{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T19:55:56Z","timestamp":1791575756300,"version":"4.3.4"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T00:00:00Z","timestamp":1625529600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2021,7,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Each of the cardiomyopathies, classically categorized as hypertrophic cardiomyopathy, dilated cardiomyopathy (DCM), and arrhythmogenic right ventricular cardiomyopathy, has a signature genetic theme. Hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy are largely understood as genetic diseases of sarcomere or desmosome proteins, respectively. In contrast, &gt;250 genes spanning &gt;10 gene ontologies have been implicated in DCM, representing a complex and diverse genetic architecture. To clarify this, a systematic curation of evidence to establish the relationship of genes with DCM was conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>An international panel with clinical and scientific expertise in DCM genetics evaluated evidence supporting monogenic relationships of genes with idiopathic DCM. The panel used the Clinical Genome Resource semiquantitative gene-disease clinical validity classification framework with modifications for DCM genetics to classify genes into categories on the basis of the strength of currently available evidence. Representation of DCM genes on clinically available genetic testing panels was evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Fifty-one genes with human genetic evidence were curated. Twelve genes (23%) from 8 gene ontologies were classified as having definitive (\n                      <jats:italic>BAG3<\/jats:italic>\n                      ,\n                      <jats:italic>DES<\/jats:italic>\n                      ,\n                      <jats:italic>FLNC<\/jats:italic>\n                      ,\n                      <jats:italic>LMNA<\/jats:italic>\n                      ,\n                      <jats:italic>MYH7<\/jats:italic>\n                      ,\n                      <jats:italic>PLN<\/jats:italic>\n                      ,\n                      <jats:italic>RBM20<\/jats:italic>\n                      ,\n                      <jats:italic>SCN5A<\/jats:italic>\n                      ,\n                      <jats:italic>TNNC1<\/jats:italic>\n                      ,\n                      <jats:italic>TNNT2<\/jats:italic>\n                      ,\n                      <jats:italic>TTN<\/jats:italic>\n                      ) or strong (\n                      <jats:italic>DSP<\/jats:italic>\n                      ) evidence. Seven genes (14%;\n                      <jats:italic>ACTC1<\/jats:italic>\n                      ,\n                      <jats:italic>ACTN2<\/jats:italic>\n                      ,\n                      <jats:italic>JPH2<\/jats:italic>\n                      ,\n                      <jats:italic>NEXN<\/jats:italic>\n                      ,\n                      <jats:italic>TNNI3<\/jats:italic>\n                      ,\n                      <jats:italic>TPM1<\/jats:italic>\n                      ,\n                      <jats:italic>VCL<\/jats:italic>\n                      ) including 2 additional ontologies were classified as moderate evidence; these genes are likely to emerge as strong or definitive with additional evidence. Of these 19 genes, 6 were similarly classified for hypertrophic cardiomyopathy and 3 for arrhythmogenic right ventricular cardiomyopathy. Of the remaining 32 genes (63%), 25 (49%) had limited evidence, 4 (8%) were disputed, 2 (4%) had no disease relationship, and 1 (2%) was supported by animal model data only. Of the 16 evaluated clinical genetic testing panels, most definitive genes were included, but panels also included numerous genes with minimal human evidence.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>In the curation of 51 genes, 19 had high evidence (12 definitive\/strong, 7 moderate). It is notable that these 19 genes explain only a minority of cases, leaving the remainder of DCM genetic architecture incompletely addressed. Clinical genetic testing panels include most high-evidence genes; however, genes lacking robust evidence are also commonly included. We recommend that high-evidence DCM genes be used for clinical practice and that caution be exercised in the interpretation of variants in variable-evidence DCM genes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.120.053033","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T05:01:03Z","timestamp":1620190863000},"page":"7-19","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":512,"title":["Evidence-Based Assessment of Genes in Dilated Cardiomyopathy"],"prefix":"10.1161","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2073-3258","authenticated-orcid":true,"given":"Elizabeth","family":"Jordan","sequence":"first","affiliation":[{"name":"Division of Human Genetics (E.J., L.P., T.A., R.E.H.), Department of Internal Medicine, Wexner Medical Center, The Ohio State University, Columbus."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laiken","family":"Peterson","sequence":"additional","affiliation":[{"name":"Division of Human Genetics (E.J., L.P., T.A., R.E.H.), Department of Internal Medicine, Wexner Medical Center, The Ohio State University, Columbus."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0376-0227","authenticated-orcid":true,"given":"Tomohiko","family":"Ai","sequence":"additional","affiliation":[{"name":"Division of Human Genetics (E.J., L.P., T.A., R.E.H.), Department of Internal Medicine, Wexner Medical Center, The Ohio State University, Columbus."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0050-5717","authenticated-orcid":true,"given":"Babken","family":"Asatryan","sequence":"additional","affiliation":[{"name":"Department for Cardiology, Inselspital, Bern University Hospital, University of Bern, Switzerland (B.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Bronicki","sequence":"additional","affiliation":[{"name":"Department of Genetics, Children\u2019s Hospital of Eastern Ontario, Ottawa, Canada (L.B., O.J.)."},{"name":"Department of Laboratory and Pathology Medicine, University of Ottawa, Ontario, Canada (L.B., O.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Brown","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD (E.B., C.A.J., B.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9047-9032","authenticated-orcid":true,"given":"Rudy","family":"Celeghin","sequence":"additional","affiliation":[{"name":"Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padua, Italy (R.C., K.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Edwards","sequence":"additional","affiliation":[{"name":"Clinical Genetics and Genomics Laboratory, Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom (M.E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, Los Angeles (J.F., J. Wang)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4846-7676","authenticated-orcid":true,"given":"Jodie","family":"Ingles","sequence":"additional","affiliation":[{"name":"Cardio Genomics Program at Centenary Institute, University of Sydney, Australia (J.I.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8040-4600","authenticated-orcid":true,"given":"Cynthia A.","family":"James","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD (E.B., C.A.J., B.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Jarinova","sequence":"additional","affiliation":[{"name":"Department of Genetics, Children\u2019s Hospital of Eastern Ontario, Ottawa, Canada (L.B., O.J.)."},{"name":"Department of Laboratory and Pathology Medicine, University of Ottawa, Ontario, Canada (L.B., O.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8979-2096","authenticated-orcid":true,"given":"Renee","family":"Johnson","sequence":"additional","affiliation":[{"name":"Victor Chang Cardiac Research Institute, Sydney, Australia (R.J.)."},{"name":"Department of Medicine, University of New South Wales, Sydney, Australia (R.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3407-0248","authenticated-orcid":true,"given":"Daniel P.","family":"Judge","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston (D.P.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1753-452X","authenticated-orcid":true,"given":"Najim","family":"Lahrouchi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Cardiology, Heart Centre, Amsterdam Cardiovascular Sciences, Amsterdam Universitair Medische Centra, University of Amsterdam, the Netherlands (N.L., R.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4687-0186","authenticated-orcid":true,"given":"Ronald H.","family":"Lekanne Deprez","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Amsterdam University Medical Center location Academic Medical Center, the Netherlands (R.H.L.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9077-4741","authenticated-orcid":true,"given":"R. Thomas","family":"Lumbers","sequence":"additional","affiliation":[{"name":"Institute of Health Informatics, University College London, London, UK (R.T.L.)."},{"name":"Health Data Research UK London, University College London, UK (R.T.L.)."},{"name":"University College London British Heart Foundation Research Accelerator, London, United Kingdom (R.T.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Mazzarotto","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center, Royal Brompton and Harefield Hospitals, National Health Service Foundation Trust, London, United Kingdom (F.M., J. Ware)."},{"name":"National Heart and Lung Institute, Imperial College London, United Kingdom (F.M., J. Ware)."},{"name":"Department of Clinical and Experimental Medicine, University of Florence, Italy (F.M.)."},{"name":"Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy (F.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5586-3418","authenticated-orcid":true,"given":"Argelia","family":"Medeiros Domingo","sequence":"additional","affiliation":[{"name":"Swiss DNAlysis Cardiogenetics, D\u00fcbendorf, Switzerland (A.M.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca L.","family":"Miller","sequence":"additional","affiliation":[{"name":"Cardiovascular Genomics Center, Inova Heart and Vascular Institute, Falls Church, VA (R.L.M., P. 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