PatientID: 230

KindredID: 86

Case: F, 40Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: The proband (patient 229) had a sister (patient 230) who was genetically confirmed with the mutation, and presented with a CNS hemangioblastoma at age 40. The proband's brother 1 (patient 231) was also confirmed with the mutation and had a retinal angioma at 25, and renal cell carcinoma at 54. The proband's brother 2 passed away before they could be diagnosed/ confirmed with the mutation, but they had a CNS hemangioblastoma at 35. Finally, the proband's nephew (son of brother 2) was genetically confirmed with the mutation and presented with renal cell carcinoma at age 30.

CasePresentingHPOs: HP:0010797 (Hemangioblastoma)

CaseHPOFreeText: The proband's sister (patient 230) had a CNS hemangioblastoma at age 40.

CaseNotHPOs: HP:0002666; HP:0001737; HP:0001732; HP:0005584; HP:0009711 (Pheochromocytoma, Pancreatic cysts, Abnormality of the pancreas, Renal cell carcinoma, Retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: This patient was also published in a later paper by Wang et al., 2018 (PMID: 29330336).

SupplementalData: Patient and family genotype-phenotype information is listed in Supplementary Table 1.

Variant: p.L178R (c.533T>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 625261, https://www.ncbi.nlm.nih.gov/clinvar/variation/625261/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: L178R (c.533T>G)

MultipleGeneVariants: N/A

PatientID: 12

KindredID: 12

Case: Sex Unknown, 42Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: Patient had no family history of VHL disease.

CohortInfo: 16 Chinese patients clinically diagnosed with VHL disease.

CasePresentingHPOs: HP:0010797; HP:0005584; HP:0001732 (hemangioblastoma; renal cell carcinoma; abnormality of the pancreas)

CaseHPOFreeText: The patient presented with a hemangioblastoma at age 36 and then renal cell carcinoma and multiple pancreatic cysts or tumors at age 40.

CaseNotHPOs: HP:0009711, HP:0002666, HP:0030393, HP:0030424 (retinal capillary hemangioma, pheochromocytoma, endolymphatic sac tumor, epididymal cyst)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.F76del (c.227-229delTCT)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA357012, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.224_226delTCT

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: F76del (c.224_226delTCT)

MultipleGeneVariants: N/A

PatientID: 8 (Mother)

KindredID: 3

Case: F, 43Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: 3 members of this family were genetically confirmed to be carriers of a germline partial deletion of exon 2 of the VHL gene. ID 2 presented with retinal angioma and pancreatic abnormality. ID 1 was asymptomatic. ID 16 presented with a retinal angioma (33Y), CNS hemangioblastoma at (32Y) and died at age 42. ID 16 was stated as having the germline variant but this was inferred from family/personal history and was not genetically confirmed.

CasePresentingHPOs: HP:0010797 (Hemangioblastoma)

CaseHPOFreeText: The patient presented with CNS hemangioblastoma (26Y and 40Y).

CaseNotHPOs: HP:0005584; HP:0001732; HP:0000077; HP:0002666; HP:0009711 (Renal cell carcinoma, Abnormality of the pancreas, Abnormality of the kidney, Pheochromocytoma, Retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table 1.

Variant: Exon 2 Partial Deletion

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: deletion

CivicName: Null (Partial deletion of Exon 2)

MultipleGeneVariants: N/A

PatientID: 27

KindredID: 9

Case: F, 40Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0001737; HP:0001732; HP:0005584; HP:0010797 (Pancreatic cysts, Abnormality of the pancreas, Renal cell carcinoma, Hemangioblastoma)

CaseHPOFreeText: The proband, patient 27, presented at age 36 with a CNS hemangioblastoma, and renal cell carcinoma and multiple pancreatic cysts and tumors at 40.

CaseNotHPOs: HP:0002666, HP:0009711 (Pheochromocytoma, Retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: This patient was also published in a later paper by Wang et al., 2018 (PMID: 29330336). This mutation was also published in PMID 32179488 in reference to one patient with VHL disease type 1 in this paper with the c.227_229del variant. However, it is unclear whether patient #27, #28, or #30 is specifically published in PMID 32179488.

SupplementalData: Patient and family genotype-phenotype information is listed in Supplementary Table 1.

Variant: p.F76del (c.227_229del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA357012; https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.224_226del

gnomAD: N/A

VariantEvidence: N/A

MutationType: inframe_deletion

CivicName: F76del (c.224_226delTCT)

MultipleGeneVariants: N/A

PatientID: 8

KindredID: 1 (group ID 5)

Case: M, 48Y0M, Chinese

DiseaseAssertion: assumed VHL

CohortInfo: Clinical characteristics of 258 patients from 80 unrelated Chinese families were reported in this study. Grouped by the 21 mutations found, 2 families with 21 members total were described, and phenotypic information was given for this group.

FamilyInfo: In family 1, 17 members were described. The first generation describes 5 members with the VHL mutation, each passing on the gene to further generations. Patient 8’s father and sister had this familial mutation. His one son had not been yet tested at the time of the study. See Fig 4 for family pedigree; Table 3 for details.

CasePresentingHPOs: HP:0010797 (hemangioblastoma)

CaseHPOFreeText: He had CNS hemangioblastomas at 40Y

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.W88R (c.262T>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 496053 https://www.ncbi.nlm.nih.gov/clinvar/variation/496053/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: W88R (c.262T>C)

MultipleGeneVariants: N/A