PatientID: II-1

KindredID: 1

Case: M, 57Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Family in India but Ethnicity not explicitly confirmed. Two children with the same mutation. Eldest son presented at age 10 with severe hypertension and bilateral pheochromocytoma. Daughter presented at age 17 with palpitation, blurred vision, blurring vision, bilateral papilledema and bilateral pheochromocytoma. Wife and brother were negative for the mutation.

CasePresentingHPOs: HP:0000822; HP:0002666; HP:0006748; HP:0002315; HP:0001250; HP:0031657 (Hypertension, Pheochromocytoma, Adrenal pheochromocytoma, Headache, Seizure, Abnormal heart sound)

CaseHPOFreeText: Presented at 14 years-old with severe hypertension. On evaluation he was found to have a right adrenal mass with elevated urinary VMA, confirming the diagnosis of a right adrenal pheochromocytoma. Presented at age 22 with severe headache and recurrent seizures. Cardiac auscultation revealed a loud 2nd heart sound and a 3rd heart sound. Examination of the abdomen revealed a palpable mass in the left hypochondrium. This mass was confirmed as a pheochromocytoma. Asymptomatic at age 57.

CaseNotHPOs: HP:0030148 (Heart murmur)

CaseNotHPOFreeText: There were no heart murmurs during evaluation at age 22.

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Figure 1

Variant: p.R82L (c.245G>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 526675, https://www.ncbi.nlm.nih.gov/clinvar/variation/526675/

CAID: N/A

gnomAD: N/A

VariantEvidence: Authors carried out analysis of VHL variant p.Arg82Leu with six different in silico tools namely SIFT, I-Mutant3, PhD-SNP, MutPred, PolyPhen2 and SNPs&GO in order to determine the pathogenic potential of the variant.

MutationType: missense_variant;transversion

CivicName: R82L (c.245G>T)

MultipleGeneVariants: N/A

PatientID: N/A (case)

KindredID: 1

Case: F, 45Y0M, Italian

DiseaseAssertion: Assumed VHL

FamilyInfo: Genetic analysis was performed on the patients relatives, including her daughter. Her 55Y0M brother had the same mutation but no clinical signs of VHL disease.

CasePresentingHPOs: HP:0006748; HP:0030405 (adrenal pheochromocytoma, pancreatic neuroendocrine tumour)

CaseHPOFreeText: At 22Y0M, she had surgery for a right adrenal pheochromocytoma. Two years later, a pancreatic oduodenectomy was performed to remove a pancreatic neuroendocrine tumor. 21 years later, abdominal lymph node metastases of the pancreatic neuroendocrine that was removed 21 years prior had occurred. Three abdominal nodules that were found to be neuroendocrine tumours immunohistochemical characteristics were removed. The patient’s clinical history suggested a hereditary endocrine syndrome.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

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

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

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