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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-7996798 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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