RT journal article
T1 Rare Variants Associated with Arrhythmogenic Cardiomyopathy: Reclassification Five Years Later.
A1 Vallverdú-Prats, Marta
A1 Alcalde, Mireia
A1 Sarquella-Brugada, Georgia
A1 Cesar, Sergi
A1 Arbelo, Elena
A1 Fernandez-Falgueras, Anna
A1 Coll, Mónica
A1 Perez-Serra, Alexandra
A1 Puigmulé, Marta
A1 Iglesias, Anna
A1 Fiol, Victoria
A1 Ferrer-Costa, Carles
A1 del Olmo, Bernat
A1 Picó, Ferran
A1 Lopez, Laura
A1 Jordà, Paloma
A1 García-Álvarez, Ana
A1 Tiron de Llano, Coloma
A1 Toro Cebada, Rocío
A1 Grassi, Simone
A1 Oliva, Antonio
A1 Brugada, Josep
A1 Brugada, Ramón
A1 Campuzano, Oscar
A2 Medicina
K1 sudden cardiac death
K1 arrhythmogenic cardiomyopathy
K1 genetics
K1 rare variants
K1 reclassification
AB Genetic interpretation of rare variants associated with arrhythmogenic cardiomyopathy (ACM) is essential due to their diagnostic implications. New data may relabel previous variant classifications, but how often reanalysis is necessary remains undefined. Five years ago, 39 rare ACM-related variants were identified in patients with features of cardiomyopathy. These variants were classified following the American College of Medical Genetics and Genomics' guidelines. In the present study, we reevaluated these rare variants including novel available data. All cases carried one rare variant classified as being of ambiguous significance (82.05%) or likely pathogenic (17.95%) in 2016. In our comprehensive reanalysis, the classification of 30.77% of these variants changed, mainly due to updated global frequencies. As in 2016, nowadays most variants were classified as having an uncertain role (64.1%), but the proportion of variants with an uncertain role was significantly decreased (17.95%). The percentage of rare variants classified as potentially deleterious increased from 17.95% to 23.07%. Moreover, 83.33% of reclassified variants gained certainty. We propose that periodic genetic reanalysis of all rare variants associated with arrhythmogenic cardiomyopathy should be undertaken at least once every five years. Defining the roles of rare variants may help clinicians obtain a definite diagnosis.
PB MDPI
SN 2075-4426
YR 2021
FD 2021-02
LK http://hdl.handle.net/10498/26336
UL http://hdl.handle.net/10498/26336
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 13-nov-2026