@misc{10498/23066,
year = {2020},
month = {4},
url = {http://hdl.handle.net/10498/23066},
abstract = {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.},
publisher = {ELSEVIER},
keywords = {Sudden cardiac death},
keywords = {Arrhythmias},
keywords = {Pathogenicity},
keywords = {Genetics},
title = {Reanalysis and reclassification of rare genetic variants associated with inherited arrhythmogenic syndromes},
doi = {10.1016/j.ebiom.2020.102732},
author = {Campuzano, Oscar and Sarquella-Brugada, Georgia and Fernandez-Falgueras, Anna and Coll, Mónica and Iglesias, Anna and Ferrer-Costa, Carles and Cesar, Sergi and Arbelo, Elena and García- Alvarez, Ana and Jordà, Paloma and Toro Cebada, Rocío and Tiron de Llano, Coloma and Grassi, Simone and Oliva, Antonio and Brugada, Josep and Brugada, Ramón},
}