PatientID: None

KindredID: 1

Case: M, 48Y0M, Ethnicity Unknown

DiseaseAssertion: Assumed VHL

FamilyInfo: The patient’s daughter had bilateral adrenal pheochromocytoma at 27Y, and was found to have bilateral small lesions suspicious for inactive retinal angiomas upon further investigation. Genetic testing found that the patient’s daughter carried the same NM_000551.3:c.277G>A mutation that the patient was found to carry. The patient’s granddaughter was also found to carry the mutation. The patient's mother had also died at 42Y as a result of a stroke, and the patient’s uncle had died at 57Y as a result of a stroke. There is no genetic information available about them. The other daughter of the patient did not carry the mutation.

CasePresentingHPOs: HP:0006748; HP:0030424; HP:0000107 (Adrenal pheochromocytoma, epididymal cyst, renal cyst)

CaseHPOFreeText: The 48Y male patient presented with a right adrenal pheochromocytoma at 48Y. Further investigation revealed left epididymal cysts and bilateral renal cysts.

CaseNotHPOs: HP:0009713; HP:0009711 (Spinal hemangioblastoma, retinal hemangioblastoma)

CaseNotHPOFreeText: An MRI of the brain and spinal cord showed no signs of hemangioblastomas and examination of the eyes showed no retinal hemangioblastomas.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.G93S (c.277G>A)

LegacyVariant: N/A

ClinVarID: 2237, https://www.ncbi.nlm.nih.gov/clinvar/variation/2237/

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: G93S(c.277G>A)

MultipleGeneVariants: N/A

GroupID/ KindredID: 62CE, 4873NCI

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 multiple databases, including: the Munich, university of Freiburg and Institute of Pathology database, and the National Cancer Institute database, with an unknown number of members belonging to two family IDs: Family ID 62CE and 4873NCI. Table 4 lists all ID and mutations associated with individuals with pheochromocytoma.

GroupPresentingHPOs: HP:0002666 (pheochromocytoma)

GroupHPOFreeText: Described as 2 VHL families 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.G93S (c.277G>A)

LegacyVariant: p.G93S (c.490G>A)

CaseProblemVariantFreeText: N/A

ClinVarID: 2237 https://www.ncbi.nlm.nih.gov/clinvar/variation/2237/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transition

CivicName: G93S (c.277G>A)

MultipleGeneVariants: N/A

PatientID: None

KindredID: 5

Case: Sex Unknown, 60Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CohortInfo: All VHL mutation carriers of 18 years or older who underwent surveillance according to Dutch VHL guidelines between 1972 and 2012 in the VHL expertise centers University Medical Center Groningen (UMCG) and University Medical Center Utrecht (UMCU) were included. Patients with VHL-disease subtype 2C (pheochromocytoma only) were excluded.

CasePresentingHPOs: HP:0009711; HP:0009713; HP:0000107; HP:0002666; HP:0001737 (Retinal capillary hemangioma, Spinal hemangioblastoma, Renal cyst, Pheochromocytoma, Pancreatic cysts)

CaseHPOFreeText: VHL Type 2a/b.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: 24132471

SupplementalData: Table 1

Variant: p.G93S (c.277G>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 2237, https://www.ncbi.nlm.nih.gov/clinvar/variation/2237/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: G93S (c.277G>A)

MultipleGeneVariants: N/A