@misc{10498/35838,
year = {2024},
month = {11},
url = {http://hdl.handle.net/10498/35838},
abstract = {Background/Objectives: Inherited arrhythmogenic syndromes comprise a heterogenic
group of genetic entities that lead to malignant arrhythmias and sudden cardiac death. Genetic testing
has become crucial to understand the disease etiology and allow for the early identification of relatives
at risk; however, it requires an accurate interpretation of the data to achieve a clinically actionable
outcome. This is particularly challenging for the large number of rare variants obtained by current
high-throughput techniques, which are mostly classified as of unknown significance. Methods: In
this work, we present a new algorithm for the genetic interpretation of the remaining rare variants
in order to shed light on their potential clinical implications and reduce the burden of unknown
significance. Results: Our study illustrates the potential utility of our individualized comprehensive
stepwise analyses focused on the rare variants associated with IAS, which are currently classified as
ambiguous, to further determine their trends towards pathogenicity or benign traits. Conclusions:
We advocate for personalized disease-focused population frequency data and family segregation
analyses for all rare variants that remain ambiguous to further clarify their role. The current ambiguity
should not influence medical decisions, but a potential deleterious role would suggest a closer clinical
follow-up and frequent genetic data review for a more personalized clinical approach.},
publisher = {MDPI},
keywords = {sudden cardiac death},
keywords = {inherited arrhythmogenic syndromes},
keywords = {genetics},
keywords = {clinical interpretation},
keywords = {variants of unknown significance},
title = {Actionable Variants of Unknown Significance in Inherited Arrhythmogenic Syndromes: A Further Step Forward in Genetic Diagnosis},
doi = {10.3390/biomedicines12112553},
author = {Martínez  Barrios, Estefanía and Greco, Andrea and Cruzalegui, José and Cesar, Sergi and Díez Escuté, Nuria and Cerralbo, Patricia and Chipa, Fredy and Zschaeck, Irene and Fogaça-da-Mata, Miguel and Diez López, Carles and Arbelo, Elena and Grassi, Simone and Oliva, Antonio and Toro Cebada, Rocío and Sarquella Brugada, Georgia and Campuzano, Oscar},
}