Diagnosis; Mutation Confirmation; Pre-symptomatic; Risk Assessment

Individuals at risk for a variety of hereditary cancer syndromes based on assessment of their personal and family cancer history.

All potential clinically significant variants are independently confirmed by repeated PCR amplification of the indicated gene region (s) and NGS.

All potential clinically significant variants are independently confirmed by repeated PCR amplification of the indicated gene region (s) and NGS.

Previousy registered in GTR as GTR000530028

Tests performed
Entire test performed in-house

Analytical specificity The incidence of a false report of a genetic variant or mutation resulting from technical error is considered negligible because of independent confirmation of all clinically significant genetic variants (see above). The incidence of a false report of a clinically significant genetic variant or mutation resulting from errors … Analytical specificity The incidence of a false report of a genetic variant or mutation resulting from technical error is considered negligible because of independent confirmation of all clinically significant genetic variants (see above). The incidence of a false report of a clinically significant genetic variant or mutation resulting from errors in specimen handling and tracking is estimated from validation studies to be less than one percent (<1%). Analytical sensitivity Failure to detect a genetic variant or mutation in the analyzed DNA regions may result from errors in specimen handling and tracking, amplification and sequencing reactions, or computer-assisted analysis and data review. The rate of such errors is estimated from validation studies to be less than one percent (<1%). The analytical sensitivity of next-generation sequencing for genes in the myRisk test was 100% (99.96%-100%, 95% C.I.) and the analytical specificity was 100% (99.99%-100%, 95% C.I.) based on complete concordance in comparative studies to validated reference methods performed on 238 individual anonymized DNA samples extracted from blood or saliva with 9,303 identified sequence variants for genes in the myRisk test. Large Rearrangement Validation Validation studies for large rearrangement detection using NGS dosage analysis were performed using DNA samples extracted from blood and buccal saliva samples. These included 308 samples that had previously tested positive for large rearrangement mutations, which were all successfully detected by NGS dosage analysis of the genes in the myRisk panel. All reviewable results for large rearrangements were 100% concordant. Test reproducibility The 1st comparative analytical validation study included a reproducibility sample set comprised of 4 individual anonymized DNA samples extracted from blood, collectively carrying 199 sequence variants confirmed by Sanger sequencing. The 2nd study included a reproducibility sample set comprised of anonymized DNA extracted from 4 contributors who donated paired blood and saliva samples, collectively carrying 121 sequence variants which were found to be concordant between saliva and blood. In both studies, each of the 4 anonymized samples was sequenced by NGS in triplicate across three batches (i.e., 4 samples x 9 replicates each) which demonstrated 100% reproducibility. View more

Limitations of method Unequal allele amplification may result from rare polymorphisms under PCR primer sites. The presence of pseudogenes may complicate the detection of rare sequencing and large rearrangement mutations in certain genes. There may be uncommon genetic abnormalities such as specific insertions, inversions, and certain regulatory mutations that will … Limitations of method Unequal allele amplification may result from rare polymorphisms under PCR primer sites. The presence of pseudogenes may complicate the detection of rare sequencing and large rearrangement mutations in certain genes. There may be uncommon genetic abnormalities such as specific insertions, inversions, and certain regulatory mutations that will not be detected by myRisk. This analysis, however, is believed to rule out the majority of abnormalities in the genes analyzed. Genetic testing results on blood or buccal saliva samples may not reflect the germline genetic status of patients with a hematologic malignancy, or patients who underwent allogeneic bone marrow transplants. In such cases, please contact Medical Services to discuss re-submission of an appropriate sample type. View more

Is proficiency testing performed for this test? Help
Yes

Method used for proficiency testing: Help
Formal PT program

PT Provider: Help
College of American Pathologists

Description of PT method: Help
Blinded internal proficiency testing.

Software used to interpret novel variations Help
In house developed analytical tools.

Laboratory's policy on reporting novel variations Help
All non-polymophism variations are reported.