@article{ref1,
title="Reevaluation of ambiguous genetic variants in sudden unexplained deaths of a young cohort",
journal="International journal of legal medicine",
year="2023",
author="Martinez-Barrios, Estefanía and Sarquella-Brugada, Georgia and Perez-Serra, Alexandra and Fernandez-Falgueras, Anna and Cesar, Sergi and Alcalde, Mireia and Coll, Monica and Puigmulé, Marta and Iglesias, Anna and Ferrer-Costa, Carles and Del Olmo, Bernat and Picó, Ferran and López, Laura and Fiol, Victoria and Cruzalegui, José and Hernandez, Clara and Arbelo, Elena and Díez-Escuté, Nuria and Cerralbo, Patricia and Grassi, Simone and Oliva, Antonio and Toro, Rocío and Brugada, Josep and Brugada, Ramon and Campuzano, Oscar",
volume="ePub",
number="ePub",
pages="ePub-ePub",
abstract="Sudden death cases in the young population remain without a conclusive cause of decease in almost 40% of cases. In these situations, cardiac arrhythmia of genetic origin is suspected as the most plausible cause of death. Molecular autopsy may reveal a genetic defect in up to 20% of families. Most than 80% of rare variants remain classified with an ambiguous role, impeding a useful clinical translation. Our aim was to update rare variants originally classified as of unknown significance to clarify their role. Our cohort included fifty-one post-mortem samples of young cases who died suddenly and without a definite cause of death. Five years ago, molecular autopsy identified at least one rare genetic alteration classified then as ambiguous following the American College of Medical Genetics and Genomics' recommendations. We have reclassified the same rare variants including novel data. About 10% of ambiguous variants change to benign/likely benign mainly because of improved population frequencies. Excluding cases who died before one year of age, almost 21% of rare ambiguous variants change to benign/likely benign. This fact makes it important to discard these rare variants as a cause of sudden unexplained death, avoiding anxiety in relatives' carriers. Twenty-five percent of the remaining variants show a tendency to suspicious deleterious role, highlighting clinical follow-up of carriers. Periodical reclassification of rare variants originally classified as ambiguous is crucial, at least updating frequencies every 5 years. This action aids to increase accuracy to enable and conclude a cause of death as well as translation into the clinic.<p /> <p>Language: en</p>",
language="en",
issn="0937-9827",
doi="10.1007/s00414-023-02951-0",
url="http://dx.doi.org/10.1007/s00414-023-02951-0"
}