PatientID: 136

KindredID: 51

Case: M, 25Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: The proband (patient 136) has a mother (patient 137) who presented with a CNS hemangioblastoma at 32, and renal cell carcinoma/ pheochromocytoma at 38. However, no DNA sample was available for his mother's genetic testing.

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

CaseHPOFreeText: The proband (patient 136) presented with multiple pancreatic cysts/tumors at 21, renal cell carcinoma at 23, and a CNS hemangioblastoma at 25.

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).

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

Variant: p.P146Gfs*14 (c.435_436ins)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA2573131810, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2573131810

gnomAD: N/A

VariantEvidence: N/A

MutationType: plus_2_frameshift_variant

CivicName: P146Gfs*14 (c.435_436insGG)

MultipleGeneVariants: N/A

PatientID: 288

KindredID: 113

Case: M, 24Y0M, Chinese

DiseaseAssertion: VHL

FamilyInfo: The proband (patient 288) presented with a CNS hemangioblastoma, renal cell carcinoma, and multiple pancreatic cysts/tumors at 23, and a retinal angioma at 24. Their sister (patient 289) presented with a CNS hemangioblastoma, retinal angioma, and renal cell carcinoma at 30.

CasePresentingHPOs: HP:0010797; HP:0001732; HP:0001737; HP:0005584; HP:0009711 (Hemangioblastoma, Abnormality of the pancreas, Pancreatic cysts, Renal cell carcinoma, Retinal capillary hemangioma)

CaseHPOFreeText: The proband (patient 288) presented with a CNS hemangioblastoma, renal cell carcinoma, and multiple pancreatic cysts/tumors at 23, and a retinal angioma at 24.

CaseNotHPOs: HP:0002666 (Pheochromocytoma)

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 3 Deletion (c.464-?_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 3 Deletion

MultipleGeneVariants: N/A

PatientID: 1

KindredID: 5

Case: F, 13Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Positive. The patient's mother (4) also carried this mutation and had a hemangioblastoma. The proband's aunt (5) was confirmed to have the mutation and had VHL presentations. The cousin (8) had the mutation but was asymptomatic. The grandfather (13) was inferred to have the mutation and had a hemangioblastoma. See Figure 2a for family pedigree.

CohortInfo: 20 unrelated VHL families from an ethnically diverse cohort containing both affected and unaffected individuals.

CasePresentingHPOs: HP:0010797, HP:0001732 (hemangioblastoma, abnormality of the pancreas)

CaseHPOFreeText: The patient presented with a hemangioblastoma and abnormality of the pancreas at age 10.

CaseNotHPOs: HP:0009711, HP:0005584, HP:0002666, HP:0000077 (retinal capillary hemangioma, renal cell carcinoma, pheochromocytoma, abnormality of the kidney)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 31368132

SupplementalData: Supplementary file 1.

Variant: p.F136Lfs*23 (c.408delT)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 43601 https://www.ncbi.nlm.nih.gov/clinvar/variation/43601/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: F136Lfs*23 (c.408delT)

MultipleGeneVariants: N/A