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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Journal of Personalized Medicine |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-4426/11/3/162 |
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doaj-6e3d3402ba934ad89e212207e1975177 |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Marta Vallverdú-Prats Mireia Alcalde Georgia Sarquella-Brugada Sergi Cesar Elena Arbelo Anna Fernandez-Falgueras Mónica Coll Alexandra Pérez-Serra Marta Puigmulé Anna Iglesias Victoria Fiol Carles Ferrer-Costa Bernat del Olmo Ferran Picó Laura Lopez Paloma Jordà Ana García-Álvarez Coloma Tirón de Llano Rocío Toro Simone Grassi Antonio Oliva Josep Brugada Ramon Brugada Oscar Campuzano |
| spellingShingle |
Marta Vallverdú-Prats Mireia Alcalde Georgia Sarquella-Brugada Sergi Cesar Elena Arbelo Anna Fernandez-Falgueras Mónica Coll Alexandra Pérez-Serra Marta Puigmulé Anna Iglesias Victoria Fiol Carles Ferrer-Costa Bernat del Olmo Ferran Picó Laura Lopez Paloma Jordà Ana García-Álvarez Coloma Tirón de Llano Rocío Toro Simone Grassi Antonio Oliva Josep Brugada Ramon Brugada Oscar Campuzano Rare Variants Associated with Arrhythmogenic Cardiomyopathy: Reclassification Five Years Later Journal of Personalized Medicine sudden cardiac death arrhythmogenic cardiomyopathy genetics rare variants reclassification |
| author_facet |
Marta Vallverdú-Prats Mireia Alcalde Georgia Sarquella-Brugada Sergi Cesar Elena Arbelo Anna Fernandez-Falgueras Mónica Coll Alexandra Pérez-Serra Marta Puigmulé Anna Iglesias Victoria Fiol Carles Ferrer-Costa Bernat del Olmo Ferran Picó Laura Lopez Paloma Jordà Ana García-Álvarez Coloma Tirón de Llano Rocío Toro Simone Grassi Antonio Oliva Josep Brugada Ramon Brugada Oscar Campuzano |
| author_sort |
Marta Vallverdú-Prats |
| title |
Rare Variants Associated with Arrhythmogenic Cardiomyopathy: Reclassification Five Years Later |
| title_short |
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_sort |
rare variants associated with arrhythmogenic cardiomyopathy: reclassification five years later |
| publisher |
MDPI AG |
| series |
Journal of Personalized Medicine |
| issn |
2075-4426 |
| publishDate |
2021-02-01 |
| 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. |
| topic |
sudden cardiac death arrhythmogenic cardiomyopathy genetics rare variants reclassification |
| url |
https://www.mdpi.com/2075-4426/11/3/162 |
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doaj-6e3d3402ba934ad89e212207e19751772021-02-27T00:00:37ZengMDPI AGJournal of Personalized Medicine2075-44262021-02-011116216210.3390/jpm11030162Rare Variants Associated with Arrhythmogenic Cardiomyopathy: Reclassification Five Years LaterMarta Vallverdú-Prats0Mireia Alcalde1Georgia Sarquella-Brugada2Sergi Cesar3Elena Arbelo4Anna Fernandez-Falgueras5Mónica Coll6Alexandra Pérez-Serra7Marta Puigmulé8Anna Iglesias9Victoria Fiol10Carles Ferrer-Costa11Bernat del Olmo12Ferran Picó13Laura Lopez14Paloma Jordà15Ana García-Álvarez16Coloma Tirón de Llano17Rocío Toro18Simone Grassi19Antonio Oliva20Josep Brugada21Ramon Brugada22Oscar Campuzano23Cardiovascular Genetics Center, University of Girona—IdIBGi, Girona 17190, SpainCardiovascular Genetics Center, University of Girona—IdIBGi, Girona 17190, SpainMedical Science Department, School of Medicine, University of Girona, Girona 17071, SpainArrhythmias Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona 08950, SpainCentro Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid 28029, SpainCardiovascular Genetics Center, University of Girona—IdIBGi, Girona 17190, SpainCardiovascular Genetics Center, University of Girona—IdIBGi, Girona 17190, SpainCardiovascular Genetics Center, University of Girona—IdIBGi, Girona 17190, SpainCardiovascular Genetics Center, University of Girona—IdIBGi, Girona 17190, SpainCardiovascular Genetics Center, University of Girona—IdIBGi, Girona 17190, SpainArrhythmias Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona 08950, SpainCardiovascular Genetics Center, University of Girona—IdIBGi, Girona 17190, SpainCardiovascular Genetics Center, University of Girona—IdIBGi, Girona 17190, SpainCardiovascular Genetics Center, University of Girona—IdIBGi, Girona 17190, SpainCardiovascular Genetics Center, University of Girona—IdIBGi, Girona 17190, SpainCentro Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid 28029, SpainCentro Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid 28029, SpainCardiology Service, Hospital Dr. Josep Trueta, University of Girona, Girona 17007, SpainMedicine Department, School of Medicine, Cadiz 11003, SpainInstitute of Public Health, Section Legal Medicine, Catholic University, Rome 00153, ItalyInstitute of Public Health, Section Legal Medicine, Catholic University, Rome 00153, ItalyCentro Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid 28029, SpainCardiovascular Genetics Center, University of Girona—IdIBGi, Girona 17190, SpainCardiovascular Genetics Center, University of Girona—IdIBGi, Girona 17190, SpainGenetic 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.https://www.mdpi.com/2075-4426/11/3/162sudden cardiac deatharrhythmogenic cardiomyopathygeneticsrare variantsreclassification |