TTN:c.12478del in proximal I-band of titin represents a common molecular cause of dilated cardiomyopathy in Slovenian patients

• DOI: 10.1186/s13023-025-03613-7
• Publication Date: 2025-02-28T13:15:18Z
• Authors: Nina Vodnjov; Andraž Cerar; Aleš Maver; Borut Peterlin; Karin Writzl
• Keywords: Dilated Cardiomyopathy; Proband

Abstract Background Titin truncating variants ( TTN tv-s) are the most common genetic cause of dilated cardiomyopathy (DCM). Only rare tv-s in constitutively expressed exons A-band protein titin associated with DCM according to guidelines, however, studies large cohorts patients suggest that region where is wider, extending at least into I-band. The aim this study was describe molecular pathology Slovenian and clinically characterise recurrent tv. Results We collected all identified using next-generation sequencing testing between 2010 July 2024, resulting 42 unique 54 patients. :c.12478del variant, affecting not but proximal I-band, specifically cardiac-specific N2Bus region, found be present seven (11.6%) probands DCM. Genetic characterisation revealed a probable founder origin variant. Clinical these phenotype consistent severely reduced left ventricular ejection fraction probands. Three (43%) had atrial fibrillation and/or non-sustained tachycardia. Based on literature reports evidence supporting pathogenicity variant we classified I-band as (likely) pathogenic. Therefore, 33 (78.6%) were pathogenic (13 19 20 25 probands), meaning 44 genotype-positive DCM, explaining 73.3% Conclusion report an almost threefold higher diagnostic yield compared previously reported findings from other populations. also highlight need for screening geographical region.