The diffusion of next-generation sequencing (NGS)-based approaches allows for the identification of pathogenic mutations of cardiomyopathies and channelopathies in more than 200 different genes. Since genes considered uncommon for a clinical phenotype are also now included in molecular testing, the detection rate of disease-causing variants has increased. Here, we report the prevalence of genetic variants detected by using a NGS custom panel in a cohort of 133 patients with inherited cardiomyopathies (n = 77) or channelopathies (n = 56). We identified 82 variants, of which 50 (61%) were identified in genes without a strong or definitive evidence of disease association according to the NIH-funded Clinical Genome Resource (ClinGen; "uncommon genes"). Among these, 35 (70%) were variants of unknown significance (VUSs), 13 (26%) were pathogenic (P) or likely pathogenic (LP) mutations, and 2 (4%) benign (B) or likely benign (LB) variants according to American College of Medical Genetics (ACMG) classifications. These data reinforce the need for the screening of uncommon genes in order to increase the diagnostic sensitivity of the genetic testing of inherited cardiomyopathies and channelopathies by allowing for the identification of mutations in genes that are not usually explored due to a currently poor association with the clinical phenotype.

Next-Generation Sequencing Gene Panels in Inheritable Cardiomyopathies and Channelopathies: Prevalence of Pathogenic Variants and Variants of Unknown Significance in Uncommon Genes / Mazzaccara, Cristina; Lombardi, Raffaella; Mirra, Bruno; Barretta, Ferdinando; Esposito, Maria Valeria; Uomo, Fabiana; Caiazza, Martina; Monda, Emanuele; Losi, Maria Angela; Limongelli, Giuseppe; D'Argenio, Valeria; Frisso, Giulia. - In: BIOMOLECULES. - ISSN 2218-273X. - 12:10(2022), p. 1417. [10.3390/biom12101417]

Next-Generation Sequencing Gene Panels in Inheritable Cardiomyopathies and Channelopathies: Prevalence of Pathogenic Variants and Variants of Unknown Significance in Uncommon Genes

Mazzaccara, Cristina;Lombardi, Raffaella;Esposito, Maria Valeria;Losi, Maria Angela;Frisso, Giulia
Ultimo
2022

Abstract

The diffusion of next-generation sequencing (NGS)-based approaches allows for the identification of pathogenic mutations of cardiomyopathies and channelopathies in more than 200 different genes. Since genes considered uncommon for a clinical phenotype are also now included in molecular testing, the detection rate of disease-causing variants has increased. Here, we report the prevalence of genetic variants detected by using a NGS custom panel in a cohort of 133 patients with inherited cardiomyopathies (n = 77) or channelopathies (n = 56). We identified 82 variants, of which 50 (61%) were identified in genes without a strong or definitive evidence of disease association according to the NIH-funded Clinical Genome Resource (ClinGen; "uncommon genes"). Among these, 35 (70%) were variants of unknown significance (VUSs), 13 (26%) were pathogenic (P) or likely pathogenic (LP) mutations, and 2 (4%) benign (B) or likely benign (LB) variants according to American College of Medical Genetics (ACMG) classifications. These data reinforce the need for the screening of uncommon genes in order to increase the diagnostic sensitivity of the genetic testing of inherited cardiomyopathies and channelopathies by allowing for the identification of mutations in genes that are not usually explored due to a currently poor association with the clinical phenotype.
2022
Next-Generation Sequencing Gene Panels in Inheritable Cardiomyopathies and Channelopathies: Prevalence of Pathogenic Variants and Variants of Unknown Significance in Uncommon Genes / Mazzaccara, Cristina; Lombardi, Raffaella; Mirra, Bruno; Barretta, Ferdinando; Esposito, Maria Valeria; Uomo, Fabiana; Caiazza, Martina; Monda, Emanuele; Losi, Maria Angela; Limongelli, Giuseppe; D'Argenio, Valeria; Frisso, Giulia. - In: BIOMOLECULES. - ISSN 2218-273X. - 12:10(2022), p. 1417. [10.3390/biom12101417]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/901820
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