Rare Variants Associated with Arrhythmogenic Cardiomyopathy: Reclassification Five Years Later

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...

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Detalles Bibliográficos
Autores: Vallverdú-Prats, Marta, Alcalde Masegu, Mireia, Sarquella Brugada, Geòrgia, Cesar, Sergi, Arbelo, Elena, Fernández-Falgueras, Anna, Coll Vidal, Mònica, Perez-Serra, Alexandra, Puigmulé, Marta, Iglesias, Anna, Fiol, Victoria, Ferrer Costa, Carles, Olmo, Bernat del, Picó, Ferran, López López, Laura, Jordà, Paloma, García Álvarez, Ana, Tirón de Llano, Coloma, Toro, Rocío, Grassi, Simone, Oliva, Antonio, Brugada Terradellas, Josep, Brugada, Ramon, Campuzano Larrea, Oscar
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10256/19223
Acceso en línea:http://hdl.handle.net/10256/19223
Access Level:acceso abierto
Palabra clave:Mort sobtada
Sudden death
Miocardi -- Malalties
Myocardium -- Diseases
Arrítmia
Arrhythmia
Cor -- Malalties -- Aspectes genètics
Heart -- Diseases -- Genetic aspects
Descripción
Sumario: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

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