RT journal article
T1 Implementing a New Algorithm for Reinterpretation of Ambiguous Variants in Genetic Dilated Cardiomyopathy
A1 Pérez Serra, Alexandra
A1 Toro Cebada, Rocío
A1 Martínez Barrios, Estefanía
A1 Iglesias, Anna
A1 Fernández Falgueras, Anna
A1 Alcalde, Mireia
A1 Coll, Mónica
A1 Puigmulé, Marta
A1 del Olmo, Bernat
A1 Picó, Ferran
A1 López, Laura
A1 Arbelo, Elena
A1 César, Sergi
A1 Tirón de Llano, Coloma
A1 Mangas Rojas, Alipio
A1 Brugada, Josep
A1 Sarquella Brugada, Georgia
A1 Brugada, Ramón
A1 Campuzano, Oscar
A2 Medicina
K1 sudden cardiac death
K1 dilated cardiomyopathy
K1 genetics
K1 interpretation
AB Dilated cardiomyopathy is a heterogeneous entity that leads to heart failure and malignantarrhythmias. Nearly 50% of cases are inherited; therefore, genetic analysis is crucial to unravel thecause and for the early identification of carriers at risk. A large number of variants remain classifiedas ambiguous, impeding an actionable clinical translation. Our goal was to perform a comprehensiveupdate of variants previously classified with an ambiguous role, applying a new algorithm of alreadyavailable tools. In a cohort of 65 cases diagnosed with dilated cardiomyopathy, a total of 125 geneticvariants were classified as ambiguous. Our reanalysis resulted in the reclassification of 12% of variantsfrom an unknown to likely benign or likely pathogenic role, due to improved population frequencies.For all the remaining ambiguous variants, we used our algorithm; 60.9% showed a potential but notconfirmed deleterious role, and 24.5% showed a potential benign role. Periodically updating thepopulation frequencies is a cheap and fast action, making it possible to clarify the role of ambiguousvariants. Here, we performa comprehensive reanalysis to help to clarify the role of most of ambiguousvariants. Our specific algorithms facilitate genetic interpretation in dilated cardiomyopathy.
PB MDPI
SN 1422-0067
YR 2024
FD 2024
LK http://hdl.handle.net/10498/33546
UL http://hdl.handle.net/10498/33546
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 07-nov-2026