PatientID: B22

KindredID: 3

Case: Sex Unknown, Age Unknown, Lebanese

DiseaseAssertion: breast cancer

FamilyInfo: Familial breast cancer noted; no other specifics provided.

CasePresentingHPOs: HP:0003002 (breast carcinoma)

CaseHPOFreeText: Patient has familial breast cancer (table 2).

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.M221L (c.631A>C)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 182990, https://www.ncbi.nlm.nih.gov/clinvar/variation/182990/

CAID: N/A

gnomAD: 0.00002127, https://gnomad.broadinstitute.org/variant/3-10191638-A-C

VariantEvidence: N/A

MutationType: missense_variant; transversion

CivicName: M221L (c.631A>C)

MultipleGeneVariants: Germline, BRCA2, c.5744C>T (p.T1915M); Germline, ARL11, c.446G>A (p.W149*); Germline, TP53, c.215C>G (p.P72R); Germline, ERCC3, c.508C>T (p.R170X); Germline, MRE11A, c.1491C>T (p.I497I); Germline, PTCH1, c.4054G>A (p.V1352I)

PatientID: BCB-D-59

KindredID: 1

Case: Sex Unknown, Age Unknown, Saudi

DiseaseAssertion: Breast carcinoma

FamilyInfo: No family information reported.

CasePresentingHPOs: HP:0003002 (breast carcinoma)

CaseHPOFreeText: Patient has breast carcinoma. No other information is provided.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Ion AmpliSeq™ BRCA1 and BRCA2 Panel.

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.E52* (c.154G>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 182982, https://www.ncbi.nlm.nih.gov/clinvar/variation/182982/

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: stop_gained

CivicName: E52* (c.154G>T)

MultipleGeneVariants: Germline, TP53, c.241C>T (p.R81X); Germline, MLH1, c.208-1G>C (p.E52X)

PatientID: None

KindredID: 1

Case: F, 52Y0M, Danish

DiseaseAssertion: Breast carcinoma

FamilyInfo: The patient had three sons all of whom carried the VHL mutation. Two of the sons were asymptomatic and one had renal cell carcinoma. The affected son also had a P2P mutation and he had a child who was found to have the VHL mutation (P2P). The patient's mother had the mutation but was also asymptomatic. See Figure 1 for family pedigree.

CasePresentingHPOs: HP:0003002 (Breast carcinoma)

CaseHPOFreeText: The patient had breast cancer at age 34.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: p.P81S (c.241C>T)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: 2233 https://www.ncbi.nlm.nih.gov/clinvar/variation/2233/

CAID: N/A

gnomAD: 0.0002179 https://gnomad.broadinstitute.org/variant/3-10183772-C-T

VariantEvidence: N/A

MutationType: missense_variant;transition

CivicName:P81S (c.241C>T)

MultipleGeneVariants: N/A

PatientID: 2

KindredID: 1

Case: F, 54Y0M, Ethnicity Unknown

DiseaseAssertion: VHL

FamilyInfo: Son (id:1) with the same variant, presenting with cerebellar hemangioblastoma at age 18, spinal hemangioblastomas at ages 19 and 31 and renal cysts but the age of onset for these is not noted. Father (id: 3) presented with cerebellar hemangioblastoma at age 65. Paternal uncle (id: 4) presented with prostate cancer at age 65. Paternal grandfather (id: 5) presented with cerebellar hemangioblastomas at age 69. Mother and daughter did not have the mutation. Her father was not tested. No family history of retinal capillary hemangiomas or pheochromocytoma.

CasePresentingHPOs: HP:0006880; HP:0005584; HP:0003002 (Cerebellar hemangioblastoma, Renal cell carcinoma, Breast carcinoma)

CaseHPOFreeText: Bilateral breast cancer at age 46 and 49. First cancer was diagnosed at the age of 46 in her right breast. The patient was treated by mastectomy with postoperative chemotherapy (CMF). Histopathological examination revealed invasive ductal breast carcinoma. A metastasis in 1 axillary lymph node was found. There was no evidence of distant metastases. Three years later, at the age of 49, she was diagnosed with cancer of her left breast. It was an invasive ductal carcinoma. There was no evidence for lymph-node or distant metastases. At present, 9 and 6 years after treatment of the breast cancers there is no evidence of breast cancer recurrence. However at age of 54, lesions typical for VHL disease including cerebellar haemangioblastoma and renal cell carcinoma were diagnosed in the patient.

CaseNotHPOs: HP:0002666; HP:0009711 (Pheochromocytoma, Retinal capillary hemangioma)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

PreviouslyPublished: N/A

SupplementalData: Figure 1 (pedigree) and Table 1 (phenotype and age of onset data).

Variant: Exon 1 Deletion (c.1-?_340+?del)

LegacyVariant: N/A

CaseProblemVariantFreeText: N/A

ClinVarID: N/A

CAID: N/A

gnomAD: N/A

VariantEvidence: N/A

MutationType: exon_loss_variant

CivicName: Exon 1 Deletion

MultipleGeneVariants: Germline, FANCD2, Partial Deletion