Clinical Variant Reclassification in Hereditary Disease Genetic Testing
In this cohort study of individuals undergoing genetic testing, the empirically estimated accuracy of pathogenic, likely pathogenic, benign, and likely benign classifications exceeded the certainty thresholds set by current VC guidelines, suggesting the need to reevaluate definitions of these classifications. The relative contribution of various strategies to resolve VUS, including emerging machine learning-based computational methods, RNA analysis, and cascade family testing, provides useful insights that can be applied toward further improving VC methods, reducing the rate of VUS, and generating more definitive results for patients.
Authors
- Swaroop Aradhya (ORCID: https://orcid.org/0000-0001-6219-2931)
- Britt Johnson (ORCID: https://orcid.org/0000-0003-1883-5201)
- Sarah Poll (ORCID: https://orcid.org/0000-0001-7324-9825)
- Elaine Chen (ORCID: https://orcid.org/0000-0001-5446-137X)
- Dan Swartzlander
- Flavia M. Facio (ORCID: https://orcid.org/0000-0002-7472-471X)
- Hillery C. Metz (ORCID: https://orcid.org/0000-0002-8246-3513)
- Yuya Kobayashi (ORCID: https://orcid.org/0000-0002-8202-2101)
Institutions
- Illumina (United States) (US)
- LabCorp (United States) (US)
- Invitae (United States) (US)
- Stanford University (US)
Publication Details
- Journal
- JAMA Network Open
- Published
- 2024-11-06
- DOI
- https://doi.org/10.1001/jamanetworkopen.2024.44526
- Citations
- 28
- Primary Topic
- Genomics and Rare Diseases
- Type
- article
- Field-Weighted Citation Impact
- 15.41