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: N/A (daughter)

KindredID: 1

Case: F, 5Y0M, Ethnicity Unknown

DiseaseAssertion: asymptomatic

FamilyInfo: Her mother tested positive for the mutation: Q164R (c.491A<G), presenting with pheochromocytoma. Her cousin (26Y) had an adrenaland pancreatic tumors neuroendocrine carcinoma of uncertain origin, although no genetic testing.

CasePresentingHPOs: N/A

CaseHPOFreeText: asymptomatic likely due to young age

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Q164R (c.491A>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 2238 https://www.ncbi.nlm.nih.gov/clinvar/variation/2238/

CAID: N/A

gnomAD: N/A

VariantEvidence: To date, this germline VHL mutation was said to have been described in only 3 cases, with variable phenotypes, and in 2 cases PHEO occurred at a very young age.

MutationType: missense_variant;transition

CivicName: N/A

MultipleGeneVariants: N/A

PatientID: 1 (case)

KindredID: 1

Case: F, 37Y0M, Ethnicity Unknown

DiseaseAssertion: adrenal pheochromocytoma

FamilyInfo: Her one sister had died just after delivery, following a severe hypertensive crisis. Her 26-year-old niece presented with a 3 cm left adrenal tumor, an 8 cm pancreatic tumor and disseminated hepatic metastasis, evolving to death within a few months. Her liver biopsy was compatible with a moderately differentiated neuroendocrine carcinoma of uncertain origin. Molecular diagnosis was not performed in the affected sister and niece. Her asymptomatic 5Y old daughter tested positive for the mutation: Q164R (c.491A<G).

CasePresentingHPOs: HP:0006748 (adrenal pheochromocytoma)

CaseHPOFreeText: She first presented with paroxisms of severe hypertension associated with headaches, diaphoresis and, ocasionally, fainting, started one year before. She had had acute pulmonary edema and a cardiorespiratory arrest during her first caesarean section. A CT scan revealed a right adrenal tumor (6.0 cm), showing increased 123I-MIBG uptake. After conventional adrenalectomy, a PHEO was immunohistochemically confirmed. Close follow-up has shown no signs of recurrence or evidence of new tumors.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.Q164R (c.491A>G)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 2238 https://www.ncbi.nlm.nih.gov/clinvar/variation/2238/

CAID: N/A

gnomAD: N/A

VariantEvidence: To date, this germline VHL mutation was said to have been described in only 3 cases, with variable phenotypes, and in 2 cases PHEO occurred at a very young age.

MutationType: missense_variant;transition

CivicName: N/A

MultipleGeneVariants: N/A