Diagnosis; Mutation Confirmation; Pre-symptomatic; Predictive; Prognostic; Recurrence; Risk Assessment

A germline mutation in BRCA1 or BRCA2 predisposes to breast and ovarian cancer as well as other cancers. The risk of developing cancer that is associated with a germline BRCA1 or BRCA2 mutation, which has been derived from families with multiple affected individuals, families with few affected individuals, and from … A germline mutation in BRCA1 or BRCA2 predisposes to breast and ovarian cancer as well as other cancers. The risk of developing cancer that is associated with a germline BRCA1 or BRCA2 mutation, which has been derived from families with multiple affected individuals, families with few affected individuals, and from population-based studies, appears to be variable within families. Prognosis for breast and ovarian cancer depends on the stage at which the cancer is diagnosed; however, studies on survival have revealed conflicting results for individuals with germline BRCA1 or BRCA2 mutations when compared to controls. View more

Avoidance of invasive testing

Establish or confirm diagnosis

Guidance for management

Predictive risk information for patient and/or family members

Molecular genetic testing for germline BRCA1 and BRCA2 mutations is available on a clinical basis for individuals who are identified to be at high risk based on their personal and/or family history and for at-risk relatives of an individual with an identified germline BRCA1 or BRCA2 mutation. No currently available … Molecular genetic testing for germline BRCA1 and BRCA2 mutations is available on a clinical basis for individuals who are identified to be at high risk based on their personal and/or family history and for at-risk relatives of an individual with an identified germline BRCA1 or BRCA2 mutation. No currently available technique can guarantee the identification of all cancer-predisposing mutations in BRCA1 or BRCA2. Furthermore, mutations of uncertain clinical significance may be identified. View more

All coding exons and 20 bp of flanking non-coding sequence are enriched using an LHSC custom targeted hybridization protocol (Roche Nimblegen), followed by high throughput sequencing (Illumina). Sequence variants and copy number changes are assessed and interpreted using clinically validated algorithms and commercial software (SoftGenetics: Nextgene, Geneticist Assistant, Mutation Surveyor; … All coding exons and 20 bp of flanking non-coding sequence are enriched using an LHSC custom targeted hybridization protocol (Roche Nimblegen), followed by high throughput sequencing (Illumina). Sequence variants and copy number changes are assessed and interpreted using clinically validated algorithms and commercial software (SoftGenetics: Nextgene, Geneticist Assistant, Mutation Surveyor; and Alamut Visual). All exons have >300x mean read depth coverage, with a minimum 100x coverage at a single nucleotide resolution. This assay meets the sensitivity and specificity of combined Sanger sequencing and MLPA copy number analysis. Variants interpreted as either ACMG category 1, 2, or 3 (pathogenic, likely pathogenic, VUS; PMID: 25741868), if necessary, are confirmed using Sanger sequencing, MLPA, or other assays. ACMG category 4 and 5 variants (likely benign, benign) are not reported, but are available upon request. Variants detected in the 5’ UTR and 3’ UTR are not reported unless there is evidence suggesting pathogenicity. This assay has been validated at a level of sensitivity equivalent to the Sanger sequencing and standard copy number analysis (>99%; PMID: 27376475,28818680). View more

Variants interpreted as either ACMG category 1, 2, or 3 (pathogenic, likely pathogenic, VUS; PMID: 25741868), if necessary, are confirmed using Sanger sequencing, MLPA, or other assays.

Tests performed
Entire test performed in-house

Test performance comments
Testing is performed in a licensed purpose built facility located in a major regional medical health care facility

This assay has been validated at a level of sensitivity equivalent to the Sanger sequencing and standard copy number analysis (>99%; PMID: 27376475,28818680).

Is proficiency testing performed for this test? Help
Yes

Method used for proficiency testing: Help
Formal PT program

PT Provider: Help
American College of Medical Genetics / College of American Pathologists, ACMG/CAP

Software used to interpret novel variations Help
(SoftGenetics: Nextgene, Geneticist Assistant, Mutation Surveyor; and Alamut Visual).

Laboratory's policy on reporting novel variations Help
All variants interpreted as either ACMG category 1, 2, or 3 (pathogenic, likely pathogenic, VUS; PMID: 25741868) if necessary are confirmed using Sanger sequencing, MLPA, or other assays. ACMG category 4 and 5 variants (likely benign, benign) are not reported, but are available upon request.