{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Pavel MA"],"funding":["NCATS NIH HHS","NHLBI NIH HHS"],"pubmed_abstract":["Rare and common genetic variants contribute to the risk of atrial fibrillation (AF). Although ion channels were among the first AF candidate genes identified, rare loss-of-function variants in structural genes, such as <i>TTN</i>, have also been implicated in AF pathogenesis, partly through the development of atrial myopathy; however, the underlying mechanisms are poorly understood. While <i>TTN</i> truncating variants (<i>TTN</i>tvs) have been causally linked to arrhythmia and cardiomyopathy syndromes, the role of missense variants (mvs) remains unclear. We show that rare <i>TTNmvs</i> are associated with worse clinical outcomes in a single-center ethnic minority clinical cohort and uncover a pathogenic mechanism by which the T32756I variant drives AF. Modeling the <i>TTN</i>-T32756I vari"],"journal":["medRxiv : the preprint server for health sciences"],"pagination":["2024.12.06.24318402"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11643245"],"repository":["biostudies-literature"],"pubmed_title":["A titin missense variant drives atrial electrical remodeling and is associated with atrial fibrillation."],"pmcid":["PMC11643245"],"funding_grant_id":["T32 HL139439","UL1 TR002003","R01 HL148444","R01 HL150586"],"pubmed_authors":["Owais A","Ornelas-Loredo A","Darbar D","Chen H","Barney M","Sandu S","DeSantiago J","Baskaran A","Al-Azzam B","Sridhar A","Darbar FA","Rehman J","Hill M","Chalazan B","Pavel MA"],"additional_accession":[]},"is_claimable":false,"name":"A titin missense variant drives atrial electrical remodeling and is associated with atrial fibrillation.","description":"Rare and common genetic variants contribute to the risk of atrial fibrillation (AF). Although ion channels were among the first AF candidate genes identified, rare loss-of-function variants in structural genes, such as <i>TTN</i>, have also been implicated in AF pathogenesis, partly through the development of atrial myopathy; however, the underlying mechanisms are poorly understood. While <i>TTN</i> truncating variants (<i>TTN</i>tvs) have been causally linked to arrhythmia and cardiomyopathy syndromes, the role of missense variants (mvs) remains unclear. We show that rare <i>TTNmvs</i> are associated with worse clinical outcomes in a single-center ethnic minority clinical cohort and uncover a pathogenic mechanism by which the T32756I variant drives AF. Modeling the <i>TTN</i>-T32756I vari","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Nov","modification":"2026-07-03T03:23:35.388Z","creation":"2025-04-04T20:27:56.757Z"},"accession":"S-EPMC11643245","cross_references":{"pubmed":["39677424"],"doi":["10.1101/2024.12.06.24318402"]}}