title: DATA SHARING AND REPRODUCIBLE CLINICAL GENETIC TESTING: SUCCESSES AND CHALLENGES.
abstract: Open sharing of clinical genetic data promises to both monitor and eventually improve the reproducibility of variant interpretation among clinical testing laboratories. A significant public data resource has been developed by the NIH ClinVar initiative, which includes submissions from hundreds of laboratories and clinics worldwide. We analyzed a subset of ClinVar data focused on specific clinical areas and we find high reproducibility (>90% concordance) among labs, although challenges for the community are clearly identified in this dataset. We further review results for the commonly tested BRCA1 and BRCA2 genes, which show even higher concordance, although the significant fragmentation of data into different silos presents an ongoing challenge now being addressed by the BRCA Exchange. We encourage all laboratories and clinics to contribute to these important resources.
authors.affiliation: Invitae, San Francisco, California, USA, shan.yang@invitae.com.
authors.forename: Shan
authors.initials: S
authors.lastname: Yang
authors.forename: Melissa
authors.initials: M
authors.lastname: Cline
authors.forename: Can
authors.initials: C
authors.lastname: Zhang
authors.forename: Benedict
authors.initials: B
authors.lastname: Paten
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Lincoln
mesh_terms: D019295:Computational Biology; D030541:Databases, Genetic / Q000706:statistics & numerical data; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005820:Genetic Testing / Q000706:statistics & numerical data*; D014644:Genetic Variation; D006801:Humans; D033181:Information Dissemination / Q000379:methods*; D009316:National Institutes of Health (U.S.); D015203:Reproducibility of Results; D014481:United States