RT journal article
T1 Reanalysis and reclassification of rare genetic variants associated with inherited arrhythmogenic syndromes
A1 Campuzano, Oscar
A1 Sarquella-Brugada, Georgia
A1 Fernandez-Falgueras, Anna
A1 Coll, Mónica
A1 Iglesias, Anna
A1 Ferrer-Costa, Carles
A1 Cesar, Sergi
A1 Arbelo, Elena
A1 García- Alvarez, Ana
A1 Jordà, Paloma
A1 Toro Cebada, Rocío
A1 Tiron de Llano, Coloma
A1 Grassi, Simone
A1 Oliva, Antonio
A1 Brugada, Josep
A1 Brugada, Ramón
A2 Medicina
K1 Sudden cardiac death
K1 Arrhythmias
K1 Pathogenicity
K1 Genetics
AB Background: Accurate interpretation of rare genetic variants is a challenge for clinical translation. Updates in recommendations for rare variant classification require the reanalysis and reclassification. We aim to perform an exhaustive re-analysis of rare variants associated with inherited arrhythmogenic syndromes, which were classified ten years ago, to determine whether their classification aligns with current standards and research findings.Methods: In 2010, the rare variants identified through genetic analysis were classified following recommendations available at that time. Nowadays, the same variants have been reclassified following current American College of Medical Genetics and Genomics recommendations.Findings: Our cohort included 104 cases diagnosed with inherited arrhythmogenic syndromes and 17 post-mortem cases in which inherited arrhythmogenic syndromes was cause of death. 71.87% of variants change their classification. While 65.62% of variants were classified as likely pathogenic in 2010, after reanalysis, only 17.96% remain as likely pathogenic. In 2010, 18.75% of variants were classified as uncertain role but nowadays 60.15% of variants are classified of unknown significance.Interpretation: Reclassification occurred in more than 70% of rare variants associated with inherited arrhythmogenic syndromes. Our results support the periodical reclassification and personalized clinical translation of rare variants to improve diagnosis and adjust treatment.
PB ELSEVIER
SN 2352-3964
YR 2020
FD 2020-04
LK http://hdl.handle.net/10498/23066
UL http://hdl.handle.net/10498/23066
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 13-nov-2026