Clinical Laboratories Collaborate to Resolve Differences in Variant Interpretations Submitted to ClinVar

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Clinical Laboratories Collaborate to Resolve Differences in Variant Interpretations Submitted to ClinVar

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Title: Clinical Laboratories Collaborate to Resolve Differences in Variant Interpretations Submitted to ClinVar
Author: Harrison, Steven M.; Dolinsky, Jill S.; Knight Johnson, Amy E.; Pesaran, Tina; Azzariti, Danielle R.; Bale, Sherri; Chao, Elizabeth C.; Das, Soma; Vincent, Lisa; Rehm, Heidi L.

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Citation: Harrison, Steven M., Jill S. Dolinsky, Amy E. Knight Johnson, Tina Pesaran, Danielle R. Azzariti, Sherri Bale, Elizabeth C. Chao, Soma Das, Lisa Vincent, and Heidi L. Rehm. 2017. “Clinical Laboratories Collaborate to Resolve Differences in Variant Interpretations Submitted to ClinVar.” Genetics in medicine : official journal of the American College of Medical Genetics 19 (10): 1096-1104. doi:10.1038/gim.2017.14. http://dx.doi.org/10.1038/gim.2017.14.
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Abstract: Purpose Data sharing through ClinVar offers a unique opportunity to identify interpretation differences between laboratories. As part of a ClinGen initiative, four clinical laboratories (Ambry, GeneDx, Partners Healthcare Laboratory for Molecular Medicine, and University of Chicago Genetic Services Laboratory) collaborated to identify the basis of interpretation differences and to investigate if data sharing and reassessment resolves interpretation differences by analyzing a subset of variants. Methods: ClinVar variants with submissions from at least two of the four participating laboratories were compared. For a subset of identified differences, laboratories documented the basis for discordance, shared internal data, independently reassessed with the ACMG-AMP guidelines, and then compared interpretations. Results: 6,169 variants in ClinVar were interpreted by at least two of the participating laboratories, of which 88.3% were initially concordant. Laboratories reassessed 242/724 initially discordant variants, of which 87.2% (211) were resolved by reassessment with current criteria and/or internal data sharing. 12.8% (31) of reassessed variants remain discordant due to differences in application of the ACMG-AMP guidelines. Conclusion: Participating laboratories increased their overall concordance from 88.3% to 91.7%, indicating that sharing variant interpretations in ClinVar, allowing identification of differences and motivation to resolve those differences, is critical to move toward more consistent variant interpretations.
Published Version: doi:10.1038/gim.2017.14
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5600649/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:34492223
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