{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T13:41:18Z","timestamp":1792158078865,"version":"4.4.0"},"reference-count":32,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"am","delay-in-days":363,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":["clinicalkey.fr","clinicalkey.jp","clinicalkey.es","clinicalkey.com.au","heartrhythmjournal.com","clinicalkey.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Heart Rhythm"],"published-print":{"date-parts":[[2025,3]]},"DOI":"10.1016\/j.hrthm.2024.08.018","type":"journal-article","created":{"date-parts":[[2024,8,10]],"date-time":"2024-08-10T15:54:36Z","timestamp":1723305276000},"page":"844-851","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":16,"title":["Systematic analysis of SCN5A variants associated with inherited cardiac diseases"],"prefix":"10.1016","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2392-3759","authenticated-orcid":false,"given":"Alexis","family":"Hermida","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Jedraszak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavie","family":"Ader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Denjoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Fressart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillipe","family":"Maury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Beyls","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrien","family":"Bloch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga\u00ebl","family":"Clerici","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"Daire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Defaye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Dupin-Deguine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loic","family":"Gar\u00e7on","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Klug","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Ginglinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Sylvain","family":"Hermida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Jesel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diala","family":"Khraiche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Kubala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Lacotte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikael","family":"Laredo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Leenhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Le Guillou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francois","family":"Lesaffre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Maltret","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Magnin-Poull","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eloi","family":"Marijon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Nambot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Neyroud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandro","family":"Ninni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lien","family":"Palmyre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Luc","family":"Pasquie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Proukhnitzky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Reant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Richard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Rollin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Rooryck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Sacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"Schaefer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agathe","family":"Vernier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre-Fran\u00e7ois","family":"Winum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Wahbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Waintraub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Waldmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sacha","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Zouaghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Charron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Extramiana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estelle","family":"Gandjbakhch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.hrthm.2024.08.018_bib1","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCGEN.121.003432","article-title":"Arrhythmic phenotypes are a defining feature of dilated cardiomyopathy\u2013associated SCN5A variants: a systematic review","volume":"15","author":"Peters","year":"2022","journal-title":"Circ Genom Precis Med"},{"key":"10.1016\/j.hrthm.2024.08.018_bib2","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.hrthm.2009.09.069","article-title":"An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing","volume":"7","author":"Kapplinger","year":"2010","journal-title":"Heart Rhythm"},{"key":"10.1016\/j.hrthm.2024.08.018_bib3","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.3389\/fphys.2018.01372","article-title":"SCN5A variants: association with cardiac disorders","volume":"9","author":"Li","year":"2018","journal-title":"Front Physiol"},{"key":"10.1016\/j.hrthm.2024.08.018_bib4","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.pbiomolbio.2008.10.005","article-title":"SCN5A channelopathies\u2014an update on mutations and mechanisms","volume":"98","author":"Zimmer","year":"2008","journal-title":"Prog Biophys Mol Biol"},{"key":"10.1016\/j.hrthm.2024.08.018_bib5","article-title":"Structure of human Nav1.5 reveals the fast inactivation\u2013related segments as a mutational hotspot for the long QT syndrome","volume":"118","author":"Li","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.hrthm.2024.08.018_bib6","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s41436-020-00946-5","article-title":"Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls","volume":"23","author":"Walsh","year":"2021","journal-title":"Genet Med"},{"key":"10.1016\/j.hrthm.2024.08.018_bib7","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.hrthm.2005.01.020","article-title":"Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing","volume":"2","author":"Tester","year":"2005","journal-title":"Heart Rhythm"},{"key":"10.1016\/j.hrthm.2024.08.018_bib8","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1016\/j.hrthm.2009.05.021","article-title":"Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test","volume":"6","author":"Kapplinger","year":"2009","journal-title":"Heart Rhythm"},{"key":"10.1016\/j.hrthm.2024.08.018_bib9","first-page":"54","article-title":"A novel functional variant residing outside the SCN5A-encoded Nav1.5 voltage-sensing domain causes multifocal ectopic Purkinje-related premature contractions","volume":"8","author":"Gao","year":"2022","journal-title":"Heart Rhythm Case Rep"},{"key":"10.1016\/j.hrthm.2024.08.018_bib10","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1161\/01.RES.85.12.1206","article-title":"A single Na+ channel mutation causing both long-QT and Brugada syndromes","volume":"85","author":"Bezzina","year":"1999","journal-title":"Circ Res"},{"key":"10.1016\/j.hrthm.2024.08.018_bib11","doi-asserted-by":"crossref","first-page":"3081","DOI":"10.1161\/hc5001.100834","article-title":"Novel SCN5A mutation leading either to isolated cardiac conduction defect or Brugada syndrome in a large French family","volume":"104","author":"Kyndt","year":"2001","journal-title":"Circulation"},{"key":"10.1016\/j.hrthm.2024.08.018_bib12","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1172\/JCI0215570","article-title":"Long QT syndrome, Brugada syndrome, and conduction system disease are linked to a single sodium channel mutation","volume":"110","author":"Grant","year":"2002","journal-title":"J Clin Invest"},{"key":"10.1016\/j.hrthm.2024.08.018_bib13","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.hrthm.2010.10.005","article-title":"Pleiotropic mutations in ion channels: what lies behind them?","volume":"8","author":"Crotti","year":"2011","journal-title":"Heart Rhythm"},{"key":"10.1016\/j.hrthm.2024.08.018_bib14","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/12618","article-title":"Cardiac conduction defects associate with mutations in SCN5A","volume":"23","author":"Schott","year":"1999","journal-title":"Nat Genet"},{"key":"10.1016\/j.hrthm.2024.08.018_bib15","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/S0735-1097(02)02864-4","article-title":"Haploinsufficiency in combination with aging causes SCN5A-linked hereditary Len\u00e8gre disease","volume":"41","author":"Probst","year":"2003","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.hrthm.2024.08.018_bib16","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1161\/01.RES.0000052672.97759.36","article-title":"Compound heterozygosity for mutations (W156X and R225W) in SCN5A associated with severe cardiac conduction disturbances and degenerative changes in the conduction system","volume":"92","author":"Bezzina","year":"2003","journal-title":"Circ Res"},{"key":"10.1016\/j.hrthm.2024.08.018_bib17","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1172\/JCI200318062","article-title":"Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A)","volume":"112","author":"Benson","year":"2003","journal-title":"J Clin Invest"},{"key":"10.1016\/j.hrthm.2024.08.018_bib18","doi-asserted-by":"crossref","first-page":"3078","DOI":"10.1016\/j.ijcard.2012.11.062","article-title":"Autosomal recessive paediatric sick sinus syndrome associated with novel compound mutations in SCN5A","volume":"167","author":"Kodama","year":"2013","journal-title":"Int J Cardiol"},{"key":"10.1016\/j.hrthm.2024.08.018_bib19","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1161\/01.RES.0000050585.07097.D7","article-title":"A cardiac sodium channel mutation cosegregates with a rare connexin40 genotype in familial atrial standstill","volume":"92","author":"Groenewegen","year":"2003","journal-title":"Circ Res"},{"key":"10.1016\/j.hrthm.2024.08.018_bib20","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1161\/01.CIR.102.9.945","article-title":"The elusive link between LQT3 and Brugada syndrome: the role of flecainide challenge","volume":"102","author":"Priori","year":"2000","journal-title":"Circulation"},{"key":"10.1016\/j.hrthm.2024.08.018_bib21","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.joa.2016.05.007","article-title":"Cardiac conduction defects and Brugada syndrome: a family with overlap syndrome carrying a nonsense SCN5A mutation","volume":"33","author":"Aoki","year":"2017","journal-title":"J Arrhythm"},{"key":"10.1016\/j.hrthm.2024.08.018_bib22","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1111\/j.1540-8167.2006.00349.x","article-title":"Progressive cardiac conduction defect is the prevailing phenotype in carriers of a Brugada syndrome SCN5A mutation","volume":"17","author":"Probst","year":"2006","journal-title":"J Cardiovasc Electrophysiol"},{"key":"10.1016\/j.hrthm.2024.08.018_bib23","first-page":"2219","article-title":"The E1784K mutation in SCN5A is associated with mixed clinical phenotype of type 3 long QT syndrome","volume":"118","author":"Makita","year":"2008","journal-title":"J Clin Invest"},{"key":"10.1016\/j.hrthm.2024.08.018_bib24","doi-asserted-by":"crossref","first-page":"E91","DOI":"10.1161\/01.RES.86.9.e91","article-title":"Two distinct congenital arrhythmias evoked by a multidysfunctional Na+ channel","volume":"86","author":"Veldkamp","year":"2000","journal-title":"Circ Res"},{"key":"10.1016\/j.hrthm.2024.08.018_bib25","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/j.hrthm.2022.03.1223","article-title":"SCN5A overlap syndromes: an open-minded approach","volume":"19","author":"Porretta","year":"2022","journal-title":"Heart Rhythm"},{"key":"10.1016\/j.hrthm.2024.08.018_bib26","doi-asserted-by":"crossref","first-page":"H1822","DOI":"10.1152\/ajpheart.00101.2006","article-title":"Partial expression defect for the SCN5A missense mutation G1406R depends on splice variant background Q1077 and rescue by mexiletine","volume":"291","author":"Tan","year":"2006","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"10.1016\/j.hrthm.2024.08.018_bib27","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1016\/j.hrthm.2018.03.033","article-title":"Copy number variations of SCN5A in Brugada syndrome","volume":"15","author":"Sonoda","year":"2018","journal-title":"Heart Rhythm"},{"key":"10.1016\/j.hrthm.2024.08.018_bib28","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.jacc.2005.03.066","article-title":"Developmental aspects of long QT syndrome type 3 and Brugada syndrome on the basis of a single SCN5A mutation in childhood","volume":"46","author":"Beaufort-Krol","year":"2005","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.hrthm.2024.08.018_bib29","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1161\/CIRCULATIONAHA.105.549071","article-title":"KCNH2-K897T is a genetic modifier of latent congenital long-QT syndrome","volume":"112","author":"Crotti","year":"2005","journal-title":"Circulation"},{"key":"10.1016\/j.hrthm.2024.08.018_bib30","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1161\/CIRCULATIONAHA.105.601294","article-title":"SCN5A polymorphism restores trafficking of a Brugada syndrome mutation on a separate gene","volume":"114","author":"Poelzing","year":"2006","journal-title":"Circulation"},{"key":"10.1016\/j.hrthm.2024.08.018_bib31","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.ijcard.2017.05.099","article-title":"Value of the sodium-channel blocker challenge in Brugada syndrome","volume":"245","author":"Therasse","year":"2017","journal-title":"Int J Cardiol"},{"key":"10.1016\/j.hrthm.2024.08.018_bib32","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.ijcard.2017.09.010","article-title":"SCN5A mutation type and topology are associated with the risk of ventricular arrhythmia by sodium channel blockers","volume":"266","author":"Amin","year":"2018","journal-title":"Int J Cardiol"}],"container-title":["Heart Rhythm"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1547527124031369?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1547527124031369?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T12:19:33Z","timestamp":1740658773000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1547527124031369"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3]]},"references-count":32,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["S1547527124031369"],"URL":"https:\/\/doi.org\/10.1016\/j.hrthm.2024.08.018","relation":{},"ISSN":["1547-5271"],"issn-type":[{"value":"1547-5271","type":"print"}],"subject":[],"published":{"date-parts":[[2025,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Systematic analysis of SCN5A variants associated with inherited cardiac diseases","name":"articletitle","label":"Article Title"},{"value":"Heart Rhythm","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.hrthm.2024.08.018","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 Heart Rhythm Society. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}]}}