PatientID: 280

KindredID: 110

Case: M, 22Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: The proband, patient 280, presented with a CNS hemangioblastoma at age 16, a retinal angioma at age 15, and multiple pancreatic cysts/tumors at age 22. Their father presented with a CNS hemangioblastoma at age 25, and retinal angioma at age 29.

CasePresentingHPOs: HP:0010797; HP:0001737; HP:0001732; HP:0009711 (Hemangioblastoma, Pancreatic cysts, Abnormality of the pancreas, Retinal capillary hemangioma)

CaseHPOFreeText: The proband, patient 280, presented with a CNS hemangioblastoma at age 16, a retinal angioma at age 15, and multiple pancreatic cysts/tumors at age 22.

CaseNotHPOs: HP:0002666; HP:0005584 (Pheochromocytoma, Renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: This cohort 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: Exon 2-3 Deletion (c.341-?_642+?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 2-3 Deletion

MultipleGeneVariants: N/A

PatientID: I

KindredID: 18

Case: Sex Unknown, 48Y0M, Danish

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0001737; HP:0000112 (Pancreatic cysts, Nephropathy)

CaseHPOFreeText: Diagnosed with VHL at age 14Y. Presented with 3 pancreatic cysts (14Y) and kidney disease (16Y). Age at the end of study: 48Y.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Q203Tfs*53 (c.606dup)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 935385, https://www.ncbi.nlm.nih.gov/clinvar/variation/935385/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: duplication; plus_1_frameshift_variant

CivicName: Q203TfsX53 (c.606dupA)

MultipleGeneVariants: N/A

PatientID: III

KindredID: 17

Case: Sex Unknown, 26Y0M, Danish

DiseaseAssertion: VHL

FamilyInfo: 2 other family members were found to have this VHL variant. Patient 17-I was asymptomatic. Patient 17-II presented with CNS hemangioblastoma (8Y).

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

CaseHPOFreeText: Diagnosed with VHL at age 10Y. Presented with 6 pancreatic cysts (15Y) and retinal hemangioblastoma (16Y). Age at the end of study: 26Y.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: Exon 1 Deletion (c.1-?_340+?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 Deletion

MultipleGeneVariants: N/A

PatientID: DIII7

KindredID: D

Case: F, 16Y0M, Chinese

DiseaseAssertion: pancreatic cysts

FamilyInfo: A 3-generation family is given with 3 confirmed members with this mutation. 2 other members had VHL-presenations however had not been tested for the gene.

CasePresentingHPOs: HP:0001737 (pancreatic cysts)

CaseHPOFreeText: initially diagnosed by genetic analysis and further verified radiologically, to be found with pancreatic cysts at 16Y.

CaseNotHPOs: HP:0010797; HP:0002666; HP:0009711; HP:0005584 (hemangioblastoma, pheochromocytoma, retinal capillary hemangioma, renal cell carcinoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.F76del (c.226_228delTTC)

LegacyVariant: p.F76del (c.439delTCT)

CaseProblemVariantFreeText: NM_000551.3:c.226_228delTTC automaps to NM_000551.3:c.227_229delTCT

ClinVarID: N/A

CAID: CA357012 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.226_228delTTC

gnomAD: N/A

VariantEvidence: N/A

MutationType: inframe_deletion

CivicName: F76del (c.227_2289delTCT)

MultipleGeneVariants: N/A

PatientID: 2

KindredID: 2

Case: F, 29Y0M, Brazilian

DiseaseAssertion: VHL

FamilyInfo: VHL type 1. Genetic testing has been performed in her parents and brother with negative results. Her only child has not undergone predictive testing yet.

CasePresentingHPOs: HP:0030393; HP:0009711; HP:0010797; HP:0000107; HP:0001737; HP:0001407 (endolymphatic sac tumor; retinal capillary hemangioma; hemangioblastoma; renal cysts; pancreatic cysts; hepatic cysts)

CaseHPOFreeText: endolymphatic sac tumor diagnosed at 11Y, retinal angiomas at 16Y; hemangioblastoma, renal, pancreatic, and hepatic cysts at 29Y

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Yes

Variant: p.Q73* (c.217C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223164 https://www.ncbi.nlm.nih.gov/clinvar/variation/223164/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: stop_gained

CivicName: Q73* (c.217C>T)

MultipleGeneVariants: N/A