GroupID: None (12)

DiseaseAssertion: VHL

GroupSize: 1

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: N/A

GroupAgeRange: N/A

GroupInfo: This family group of 1 individual has clinically confirmed VHL disease presenting with retinal angiomatosis. This individual was found to harbor a c.278G>T variant causing a Gly93Val missense mutation (noted in the paper as c.491G>T due to Latif reference transcript being used).

GroupPresentingHPOs: HP:0009711 (Retinal capillary hemangioma)

GroupHPOFreeText: Patients within this family were found to have a clinical diagnosis of VHL disease. No VHL clinical phenotypes were explicitly stated other than retinal angiomatosis.

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.G93V (c.278G>T)

LegacyVariant: c.491G>T

CaseProblemVariantFreeText: N/A

ClinVarID: 625232, https://www.ncbi.nlm.nih.gov/clinvar/variation/625232/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: G93V (c.278G>T)

MultipleGeneVariants: N/A

PatientID: N/A

KindredID: 1

Case: F, 10Y0M, Ethnicity Unknown

DiseaseAssertion: Assumed VHL

FamilyInfo: No family history, authors indicate that the variant occurred de novo.

CasePresentingHPOs: HP:0007514; HP:0000017; HP:0004421; HP:0012594; HP:0002666; HP:0001920 (Edema of the dorsum of hands; Nocturia; Elevated systolic blood pressure; Moderate albuminuria; Pheochromocytoma; Renal artery stenosis)

CaseHPOFreeText: Patient presented with occasional high routine blood pressure at 10Y0M. She noted mild hand edema over the past days and reported recent nocturia. Physical examination appeared normal other than elevated blood pressure of 139/113 mm Hg. Urine tests showed moderate albuminuria (albumin-creatinine ratio of 50 mg/g), as well as high levels of noradrenaline and normetanephrine, suggestive of benign pheochromocytoma. Ultrasound showed normal kidney size and parenchyma, but color duplex sonography revealed increased flow rate of the left renal artery. This finding suggests renal artery stenosis. Magnetic Resonance Angiography of the kidney vessels showed a solid tumor that had cystic features. Tumor resection normalized blood pressure and pathologic examination of the removed tumor confirmed pheochromocytoma. Patient was diagnosed with secondary hypertension due to compression of renal vessels and catecholamine production by vHL-associated pheochromocytoma. Antihypertensive therapy with phenoxybenzamine as α blockade was initiated, along with subsequent expansion of the therapy with a β-blocker. Authors mention that the patient is in complete remission with no other manifestations of VHL disease and is receiving close follow-up.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.G104V (c.311G>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 223183, https://www.ncbi.nlm.nih.gov/clinvar/variation//223183/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: G104V (c.311G>T)

MultipleGeneVariants: N/A

PatientID: None

KindredID: 1

Case: F, 17Y0M, Ethnicity Unknown

DiseaseAssertion: Retinal hemangioblastoma

FamilyInfo: The heterozygous missense variant NM_000551.3:c.311G>T was identified on her 21-year-old sister and her mother, but not her father. The sister had hypertension and a paraganglioma. The patient’s mother had refused a complete staging.

CasePresentingHPOs:HP:0009711 (Retinal hemangioblastoma)

CaseHPOFreeText: The patient’s evaluation was normal with the exception of a small retinal hemangioblastoma.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.G104V(c.311G>T)

LegacyVariant: N/A

ClinVarID: 223183, http://www.ncbi.nlm.nih.gov/clinvar/variation/223183

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: G104V(c.311G>T)

MultipleGeneVariants: N/A

PatientID: None

KindredID: 1

Case: F, Age Unknown, Ethnicity Unknown

DiseaseAssertion: Asymptomatic

FamilyInfo: The heterozygous missense variant NM_000551.3:c.311G>T was identified on two of her daughters; one was 21Y and one was 17Y. The 21Y daughter had hypertension and a paraganglioma, and the 17Y daughter had a retinal hemangioblastoma.

CasePresentingHPOs: N/A

CaseHPOFreeText: The patient refused a complete staging.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.G104V(c.311G>T)

LegacyVariant: N/A

ClinVarID: 223183, http://www.ncbi.nlm.nih.gov/clinvar/variation/223183

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: G104V(c.311G>T)

MultipleGeneVariants: N/A

GroupID: 13

Case: Sex unknown, Age unknown, German

DiseaseAssertion: VHL

FamilyInfo: Unknown. 1 registrant was found with this variant; no family info was mentioned

CasePresentingHPOs: HP:0030393 (Endolymphatic sac tumor)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.G114Vfs*45 (c.339delA)

CaseProblemVariantFreeText: N/A

LegacyVariant: N/A

ClinVarID: N/A

CAID: CA645509026 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.339delA

gnomAD: N/A

VariantEvidence: N/A

MutationType: minus_1_frameshift_variant

CivicName: G114Vfs*45 (c.339delA)

MultipleGeneVariants: N/A

PatientID: HGB-19

KindredID: 4

Case: Sex Unknown, 44Y0M, Italian

DiseaseAssertion: VHL

FamilyInfo: None.

CohortInfo: The patient cohort consisted of 57 patients (26 male and 31 female) from Southern Italy, most of whom (55 of 57) presented with solitary HGB of the CNS: 6 were syndromic and 51 were apparently sporadic.

CasePresentingHPOs: HP:0006880, HP:0009713 (cerebellar hemangioblastoma, spinal hemangioblastoma)

CaseHPOFreeText: The patient had a single cerebellar hemangioblastoma that was diagnosed at age 32. The patient had a spinal cord hemangioblastoma at age 40.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.G114V(c.341G>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351753604 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.341G%3ET

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transversion

CivicName: G114V (c.341G>T)

MultipleGeneVariants: N/A