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Diagnostic testing laboratories are valuable partners for disease gene discovery: 5-year experience with GeneMatcher
  • +5
  • Meghan Towne,
  • Mari Rossi,
  • Bess Wayburn,
  • Jennifer Huang,
  • Kelly Radtke,
  • Wendy Alcaraz,
  • Kelly Farwell,
  • Deepali Shinde
Meghan Towne
Ambry Genetics Corp

Corresponding Author:mtowne@ambrygen.com

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Mari Rossi
Ambry Genetics Corp
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Bess Wayburn
Ambry Genetics Corp
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Jennifer Huang
Ambry Genetics Corp
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Kelly Radtke
Ambry Genetics Corp
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Wendy Alcaraz
Ambry Genetics Corp
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Kelly Farwell
Ambry Genetics Corp
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Deepali Shinde
Ambry Genetics Corp
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Abstract

Clinical and research laboratories extensively use exome sequencing due to its high diagnostic rates, cost savings, impact on clinical management, and efficacy for disease gene discovery. While the rates of disease gene discovery have steadily increased, only ~16% of genes in the genome have confirmed disease associations. Here we describe our diagnostic laboratory’s disease gene discovery and ongoing data-sharing efforts with GeneMatcher. In total, we submitted 246 candidates from 243 unique genes to GeneMatcher, of which 45.93% are now clinically characterized. Submissions with at least one case meeting our candidate genes reporting criteria were significantly more likely to be characterized as of October 2021 compared to genes with no candidates meeting our reporting criteria (p=0.025). We reported relevant findings related to these gene-disease associations for 480 probands. In 219 (45.63%) instances, these results were reclassifications after an initial candidate gene (uncertain) or negative report. Since 2013, we have co-authored 105 publications focused on delineating gene-disease associations. Diagnostic laboratories are pivotal for disease gene discovery efforts and can screen phenotypes based on genotype matches, contact clinicians of relevant cases, and issue proactive reclassification reports. GeneMatcher is a critical resource in these efforts.
23 Oct 2021Submitted to Human Mutation
23 Oct 2021Submission Checks Completed
23 Oct 2021Assigned to Editor
26 Oct 2021Reviewer(s) Assigned
18 Nov 2021Review(s) Completed, Editorial Evaluation Pending
30 Nov 2021Editorial Decision: Revise Minor
01 Feb 20221st Revision Received
02 Feb 2022Submission Checks Completed
02 Feb 2022Assigned to Editor
06 Feb 2022Review(s) Completed, Editorial Evaluation Pending
08 Feb 2022Editorial Decision: Accept
02 Mar 2022Published in Human Mutation. 10.1002/humu.24342