{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T04:06:22Z","timestamp":1749787582806,"version":"3.41.0"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cardiovasc electrophysiol"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>SCN5A<\/jats:italic> is the most common susceptibility gene in patients with Brugada syndrome (BrS); however, the interpretation and management of benign or variants of unknown clinical significance (VUS) in <jats:italic>SCN5A<\/jats:italic> remains a challenge despite the availability of genetic testing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to investigate the relationship between the <jats:italic>SCN5A<\/jats:italic> variants and clinical symptoms of BrS patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We resequenced the <jats:italic>SCN5A<\/jats:italic> gene in 239 patients diagnosed with BrS at Hiroshima University Hospital and analyzed the association between the <jats:italic>SCN5A<\/jats:italic> variants and clinical features, 12\u2010lead electrocardiography (ECG) parameters, and signal\u2010averaged ECG.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, 84 <jats:italic>SCN5A<\/jats:italic> variants were identified: 55 benign, 7 pathogenic, and 22 VUS. No significant difference in the incidence of previous cardiac events was observed between patients with and without <jats:italic>SCA5A<\/jats:italic> benign variants. The female proportion was higher in BrS patients with <jats:italic>SCN5A<\/jats:italic> VUS or pathogenic variants. Moreover, the symptomatic proportion was higher in BrS patients with <jats:italic>SCN5A<\/jats:italic> VUS or pathogenic variants than in those without <jats:italic>SCN5A<\/jats:italic> variants. Multivariate analyses revealed that the presence of <jats:italic>SCN5A<\/jats:italic> pathogenic variants, longer r\u2010J intervals in lead V1, and the presence of fragmented QRS were independently associated with cardiac events in BrS patients, and that positive late potentials, longer LAS40, and lower RMS40 were significantly associated with symptomatic BrS in patients carrying <jats:italic>SCN5A<\/jats:italic> VUS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:italic>SCN5A<\/jats:italic> pathogenic variants were found to be independent risk factors for cardiac events in BrS patients. Although <jats:italic>SCN5A<\/jats:italic> VUS was not an independent risk factor for cardiac events, proportion of symptomatic patients was higher in BrS patients with <jats:italic>SCN5A<\/jats:italic> VUS than in those without <jats:italic>SCN5A<\/jats:italic> variants. In BrS patients with <jats:italic>SCN5A<\/jats:italic> VUS, the signal\u2010averaged ECG was the key to the risk stratification for cardiac events.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jce.16643","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T01:50:13Z","timestamp":1742867413000},"page":"1223-1233","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Features of Brugada Syndrome Patients With <i>SCN5A<\/i> Variants"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9512-9506","authenticated-orcid":false,"given":"Sho","family":"Okamura","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine Graduate School of Biomedical and Health Sciences, Hiroshima University Hiroshima 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