Rare Variants Associated with Arrhythmogenic Cardiomyopathy: Reclassification Five Years Later
Por:
Vallverdú-Prats M, Alcalde M, Sarquella-Brugada G, César-Díaz S, Arbelo E, Fernandez-Falgueras A, Coll M, Pérez-Serra A, Puigmulé M, Iglesias A, Fiol JV, Ferrer-Costa C, Olmo BD, Picó F, Lopez L, Jordà P, García-Álvarez A, Llano CT, Toro R, Grassi S, Oliva A, Brugada-Terradellas J, Brugada R and Campuzano O
Publicada:
1 mar 2021
Ahead of Print:
26 feb 2021
Categoría:
Medicine (miscellaneous)
Resumen:
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.
Filiaciones:
Vallverdú-Prats M:
Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona 17190, Spain
Alcalde M:
Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona 17190, Spain
Centro Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid 28029, Spain
Sarquella-Brugada G:
Medical Science Department, School of Medicine, University of Girona, Girona 17071, Spain
Arrhythmias Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona 08950, Spain
César-Díaz S:
Arrhythmias Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona 08950, Spain
Arbelo E:
Centro Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid 28029, Spain
Arrhythmias Unit, Hospital Clinic de Barcelona, University of Barcelona, Barcelona 08036, Spain
Fernandez-Falgueras A:
Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona 17190, Spain
Cardiology Service, Hospital Dr. Josep Trueta, University of Girona, Girona 17007, Spain
Coll M:
Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona 17190, Spain
Centro Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid 28029, Spain
Pérez-Serra A:
Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona 17190, Spain
Centro Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid 28029, Spain
Puigmulé M:
Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona 17190, Spain
Centro Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid 28029, Spain
Iglesias A:
Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona 17190, Spain
Centro Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid 28029, Spain
Fiol JV:
Arrhythmias Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona 08950, Spain
Ferrer-Costa C:
Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona 17190, Spain
Olmo BD:
Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona 17190, Spain
Centro Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid 28029, Spain
Picó F:
Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona 17190, Spain
Lopez L:
Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona 17190, Spain
Jordà P:
Centro Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid 28029, Spain
Arrhythmias Unit, Hospital Clinic de Barcelona, University of Barcelona, Barcelona 08036, Spain
García-Álvarez A:
Centro Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid 28029, Spain
Arrhythmias Unit, Hospital Clinic de Barcelona, University of Barcelona, Barcelona 08036, Spain
Llano CT:
Cardiology Service, Hospital Dr. Josep Trueta, University of Girona, Girona 17007, Spain
Toro R:
Medicine Department, School of Medicine, Cadiz 11003, Spain
Grassi S:
Institute of Public Health, Section Legal Medicine, Catholic University, Rome 00153, Italy
Oliva A:
Institute of Public Health, Section Legal Medicine, Catholic University, Rome 00153, Italy
Brugada-Terradellas J:
Centro Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid 28029, Spain
Arrhythmias Unit, Hospital Clinic de Barcelona, University of Barcelona, Barcelona 08036, Spain
Brugada R:
Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona 17190, Spain
Centro Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid 28029, Spain
Medical Science Department, School of Medicine, University of Girona, Girona 17071, Spain
Cardiology Service, Hospital Dr. Josep Trueta, University of Girona, Girona 17007, Spain
Campuzano O:
Cardiovascular Genetics Center, University of Girona-IdIBGi, Girona 17190, Spain
Centro Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid 28029, Spain
Medical Science Department, School of Medicine, University of Girona, Girona 17071, Spain
Green Submitted, gold
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