PatientID: 21

KindredID: 12

Case: F, 27Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: N/A

CohortInfo: Thirty-nine cases of sporadic or familial pheo/PGL and pituitary adenomas were investigated.

CasePresentingHPOs: HP:0002893; HP:0002666 (Pituitary adenoma, Pheochromocytoma)

CaseHPOFreeText: Pituitary adenoma presented at age 27. Pheochromocytoma age of presentation unknown.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: MAX/RET/TMEM127/SDHA/SDHB/SDHC/SDHD/SDHAF2

PreviouslyPublished: N/A

SupplementalData: Table 1, Supplementary Table 6

Variant: p.D197N (c.589G>A)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351756524, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_canonicalid?canonicalid=CA351756524

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: D197N (c.589G>A)

MultipleGeneVariants: Germline, SDHA, c.91C>T (p.Arg31*)

GroupID: 6

Case: Age unknown, Sex unknown, French

DiseaseAssertion: VHL

FamilyInfo: None - one member documented here

CasePresentingHPOs: HP:0009711 (retinal capillary hemangioma)

CaseHPOFreeText: other manifestations are not clearly stated.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.N67_V74del (c.197_220del)

CaseProblemVariantFreeText: Paper describes this as a frameshift via c.197del24 (p.66)

LegacyVariant: N/A

ClinVarID: N/A

CAID: CA645524685 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.197_220del

gnomAD: N/A

VariantEvidence: N/A

MutationType: inframe_deletion

CivicName: N67_V74del (c.197_220del)

MultipleGeneVariants: N/A

PatientID: 3

KindredID: 3

Case: M, 15Y0M, Ethnicity Unknown

DiseaseAssertion: adrenal pheochromocytoma

FamilyInfo: None - The family history was negative for hypertension, PHEO or other neuroendocrine tumours. Their parents however, decided not to be tested neither to extend the test to other family members

CasePresentingHPOs: HP:0006748 (adrenal pheochromocytoma)

CaseHPOFreeText: Apparently sporadic pheo. He had a history of occipital headache, slightly elevated blood pressure with normal ophthalmological examination for 2 months was found to have a 4-cm-diameter left adrenal mass at MRI, being the abdominal sonography negative. He underwent surgery of the pheochromocytoma.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET, SDHB, SDHD

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.D197N (c.589G>A)

LegacyVariant: p.D197N (g.13,278)

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351756524 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.589G%3EA

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: D197N (c.589G>A)

MultipleGeneVariants: N/A

GroupID: 287

DiseaseAssertion: VHL

GroupSize: 2

GroupNumberMales: N/A

GroupNumberFemales: N/A

GroupEthnicity: French

GroupAgeRange: N/A

GroupInfo: 2 members of this family are reported as carrying the c.197_220del24 germline variant of the VHL gene. Member 6396 presented with mild renal disease. Member 6611 presented with severe renal disease (RCC). Families were recruited from the French VHL Registry. Enrolment in the study required identification of the germline VHL mutation (currently 85% of the families included in the French VHL Registry) and available data regarding renal phenotype. A total of 126 families fulfilled these criteria.

GroupPresentingHPOs: HP:0009726; HP:0005584 (Renal neoplasm, Renal cell carcinoma)

GroupHPOFreeText: Mild renal disease (simple renal cyst, multicystic kidney[s], small lesion [less than 10 mm in size] of unknown significance, or small solid tumor without indication for surgical removal [less than 30 mm in size]). Severe renal disease (any solid lesion before 25 years of age, five or more solid lesions within one or two kidneys, or metastasis of renal cell carcinoma).

GroupNotHPOs: N/A

GroupNotHPOFreeText: N/A

GroupPreviousTesting: N/A

PreviouslyPublished: Paper states that this family is previously reported in PMID 9829912, where 1 patient with this mutation is reported but relation to this patient is unclear.

SupplementalData: Phenotype and genotype information can be found in Supplementary Table S1.

Variant: p.N67_V74del (c.197_221del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA2573130203, https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA2573130203

gnomAD: N/A

VariantEvidence: Variant reported as c.197_220del and was mapped to c.198_221del.

MutationType: inframe_deletion; deletion

CivicName: N67_V74del (c.197_221del)

MultipleGeneVariants: N/A

PatientID: 2

KindredID: 2

Case: F, 17Y0M, Ethnicity Unknown

DiseaseAssertion: adrenal pheochromocytoma

FamilyInfo: None - The family history was negative for PHEO or other neuroendocrine tumours. Their parents however, decided not to be tested neither to extend the test to other family members

CasePresentingHPOs: HP:0006748 (adrenal pheochromocytoma)

CaseHPOFreeText: Apparently sporadic pheo. She had a history of primitive headache, intense nocturnal sweating and 2-month-long amenorrhoea and elevated blood pressure presented a 7-cm-diameter right adrenal mass at abdominal sonography, confirmed by MRI.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: RET, SDHB, SDHD

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.D197N (c.589G>A)

LegacyVariant: p.D197N (g.13,278)

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: CA351756524 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvsOrDescriptor=NM_000551.3%3Ac.589G%3EA

gnomAD: N/A

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName: D197N (c.589G>A)

MultipleGeneVariants: N/A