one relative (age 27Y) was found with multiple cerebellar HABs at 25Y, and multiple spinal HABs, another was diagnosed with a single cerebellar HAB at 24Y, and a final relative (40Y), was diagnosed at 30Y with multiple cerebellar HABs, and multiple spinal HABs

CasePresentingHPOs: HP:0006880 (cerebellar hemangioblastoma)

CaseHPOFreeText: Patient was diagnosed with a single HAB at 62Y.

GroupNotHPOs: HP:0009713; HP:0009711; HP:0005584 (spinal hemangioblastoma, retinal capillary hemangioma; renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: complete deletion of VHL gene

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: Haplotype analysis information in Table 3

MutationType: deletion

CivicName: deletion

MultipleGeneVariants: N/A

GroupID/ KindredID: 28

PatientID: III

Case: 40Y0M, Sex unknown, Polish

DiseaseAssertion: VHL

FamilyInfo: Family 28 consisted of 4 members; one relative (age 27Y) was found with multiple cerebellar HABs at 25Y, and multiple spinal HABs, another was diagnosed with a single cerebellar HAB at 24Y, and a final relative (62Y), diagnosed with a single HAB.

CasePresentingHPOs: HP:0009713; HP:0006880 (spinal hemangioblastoma, cerebellar hemangioblastoma)

CaseHPOFreeText: Patient was diagnosed at 30Y with multiple cerebellar HABs, and multiple spinal HABs

GroupNotHPOs: HP:0009711; HP:0005584 (retinal capillary hemangioma; renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: complete deletion of VHL gene

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: Haplotype analysis information in Table 3

MutationType: deletion

CivicName: deletion

MultipleGeneVariants: N/A

GroupID/ KindredID: 28

PatientID: I

Case: 27Y0M, Sex unknown, Polish

DiseaseAssertion: VHL

FamilyInfo: Family 28 consisted of 4 members; one relative (age 24Y) diagnosed with a single cerebellar HAB, another (40Y) diagnosed at 30Y with multiple cerebellar HABs, and multiple spinal HABs, and a final relative (62Y), diagnosed with a single HAB.

CasePresentingHPOs: HP:0009713; HP:0006880 (spinal hemangioblastoma, cerebellar hemangioblastoma)

CaseHPOFreeText: Patient was found with multiple cerebellar HABs at 25Y, and multiple spinal HABs

GroupNotHPOs: HP:0009711; HP:0005584 (retinal capillary hemangioma; renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: complete deletion of VHL gene

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: Haplotype analysis information in Table 3

MutationType: deletion

CivicName: deletion

MultipleGeneVariants: N/A

GroupID/ KindredID: 28

PatientID: II

Case: 24Y0M, Sex unknown, Polish

DiseaseAssertion: VHL

FamilyInfo: Family 28 consisted of 4 members; one relative (age 27Y) was found with multiple cerebellar HABs at 25Y, and multiple spinal HABs, another (40Y) diagnosed at 30Y with multiple cerebellar HABs, and multiple spinal HABs, and a final relative (62Y), diagnosed with a single HAB.

CasePresentingHPOs: HP:0006880 (cerebellar hemangioblastoma)

CaseHPOFreeText: Patient was diagnosed with a single cerebellar HAB at 24Y

GroupNotHPOs: HP:0009713; HP:0009711; HP:0005584 (spinal hemangioblastoma, retinal capillary hemangioma; renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: complete deletion of VHL gene

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: Haplotype analysis information in Table 3

MutationType: deletion

CivicName: deletion

MultipleGeneVariants: N/A

PatientID: 29

KindredID: PM

Case: F, 35Y0M, Indian

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0001737 (Pancreatic cysts)

CaseHPOFreeText: Multi-cystic pancreatic lesions.

CaseNotHPOs: HP:0010797; HP:0030393; HP:0009711; HP:0002666; HP:0005584 (Hemangioblastoma, Endolymphatic sac tumor, Retinal capillary hemangioma, Pheochromocytoma, Renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: Complete Deletion

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: This variant is noted as a full-length deletion involving genes BRK1 and FANCD2.

MutationType: deletion

CivicName: Deletion

MultipleGeneVariants: N/A

PatientID: 28

KindredID: PM

Case: F, 31Y0M, Indian

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0010797; HP:0001737 (Hemangioblastoma, Pancreatic cysts)

CaseHPOFreeText: CNS hemangioblastoma and multi-cystic pancreatic lesions.

CaseNotHPOs: HP:0030393; HP:0009711; HP:0002666; HP:0005584 (Endolymphatic sac tumor, Retinal capillary hemangioma, Pheochromocytoma, Renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: Complete Deletion

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: This variant is noted as a full-length deletion involving genes BRK1 and FANCD2.

MutationType: deletion

CivicName: Deletion

MultipleGeneVariants: N/A

PatientID: 74

KindredID: 74

Case: Sex Unknown, 31Y0M, Ethnicity Unknown

DiseaseAssertion: Assumed VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0002666 (Pheochromocytoma)

CaseHPOFreeText: Single benign PCC.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Patient information pulled from Supplemental Table 1a.

Variant: Complete Deletion (c.1-?_642+?del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: Carbonic anhydrase 9 (CA9) mRNA level of 34.31 was detected. Membrane CA9 immunostaining was observed.

MutationType: deletion

CivicName: Deletion

MultipleGeneVariants: N/A

PatientID: 78

KindredID: 78

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL (asymptomatic)

FamilyInfo: N/A

CasePresentingHPOs: None

CaseHPOFreeText: N/A

CaseNotHPOs:HP:0010797; HP:0006770; HP:0100634; HP:0030405; HP:0009711; HP:0030421 (hemangioblastoma; clear cell renal cell carcinoma; Neuroendocrine neoplasm, pancreatic neuroendocrine neoplasm, retinal capillary hemangioma, Epididymal neoplasm)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

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

Variant: Deletion of 3p25.3

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: deletion

CivicName: Deletion

MultipleGeneVariants: N/A

PatientID: 37

KindredID: F01

Case: F, Age Unknown, Unknown Ethnicity

DiseaseAssertion: Asymptomatic

FamilyInfo: A total of 12 members of this family (F01) had a complete deletion of the VHL gene. Five of these patients (16, 18, 21, 33, 43) presented with clinical features of VHL. This family was previously published except for patients 43 and 48 which were newly diagnosed with VHL disease in the current study.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 17537157

SupplementalData: Figure 2.

Variant: Complete Deletion

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: Deletion of ~250.9kb resulted in deletion of the VHL gene.

MutationType: deletion

CivicName: Deletion

MultipleGeneVariants: N/A

PatientID: 16

KindredID: F01

Case: F, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: A total of 12 members of this family (F01) had a complete deletion of the VHL gene. Five of these patients (16, 18, 21, 33, 43) presented with clinical features of VHL. This family was previously published except for patients 43 and 48 which were newly diagnosed with VHL disease in the current study.

CasePresentingHPOs: HP:0010797 (Hemangioblastoma)

CaseHPOFreeText: CNS hemangioblastoma.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 17537157

SupplementalData: Figure 2.

Variant: Complete Deletion

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: Deletion of ~250.9kb resulted in deletion of the VHL gene.

MutationType: deletion

CivicName: Deletion

MultipleGeneVariants: N/A

PatientID: 32

KindredID: F01

Case: M, Age Unknown, Unknown Ethnicity

DiseaseAssertion: Asymptomatic

FamilyInfo: A total of 12 members of this family (F01) had a complete deletion of the VHL gene. Five of these patients (16, 18, 21, 33, 43) presented with clinical features of VHL. This family was previously published except for patients 43 and 48 which were newly diagnosed with VHL disease in the current study.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 17537157

SupplementalData: Figure 2.

Variant: Complete Deletion

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: Deletion of ~250.9kb resulted in deletion of the VHL gene.

MutationType: deletion

CivicName: Deletion

MultipleGeneVariants: N/A

PatientID: 19

KindredID: F01

Case: F, Age Unknown, Taiwanese

DiseaseAssertion: Asymptomatic

FamilyInfo: A total of 10 members of this family (F01) had a complete deletion of the VHL gene. Four of these patients (16, 18, 21, 33) presented with clinical features of VHL.

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 19288063

SupplementalData: Figure 1

Variant: Complete Deletion

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: Deletion of 142.9kb resulted in deletion of the VHL gene.

MutationType: deletion

CivicName: Deletion

MultipleGeneVariants: N/A

PatientID: 2

KindredID: 2

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: Hemangioblastoma

FamilyInfo: None

CasePresentingHPOs: HP:0010797 (Hemangioblastoma)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: deletion (deletion on chromosome 3 (>35kb, <90kb) resulting in complete loss of VHL gene)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: germline deletion on chromosome 3 (>35kb, <90kb) resulting in complete loss of VHL gene. Hemangioblastoma from this patient shows a missense mutation R200W(c.598C>T) in the second copy of VHL gene.

MutationType: deletion

CivicName: Deletion AND R200W (c.598C>T)

MultipleGeneVariants: Somatic, VHL, c.598C>T (p.Arg200Trp)

PatientID: 2

KindredID: 2

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: hemangioblastoma

FamilyInfo: N/A - Not specified

CasePresentingHPOs: HP:0010797 (hemangioblastoma)

CaseHPOFreeText: VHL syndromic HB

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: Null (Complete deletion)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: A VHL subject in our patient population had a full length deletion (FLD) in the germline VHL gene, but a VHL gene tumor second hit mutation (c.360-362 del AGA) causing an amino acid change of p.RD120-121S detected in the HB tumor

MutationType: deletion

CivicName: Deletion AND R120_121S (c.360_362delAGA)

MultipleGeneVariants: Somatic, VHL, c.360_362delAGA, p.Arg120_121Ser

PatientID: 24

KindredID: 24

Case: 17Y0M, sex unknown, ethnicity unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0009711 (retinal capillary hemangioma)

CaseHPOFreeText: See Table 1&2 for retinal capillary hemangioma information

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: Null (Complete deletion)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: Stated in paper as “del VHL”; complete vhl gene deletion

MutationType: deletion (exon_loss_variant)

CivicName: DELETION

MultipleGeneVariants: N/A

PatientID: 19

KindredID: 19

Case: 43Y0M, sex unknown, ethnicity unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0010797; HP:0005584; HP:0030405; HP:0009711 (hemangioblastoma; renal cell carcinoma; pancreatic endocrine tumor; retinal capillary hemangioma)

CaseHPOFreeText: See Table 1&2 for retinal capillary hemangioma information

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: Null (Complete deletion)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: Stated in paper as “del VHL”; complete vhl gene deletion

MutationType: deletion (exon_loss_variant)

CivicName: DELETION

MultipleGeneVariants: N/A

GroupID/ KindredID: 28

PatientID: II

Case: 24Y0M, Sex unknown, Polish

DiseaseAssertion: VHL

FamilyInfo: Family 28 consisted of 4 members; one relative (age 27Y) was found with multiple cerebellar HABs at 25Y, and multiple spinal HABs, another (40Y) diagnosed at 30Y with multiple cerebellar HABs, and multiple spinal HABs, and a final relative (62Y), diagnosed with a single HAB.

CasePresentingHPOs: HP:0006880 (cerebellar hemangioblastoma)

CaseHPOFreeText: Patient was diagnosed with a single cerebellar HAB at 24Y

GroupNotHPOs: HP:0009713; HP:0009711; HP:0005584 (spinal hemangioblastoma, retinal capillary hemangioma; renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: complete deletion of VHL gene

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: Haplotype analysis information in Table 3

MutationType: deletion

CivicName: deletion

MultipleGeneVariants: N/A