{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:25:29Z","timestamp":1791231929013,"version":"4.1.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>\n              The hypothesis of the Dilated Cardiomyopathy Precision Medicine Study is that most dilated cardiomyopathy has a genetic basis. The study returns results to probands and, when indicated, to relatives. While both the American College of Medical Genetics and Genomics\/Association for Molecular Pathology and ClinGen\u2019s\n              <jats:italic>MYH7<\/jats:italic>\n              -cardiomyopathy specifications provide relevant guidance for variant interpretation, further gene- and disease-specific considerations were required for dilated cardiomyopathy. To this end, we tailored the ClinGen\n              <jats:italic>MYH7<\/jats:italic>\n              -cardiomyopathy variant interpretation framework; the specifications implemented for the study are presented here.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>\n              Modifications were created and approved by an external Variant Adjudication Oversight Committee. After a pilot using 81 probands, further adjustments were made, resulting in 27 criteria (9 modifications of the ClinGen\n              <jats:italic>MYH7<\/jats:italic>\n              framework and reintroduction of 2 American College of Medical Genetics and Genomics\/Association of Molecular Pathology criteria that were deemed not applicable by the ClinGen\n              <jats:italic>MYH7<\/jats:italic>\n              working group).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>These criteria were applied to 2059 variants in a test set of 97 probands. Variants were classified as benign (n=1702), likely benign (n=33), uncertain significance (n=71), likely pathogenic (likely pathogenic; n=12), and pathogenic (P; n=3). Only 2\/15 likely pathogenic\/P variants were identified in Non-Hispanic African ancestry probands.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>\n              We tailored the ClinGen\n              <jats:italic>MYH7<\/jats:italic>\n              criteria for our study. Our preliminary data show that 15\/97 (15.5%) probands have likely pathogenic\/P variants, most of which were identified in probands of Non-Hispanic European ancestry. We anticipate continued evolution of our approach, one that will be informed by new insights on variant interpretation and a greater understanding of the genetic architecture of dilated cardiomyopathy.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical Trial Registration:<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT03037632\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgen.119.002480","type":"journal-article","created":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T18:00:55Z","timestamp":1587492055000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":114,"title":["Variant Interpretation for Dilated Cardiomyopathy"],"prefix":"10.1161","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct03037632","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Ana","family":"Morales","sequence":"first","affiliation":[{"name":"Division of Human Genetics, Department of Internal Medicine (A.M., D.D.K., E.J., C.S., J.M., T.A., R.E.H.), The Ohio State University, Columbus."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0867-5227","authenticated-orcid":false,"given":"Daniel D.","family":"Kinnamon","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Internal Medicine (A.M., D.D.K., E.J., C.S., J.M., T.A., R.E.H.), The Ohio State University, Columbus."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Jordan","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Internal Medicine (A.M., D.D.K., E.J., C.S., J.M., T.A., 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