{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T01:32:18Z","timestamp":1793410338745,"version":"4.5.0"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"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":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease characterized by ventricular arrhythmias and progressive ventricular dysfunction. Genetic testing is recommended, and a pathogenic variant in an ARVC-associated gene is a major criterion for diagnosis according to the 2010 Task Force Criteria. As incorrect attribution of a gene to ARVC can contribute to misdiagnosis, we assembled an international multidisciplinary ARVC Clinical Genome Resource Gene Curation Expert Panel to reappraise all reported ARVC genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Following a comprehensive literature search, six 2-member teams conducted blinded independent curation of reported ARVC genes using the semiquantitative Clinical Genome Resource framework.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Of 26 reported ARVC genes, only 6 (\n                      <jats:italic>PKP2<\/jats:italic>\n                      ,\n                      <jats:italic>DSP<\/jats:italic>\n                      ,\n                      <jats:italic>DSG2<\/jats:italic>\n                      ,\n                      <jats:italic>DSC2<\/jats:italic>\n                      ,\n                      <jats:italic>JUP<\/jats:italic>\n                      , and\n                      <jats:italic>TMEM43<\/jats:italic>\n                      ) had strong evidence and were classified as definitive for ARVC causation. There was moderate evidence for 2 genes,\n                      <jats:italic>DES<\/jats:italic>\n                      and\n                      <jats:italic>PLN<\/jats:italic>\n                      . The remaining 18 genes had limited or no evidence.\n                      <jats:italic>RYR2<\/jats:italic>\n                      was refuted as an ARVC gene since clinical data and model systems exhibited a catecholaminergic polymorphic ventricular tachycardia phenotype. In ClinVar, only 5 pathogenic\/likely pathogenic variants (1.1%) in limited evidence genes had been reported in ARVC cases in contrast to 450 desmosome gene variants (97.4%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      Using the Clinical Genome Resource approach to gene-disease curation, only 8 genes (\n                      <jats:italic>PKP2<\/jats:italic>\n                      ,\n                      <jats:italic>DSP<\/jats:italic>\n                      ,\n                      <jats:italic>DSG2<\/jats:italic>\n                      ,\n                      <jats:italic>DSC2<\/jats:italic>\n                      ,\n                      <jats:italic>JUP<\/jats:italic>\n                      ,\n                      <jats:italic>TMEM43<\/jats:italic>\n                      ,\n                      <jats:italic>PLN<\/jats:italic>\n                      , and\n                      <jats:italic>DES<\/jats:italic>\n                      ) had definitive or moderate evidence for ARVC, and these genes accounted for nearly all pathogenic\/likely pathogenic ARVC variants in ClinVar. Therefore, only pathogenic\/likely pathogenic variants in these 8 genes should yield a major criterion for ARVC diagnosis. Pathogenic\/likely pathogenic variants identified in other genes in a patient should prompt further phenotyping as variants in many of these genes are associated with other cardiovascular conditions.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circgen.120.003273","type":"journal-article","created":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T17:57:52Z","timestamp":1617904672000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":236,"title":["International Evidence Based Reappraisal of Genes Associated With Arrhythmogenic Right Ventricular Cardiomyopathy Using the Clinical Genome Resource Framework"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8040-4600","authenticated-orcid":true,"given":"Cynthia A.","family":"James","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins Hospital, Baltimore, MD 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Sciences and Public Health, University of Padua, Italy (K.P., R.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5586-3418","authenticated-orcid":true,"given":"Argelia Medeiros","family":"Domingo","sequence":"additional","affiliation":[{"name":"Department for Cardiology, Inselspital, Bern University Hospital, University of Bern, Switzerland (A.M.D., B.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7870-8584","authenticated-orcid":true,"given":"Brittney","family":"Murray","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Johns Hopkins Hospital, Baltimore, MD (C.A.J., B.M., E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7489-8744","authenticated-orcid":true,"given":"Julia","family":"Cadrin-Tourigny","sequence":"additional","affiliation":[{"name":"Cardiovascular Genetics Centre, 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