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Data on the clinical course of <jats:italic>FLNC<\/jats:italic>\u2010related HCM are conflicting with some studies suggesting mild phenotypes whereas other studies have reported more severe outcomes. In this study, we present a novel <jats:italic>FLNC<\/jats:italic> variant (Ile1937Asn) that was identified in a large family of French\u2010Canadian descent with excellent segregation data. <jats:italic>FLNC<\/jats:italic>\u2010Ile1937Asn is a novel missense variant characterized by full penetrance and poor clinical outcomes. End stage heart failure requiring transplantation occurred in 43% and sudden cardiac death in 29% of affected family members. Other particular features of <jats:italic>FLNC\u2010<\/jats:italic>Ile1937Asn include an early disease onset (mean age of 19\u2009years) and the development of a marked atrial myopathy (severe biatrial dilatation with remodeling and multiple complex atrial arrhythmias) that was present in all gene carriers. The FLNC\u2010Ile1937Asn variant is a novel, pathogenic mutation resulting in a severe form of HCM with full disease penetrance. The variant is associated with a high proportion of end\u2010stage heart failure, heart transplantation, and disease\u2010related mortality. Close follow\u2010up and appropriate risk stratification of affected individuals at specialized heart centers is recommended.<\/jats:p>","DOI":"10.1002\/ajmg.a.63169","type":"journal-article","created":{"date-parts":[[2023,3,3]],"date-time":"2023-03-03T07:11:45Z","timestamp":1677827505000},"page":"1508-1517","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Novel filamin C (<i>FLNC<\/i>) variant causes a severe form of familial mixed <scp>hypertrophic\u2010restrictive<\/scp> cardiomyopathy"],"prefix":"10.1002","volume":"191","author":[{"given":"Nathalie","family":"Gaudreault","sequence":"first","affiliation":[{"name":"Centre de Recherche de l'Institut universitaire de cardiologie et de pneumologie de Qu\u00e9bec Laval University  Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis\u2010Jacques","family":"Ruel","sequence":"additional","affiliation":[{"name":"Centre de Recherche de 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