PatientID: II-4

KindredID: 1

Case: M, Age Unknown (deceased), Ethnicity Unknown

DiseaseAssertion: hemangioblastoma

FamilyInfo: His family members had features apparently related to VHL disease. His mother was troubled with severe headache during her lifetime, though the cause of death was unclear. His son was diagnosed with brain hemangioblastoma, and his daughter had various VHL phenotypes. His daughter and son were tested with the same mutation, and so it was assumed that he did too

CasePresentingHPOs: HP:0010797 (hemangioblastoma)

CaseHPOFreeText: He had diabetes mellitus requiring insulin therapy, underwent brain surgery twice and was diagnosed with brain hemangioblastoma, which was his cause of death

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Y98Tfs*61 (c.291delC) [assumed]

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA432420512 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.291delC

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: Y98fs (c.291delC)

MultipleGeneVariants: N/A

PatientID: 14

KindredID: N/A

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CohortInfo: The authors evaluated 64 VHL patients (32 women and 32 men) with renal involvement of whom 54/64 had undergone renal surgery or a radiofrequency thermal ablation procedure for RCC. In 10/64 VHL patients, at least one or more RCC were diagnosed, however at the time of diagnosis an indication for treatment was not yet present. For all patients several CT/MRI scans existed for retrospective description of tumour growth kinetics.

CasePresentingHPOs: HP:0005584 (Renal cell carcinoma)

CaseHPOFreeText: This is a tumor resolution study (VHL patients were investigated based on the presence of renal tumors.) No other phenotypic information is available.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table S1 describes 19 patients with missense mutations, including this patient.

Variant: p.P154L (c.461C>T)

LegacyVariant: c.674C>T

CaseProblemVariantFreeText: N/A

ClinVarID: 649525, https://www.ncbi.nlm.nih.gov/clinvar/variation/649525/?new_evidence=true

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: P154L (c.461C>T)

MultipleGeneVariants: N/A

GroupID/ KindredID: 49CA

DiseaseAssertion: VHL

GroupSize: N/A

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: This germline familial VHL mutation was taken from the Cambridge, Department of Pathology database, with an unknown number of members belonging to Family ID 49CA. Table 4 lists all ID and mutations associated with individuals with pheochromocytoma.

GroupPresentingHPOs: HP:0002666 (pheochromocytoma)

GroupHPOFreeText: Described as a VHL family with pheochromocytoma. Other phenotypes are likely, including renal cell carcinoma, however not detailed here.

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.P154L (c.461C>T)

LegacyVariant: p.P154L (c.674C>T)

CaseProblemVariantFreeText: N/A

ClinVarID: 649525 https://www.ncbi.nlm.nih.gov/clinvar/variation/649525/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: P154L (c.461C>T)

MultipleGeneVariants: N/A

PatientID: BII:6

KindredID: B

Case: M, 24Y0M (deceased), Chinese

DiseaseAssertion: cerebellar hemangioblastoma

FamilyInfo: A 3-generation family is given with 1 confirmed member tested for VHL (proband: III:5). His mother likely had the mutation as the mother and her brother both had VHL phenotypes at young ages (27Y and 22Y).

CasePresentingHPOs: HP:0006880 (cerebellar hemangioblastoma)

CaseHPOFreeText: Patient had operation for cerebellar hemangioblastoma at the age of 22 and died of bilateral multiple hemangioblastoma at the age of 24, with no chance of surgical treatment.

CaseNotHPOs: HP:0009711; HP:0002666; HP:0005584; HP:0001737 (retinal capillary hemangioma, pheochromocytoma, renal cell carcinoma, pancreatic cysts)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.P154L (c.461C>T) [assumed]

LegacyVariant: p.P154L (c.647C>T)

CaseProblemVariantFreeText: N/A

ClinVarID: 649525, https://www.ncbi.nlm.nih.gov/clinvar/variation/649525/

CAID: N/A

gnomAD: N/A

VariantEvidence: No genetic testing was done prior to death, however family history and presentation leads to this assumption

MutationType: missense_variant; transition

CivicName: P154L (c.461C>T)

MultipleGeneVariants: N/A

PatientID: 49

KindredID: 49

Case: Sex Unknown, Age Unknown, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CasePresentingHPOs: HP:0100634 (Neuroendocrine neoplasm)

CaseHPOFreeText: Recorded as a pheochromocytoma/paraganglioma

CaseNotHPOs: HP:0010797; HP:0006770; HP:0030405; HP:0009711; HP:0030421 (hemangioblastoma; clear cell renal cell carcinoma; 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: p.P154L (c.461C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 649525 https://www.ncbi.nlm.nih.gov/clinvar/variation/649525/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: P154L (c.461C>T)

MultipleGeneVariants: N/A