Dataset Information

Clinical validity assessment of genes for inclusion in multi-gene panel testing: A systematic approach.

ABSTRACT:

Background

Advances in sequencing technology have led to expanded use of multi-gene panel tests (MGPTs) for clinical diagnostics. Well-designed MGPTs must balance increased detection of clinically significant findings while mitigating the increase in variants of uncertain significance (VUS). To maximize clinical utililty, design of such panels should include comprehensive gene vetting using a standardized clinical validity (CV) scoring system.

Methods

To assess the impact of CV-based gene vetting on MGPT results, data from MGPTs for cardiovascular indications were retrospectively analyzed. Using our CV scoring system, genes were categorized as having definitive, strong, moderate, or limited evidence. The rates of reported pathogenic or likely pathogenic variants and VUS were then determined for each CV category.

Results

Of 106 total genes, 42% had definitive, 17% had strong, 29% had moderate, and 12% had limited CV. The detection rate of variants classified as pathogenic or likely pathogenic was higher for genes with greater CV, while the VUS rate showed an inverse relationship with CV score. No pathogenic or likely pathogenic findings were observed in genes with a limited CV.

Conclusion

These results demonstrate the importance of a standardized, evidence-based vetting process to establish CV for genes on MGPTs. Using our proposed system may help to increase the detection rate while mitigating higher VUS rates.

SUBMITTER: Zion TN

PROVIDER: S-EPMC6503028 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Clinical validity assessment of genes for inclusion in multi-gene panel testing: A systematic approach.

Zion Tricia N TN Wayburn Bess B Darabi Sourat S Lamb Thrush Devon D Smith Erica D ED Johnston Tami T Martin Brissa B Hagman Kelly D F KDF Parra Melissa M Antolik Christian C

Molecular genetics & genomic medicine 20190321 5

<h4>Background</h4>Advances in sequencing technology have led to expanded use of multi-gene panel tests (MGPTs) for clinical diagnostics. Well-designed MGPTs must balance increased detection of clinically significant findings while mitigating the increase in variants of uncertain significance (VUS). To maximize clinical utililty, design of such panels should include comprehensive gene vetting using a standardized clinical validity (CV) scoring system.<h4>Methods</h4>To assess the impact of CV-ba ...[more]

PMID: 30900393

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Dataset Information

Clinical validity assessment of genes for inclusion in multi-gene panel testing: A systematic approach.

Background

Methods

Results

Conclusion

Publications

Clinical validity assessment of genes for inclusion in multi-gene panel testing: A systematic approach.

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