{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T19:52:39Z","timestamp":1785268359146,"version":"3.55.0"},"reference-count":128,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"19","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,10,4]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">As utilization of clinical exome sequencing (ES) has expanded, criteria for evaluating the diagnostic weight of incidentally identified variants are critical to guide clinicians and researchers. This is particularly important in genes associated with dilated cardiomyopathy (DCM), which can cause heart failure and sudden death. We sought to compare the frequency and distribution of incidentally identified variants in DCM\u2010associated genes between a clinical referral cohort with those in control and known case cohorts to determine the likelihood of pathogenicity among those undergoing genetic testing for non\u2010DCM indications.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              A total of 39 rare, non\u2010\n              <jats:italic>TTN<\/jats:italic>\n              DCM\u2010associated genes were identified and evaluated from a clinical ES testing referral cohort (n=14\u2009005, Baylor Genetic Laboratories) and compared with a DCM case cohort (n=9442) as well as a control cohort of population variants (n=141\u2009456) derived from the gnomAD database. Variant frequencies in each cohort were compared. Signal\u2010to\u2010noise ratios were calculated comparing the DCM and ES cohort with the gnomAD cohort. The likely pathogenic\/pathogenic variant yield in the DCM cohort (8.2%) was significantly higher than in the ES cohort (1.9%). Based on signal\u2010to\u2010noise and correlation analysis, incidental variants found in\n              <jats:italic>FLNC<\/jats:italic>\n              ,\n              <jats:italic>RBM20<\/jats:italic>\n              ,\n              <jats:italic>MYH6<\/jats:italic>\n              ,\n              <jats:italic>DSP<\/jats:italic>\n              ,\n              <jats:italic>ABCC9<\/jats:italic>\n              ,\n              <jats:italic>JPH2<\/jats:italic>\n              , and\n              <jats:italic>NEXN<\/jats:italic>\n              had the greatest chance of being DCM\u2010associated.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">The distribution of pathogenic variants between the ES cohort and the DCM case cohort was gene specific, and variants found in the ES cohort were similar to variants found in the control cohort. Incidentally identified variants in specific genes are more associated with DCM than others.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.025257","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T10:40:26Z","timestamp":1663756826000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Determining the Likelihood of Disease Pathogenicity Among Incidentally Identified Genetic Variants in Rare Dilated Cardiomyopathy\u2010Associated Genes"],"prefix":"10.1161","volume":"11","author":[{"given":"Qixin","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Cardiology Duke University School of Medicine Durham NC"},{"name":"Department of Cardiology The First Affiliated Hospital, College of Medicine, Zhejiang University Hangzhou 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