GroupID: 8

Case: 37Y0M, Sex Unknown, Ethnicity Unknown

DiseaseAssertion: assumed VHL

FamilyInfo: 1 of the 573 patients discussed in this paper were found to have this variant. This mutation was found in 1 VHL family with a single patient.

CasePresentingHPOs: HP:0005584; HP:0009711; HP:0006880 (renal cell carcinoma; retinal capillary hemangioma; cerebellar hemangioblastoma)

CaseHPOFreeText: patient had retinal angiomas diagnosed at 28Y, cerebellar hemangioblastomas diagnosed at 22Y, and renal cell carcinoma diagnosed at 37Y.

CaseNotHPOs: HP:0002666 (pheochromocytoma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Supplementary Table S1.

Variant: p.R177* (c.529A>T)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: 625258 https://www.ncbi.nlm.nih.gov/clinvar/variation/625258/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: stop_gained

CivicName: R177* (c.529A>T)

MultipleGeneVariants: N/A

PatientID: V1

KindredID: 1

Case: M, 24Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: This patient’s brother also had this germline mutation and at least one brainstem hemangioblastoma at 30 years old.

CasePresentingHPOs: HP:0006880 (Cerebellar hemangioblastoma)

CaseHPOFreeText: Study reports 2 cerebellar hemangioblastomas at the ages of 22 and 24. Other phenotype information not provided.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Table 2

Variant: p.Q73Rfs*86 (c.216del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA432536422, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA432536422

gnomAD: N/A

VariantEvidence: The c.216delC variant was not genetically confirmed to be germline but was found in tumor samples from both the siblings.

MutationType: minus_1_frameshift_variant

CivicName: S72fs (c.216delC)

MultipleGeneVariants: N/A

PatientID: IP (Proband)

KindredID: D

Case: F, 22Y0M, Hungarian

DiseaseAssertion: VHL

FamilyInfo: Index patient was a young woman who presented with cerebellar hemangioblastoma, multiple renal cysts, retinal detachment with vitreous hemorrhage, pancreatic cyst, spinal cord hemangiomas, and recurrence of the cerebellar lesion. Family members were not available for clinical and genetic screening, but family history revealed that the patient's father died of metastatic renal cell carcinoma.

CasePresentingHPOs: HP:0006880; HP:0005562; HP:0001737; HP:0000541; HP:0007902; HP:0009713 (Cerebellar hemangioblastoma, Multiple renal cysts, Pancreatic cysts, Retinal detachment, Vitreous hemorrhage, Spinal hemangioblastoma)

CaseHPOFreeText: Patient underwent surgery for cerebellar hemangioblastoma at the age of 22 years. Multiple renal cysts and retinal detachment with vitreous hemorrhage were also observed. At the age of 26 years, pancreatic cyst, spinal cord hemangiomas, and recurrence of the cerebellar lesion were found. Diagnosed with VHL Type 1.

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

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: Exon 2 Deletion (c.341-?_463+?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 Deletion

MultipleGeneVariants: N/A

Patient ID: B6

KindredID: 6

Case: F, 22Y0M, Ethnicity Unknown

DiseaseAssertion: cerebellar hemangioblastoma

FamilyInfo: No testing in family history

CasePresentingHPOs: HP:0006880 (cerebellar hemangioblastoma)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: no other clinical features were found after the cerebellar hemangioblastoma during 2 years and 7 month follow-up

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.C162Y (c.485G>A)

LegacyVariant: p.C162Y (c.698G>A)

ClinVarID: 223225 (https://www.ncbi.nlm.nih.gov/clinvar/variation/223225/)

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: C162Y(c.485G>A)

MultipleGeneVariants: N/A

PatientID: 11

KindredID: 11

Case: F, 36Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: There was said to be, at the time, no affected relatives

CohortInfo: An international consortium registered patients with head and neck paragangliomas with VHL or RET gene mutations.

CasePresentingHPOs: HP:0006748; HP:0002668; HP:0006476; HP:0006880; HP:0009711; HP:0000618; HP:0010797 (adrenal pheochorocytoma, paraganglioma, abnormality of the pancreatic islet cells, cerebellar hemangioblastoma, retinal capillary hemangioblastoma, blindness, hemangioblastoma)

CaseHPOFreeText: At 8Y, (in 1978), she was operated for a right pheochromocytoma; at age 13 for a contralateral pheochromocytoma; at age 15, for a 4-cm mass at the neck was diagnosed by selective arteriography as a carotid paraganglioma. The patient was then operated twice for cerebellar hemangioblastoma at age 22, leading to the diagnosis of VHL disease. At age 27, the patient was operated again for a retrocaval pheochromocytoma and for islet cell tumors. The patient was also repeatedly treated for bilateral retinal hemangioblastomas leading to blindness at age 32. At age 36, again a pheochromocytoma was removed

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.T157I (c.470C>T)

LegacyVariant: p.T157I

CaseProblemVariantFreeText: The publication only provides the p., the mutation was able to be deduced to p.T157I (c.470C>T)

ClinVarID: 223223 https://www.ncbi.nlm.nih.gov/clinvar/variation/223223/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: T157I (c.470C>T)

MultipleGeneVariants: N/A