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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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Autores principales: Vallverdú-Prats, Marta, Alcalde, Mireia, Sarquella-Brugada, Georgia, Cesar, Sergi, Arbelo, Elena, Fernandez-Falgueras, Anna, Coll, Mónica, Pérez-Serra, Alexandra, Puigmulé, Marta, Iglesias, Anna, Fiol, Victoria, Ferrer-Costa, Carles, del Olmo, Bernat, Picó, Ferran, Lopez, Laura, Jordà, Paloma, García-Álvarez, Ana, Tirón de Llano, Coloma, Toro, Rocío, Grassi, Simone, Oliva, Antonio, Brugada, Josep, Brugada, Ramon, Campuzano, Oscar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996798/
https://www.ncbi.nlm.nih.gov/pubmed/33652588
http://dx.doi.org/10.3390/jpm11030162
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author Vallverdú-Prats, Marta
Alcalde, Mireia
Sarquella-Brugada, Georgia
Cesar, Sergi
Arbelo, Elena
Fernandez-Falgueras, Anna
Coll, Mónica
Pérez-Serra, Alexandra
Puigmulé, Marta
Iglesias, Anna
Fiol, Victoria
Ferrer-Costa, Carles
del Olmo, Bernat
Picó, Ferran
Lopez, Laura
Jordà, Paloma
García-Álvarez, Ana
Tirón de Llano, Coloma
Toro, Rocío
Grassi, Simone
Oliva, Antonio
Brugada, Josep
Brugada, Ramon
Campuzano, Oscar
author_facet Vallverdú-Prats, Marta
Alcalde, Mireia
Sarquella-Brugada, Georgia
Cesar, Sergi
Arbelo, Elena
Fernandez-Falgueras, Anna
Coll, Mónica
Pérez-Serra, Alexandra
Puigmulé, Marta
Iglesias, Anna
Fiol, Victoria
Ferrer-Costa, Carles
del Olmo, Bernat
Picó, Ferran
Lopez, Laura
Jordà, Paloma
García-Álvarez, Ana
Tirón de Llano, Coloma
Toro, Rocío
Grassi, Simone
Oliva, Antonio
Brugada, Josep
Brugada, Ramon
Campuzano, Oscar
author_sort Vallverdú-Prats, Marta
collection PubMed
description 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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spelling pubmed-79967982021-03-27 Rare Variants Associated with Arrhythmogenic Cardiomyopathy: Reclassification Five Years Later Vallverdú-Prats, Marta Alcalde, Mireia Sarquella-Brugada, Georgia Cesar, Sergi Arbelo, Elena Fernandez-Falgueras, Anna Coll, Mónica Pérez-Serra, Alexandra Puigmulé, Marta Iglesias, Anna Fiol, Victoria Ferrer-Costa, Carles del Olmo, Bernat Picó, Ferran Lopez, Laura Jordà, Paloma García-Álvarez, Ana Tirón de Llano, Coloma Toro, Rocío Grassi, Simone Oliva, Antonio Brugada, Josep Brugada, Ramon Campuzano, Oscar J Pers Med Article 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. MDPI 2021-02-26 /pmc/articles/PMC7996798/ /pubmed/33652588 http://dx.doi.org/10.3390/jpm11030162 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Vallverdú-Prats, Marta
Alcalde, Mireia
Sarquella-Brugada, Georgia
Cesar, Sergi
Arbelo, Elena
Fernandez-Falgueras, Anna
Coll, Mónica
Pérez-Serra, Alexandra
Puigmulé, Marta
Iglesias, Anna
Fiol, Victoria
Ferrer-Costa, Carles
del Olmo, Bernat
Picó, Ferran
Lopez, Laura
Jordà, Paloma
García-Álvarez, Ana
Tirón de Llano, Coloma
Toro, Rocío
Grassi, Simone
Oliva, Antonio
Brugada, Josep
Brugada, Ramon
Campuzano, Oscar
Rare Variants Associated with Arrhythmogenic Cardiomyopathy: Reclassification Five Years Later
title Rare Variants Associated with Arrhythmogenic Cardiomyopathy: Reclassification Five Years Later
title_full Rare Variants Associated with Arrhythmogenic Cardiomyopathy: Reclassification Five Years Later
title_fullStr Rare Variants Associated with Arrhythmogenic Cardiomyopathy: Reclassification Five Years Later
title_full_unstemmed Rare Variants Associated with Arrhythmogenic Cardiomyopathy: Reclassification Five Years Later
title_short Rare Variants Associated with Arrhythmogenic Cardiomyopathy: Reclassification Five Years Later
title_sort rare variants associated with arrhythmogenic cardiomyopathy: reclassification five years later
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996798/
https://www.ncbi.nlm.nih.gov/pubmed/33652588
http://dx.doi.org/10.3390/jpm11030162
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