Clinical impact of rare variants associated with inherited channelopathies: a 5-year update
A proper interpretation of the pathogenicity of rare variants is crucial before clinical translation. Ongoing addition of new data may modify previous variant classifications; however, how often a reanalysis is necessary remains undefined. We aimed to extensively reanalyze rare variants associated w...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| 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:10256/19962 |
| Acceso en línea: | http://hdl.handle.net/10256/19962 |
| Access Level: | acceso abierto |
| Palabra clave: | Cor -- Malalties -- Aspectes genètics Heart -- Diseases -- Genetic aspects Cor -- Malalties -- Patogènesi Heart -- Diseases -- Pathogenesis |
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Clinical impact of rare variants associated with inherited channelopathies: a 5-year updateSarquella Brugada, GeòrgiaFernández-Falgueras, AnnaCesar, SergiArbelo, ElenaColl Vidal, MònicaPerez-Serra, AlexandraPuigmulé, MartaIglesias, AnnaAlcalde Masegu, MireiaVallverdú-Prats, MartaFiol, VictoriaFerrer Costa, CarlesOlmo, Bernat delPicó, FerranLópez López, LauraGarcía Álvarez, AnaJordà, PalomaTirón de Llano, ColomaToro, RocíoGrassi, SimoneOliva, AntonioBrugada Terradellas, JosepBrugada, RamonCampuzano Larrea, OscarCor -- Malalties -- Aspectes genèticsHeart -- Diseases -- Genetic aspectsCor -- Malalties -- PatogènesiHeart -- Diseases -- PathogenesisA proper interpretation of the pathogenicity of rare variants is crucial before clinical translation. Ongoing addition of new data may modify previous variant classifications; however, how often a reanalysis is necessary remains undefined. We aimed to extensively reanalyze rare variants associated with inherited channelopathies originally classified 5 years ago and its clinical impact. In 2016, rare variants identified through genetic analysis were classified following the American College of Medical Genetics and Genomics' recommendations. Five years later, we have reclassified the same variants following the same recommendations but including new available data. Potential clinical implications were discussed. Our cohort included 49 cases of inherited channelopathies diagnosed in 2016. Update show that 18.36% of the variants changed classification mainly due to improved global frequency data. Reclassifications mostly occurred in minority genes associated with channelopathies. Similar percentage of variants remain as deleterious nowadays, located in main known genes (SCN5A, KCNH2 and KCNQ1). In 2016, 69.38% of variants were classified as unknown significance, but now, 53.06% of variants are classified as such, remaining the most common group. No management was modified after translation of genetic data into clinics. After 5 years, nearly 20% of rare variants associated with inherited channelopathies were reclassified. This supports performing periodic reanalyses of no more than 5 years since last classification. Use of newly available data is necessary, especially concerning global frequencies and family segregation. Personalized clinical translation of rare variants can be crucial to management if a significant change in classification is identifiedOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer NatureSpringer2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionpeer-reviewedapplication/pdfhttp://hdl.handle.net/10256/19962Human Genetics, 2021, vol. undef, num. undef, p. undefArticles publicats (D-CM)Sarquella Brugada, Geòrgia Fernández Falgueras, Anna Cesar, Sergi Arbelo, Elena Coll, Monica Perez-Serra, Alexandra Puigmulé, Marta Iglesias, Anna Alcalde Masegu, Mireia Vallverdú-Prats, Marta Fiol, Victoria Ferrer Costa, Carles Olmo, Bernat del Picó, Ferran López, Laura García Álvarez, Ana Jordà, Paloma Tirón de Llano, Coloma Toro, Rocío Grassi, Simone Oliva, Antonio Brugada Terradellas, Josep Brugada, Ramon Campuzano Larrea, Oscar 2021 Clinical impact of rare variants associated with inherited channelopathies: a 5-year update Human Genetics undef undef undefreponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/semantics/altIdentifier/doi/10.1007/s00439-021-02370-4info:eu-repo/semantics/altIdentifier/issn/0340-6717info:eu-repo/semantics/altIdentifier/eissn/1432-1203Reconeixement 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessoai:recercat.cat:10256/199622026-05-29T05:05:01Z |
| dc.title.none.fl_str_mv |
Clinical impact of rare variants associated with inherited channelopathies: a 5-year update |
| title |
Clinical impact of rare variants associated with inherited channelopathies: a 5-year update |
| spellingShingle |
Clinical impact of rare variants associated with inherited channelopathies: a 5-year update Sarquella Brugada, Geòrgia Cor -- Malalties -- Aspectes genètics Heart -- Diseases -- Genetic aspects Cor -- Malalties -- Patogènesi Heart -- Diseases -- Pathogenesis |
| title_short |
Clinical impact of rare variants associated with inherited channelopathies: a 5-year update |
| title_full |
Clinical impact of rare variants associated with inherited channelopathies: a 5-year update |
| title_fullStr |
Clinical impact of rare variants associated with inherited channelopathies: a 5-year update |
| title_full_unstemmed |
Clinical impact of rare variants associated with inherited channelopathies: a 5-year update |
| title_sort |
Clinical impact of rare variants associated with inherited channelopathies: a 5-year update |
| dc.creator.none.fl_str_mv |
Sarquella Brugada, Geòrgia Fernández-Falgueras, Anna Cesar, Sergi Arbelo, Elena Coll Vidal, Mònica Perez-Serra, Alexandra Puigmulé, Marta Iglesias, Anna Alcalde Masegu, Mireia Vallverdú-Prats, Marta Fiol, Victoria Ferrer Costa, Carles Olmo, Bernat del Picó, Ferran López López, Laura García Álvarez, Ana Jordà, Paloma Tirón de Llano, Coloma Toro, Rocío Grassi, Simone Oliva, Antonio Brugada Terradellas, Josep Brugada, Ramon Campuzano Larrea, Oscar |
| author |
Sarquella Brugada, Geòrgia |
| author_facet |
Sarquella Brugada, Geòrgia Fernández-Falgueras, Anna Cesar, Sergi Arbelo, Elena Coll Vidal, Mònica Perez-Serra, Alexandra Puigmulé, Marta Iglesias, Anna Alcalde Masegu, Mireia Vallverdú-Prats, Marta Fiol, Victoria Ferrer Costa, Carles Olmo, Bernat del Picó, Ferran López López, Laura García Álvarez, Ana Jordà, Paloma Tirón de Llano, Coloma Toro, Rocío Grassi, Simone Oliva, Antonio Brugada Terradellas, Josep Brugada, Ramon Campuzano Larrea, Oscar |
| author_role |
author |
| author2 |
Fernández-Falgueras, Anna Cesar, Sergi Arbelo, Elena Coll Vidal, Mònica Perez-Serra, Alexandra Puigmulé, Marta Iglesias, Anna Alcalde Masegu, Mireia Vallverdú-Prats, Marta Fiol, Victoria Ferrer Costa, Carles Olmo, Bernat del Picó, Ferran López López, Laura García Álvarez, Ana Jordà, Paloma Tirón de Llano, Coloma Toro, Rocío Grassi, Simone Oliva, Antonio Brugada Terradellas, Josep Brugada, Ramon Campuzano Larrea, Oscar |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Cor -- Malalties -- Aspectes genètics Heart -- Diseases -- Genetic aspects Cor -- Malalties -- Patogènesi Heart -- Diseases -- Pathogenesis |
| topic |
Cor -- Malalties -- Aspectes genètics Heart -- Diseases -- Genetic aspects Cor -- Malalties -- Patogènesi Heart -- Diseases -- Pathogenesis |
| description |
A proper interpretation of the pathogenicity of rare variants is crucial before clinical translation. Ongoing addition of new data may modify previous variant classifications; however, how often a reanalysis is necessary remains undefined. We aimed to extensively reanalyze rare variants associated with inherited channelopathies originally classified 5 years ago and its clinical impact. In 2016, rare variants identified through genetic analysis were classified following the American College of Medical Genetics and Genomics' recommendations. Five years later, we have reclassified the same variants following the same recommendations but including new available data. Potential clinical implications were discussed. Our cohort included 49 cases of inherited channelopathies diagnosed in 2016. Update show that 18.36% of the variants changed classification mainly due to improved global frequency data. Reclassifications mostly occurred in minority genes associated with channelopathies. Similar percentage of variants remain as deleterious nowadays, located in main known genes (SCN5A, KCNH2 and KCNQ1). In 2016, 69.38% of variants were classified as unknown significance, but now, 53.06% of variants are classified as such, remaining the most common group. No management was modified after translation of genetic data into clinics. After 5 years, nearly 20% of rare variants associated with inherited channelopathies were reclassified. This supports performing periodic reanalyses of no more than 5 years since last classification. Use of newly available data is necessary, especially concerning global frequencies and family segregation. Personalized clinical translation of rare variants can be crucial to management if a significant change in classification is identified |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion peer-reviewed |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10256/19962 |
| url |
http://hdl.handle.net/10256/19962 |
| dc.language.none.fl_str_mv |
Inglés |
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Inglés |
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info:eu-repo/semantics/altIdentifier/doi/10.1007/s00439-021-02370-4 info:eu-repo/semantics/altIdentifier/issn/0340-6717 info:eu-repo/semantics/altIdentifier/eissn/1432-1203 |
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Reconeixement 4.0 Internacional http://creativecommons.org/licenses/by/4.0 info:eu-repo/semantics/openAccess |
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Reconeixement 4.0 Internacional http://creativecommons.org/licenses/by/4.0 |
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openAccess |
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application/pdf |
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Springer |
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Springer |
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Human Genetics, 2021, vol. undef, num. undef, p. undef Articles publicats (D-CM) Sarquella Brugada, Geòrgia Fernández Falgueras, Anna Cesar, Sergi Arbelo, Elena Coll, Monica Perez-Serra, Alexandra Puigmulé, Marta Iglesias, Anna Alcalde Masegu, Mireia Vallverdú-Prats, Marta Fiol, Victoria Ferrer Costa, Carles Olmo, Bernat del Picó, Ferran López, Laura García Álvarez, Ana Jordà, Paloma Tirón de Llano, Coloma Toro, Rocío Grassi, Simone Oliva, Antonio Brugada Terradellas, Josep Brugada, Ramon Campuzano Larrea, Oscar 2021 Clinical impact of rare variants associated with inherited channelopathies: a 5-year update Human Genetics undef undef undef reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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