ArticleNetherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation2019
Large next-generation sequencing gene panels in genetic heart disease: yield of pathogenic variants and variants of unknown significance.
Article in Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 65 citations in OpenAlex.
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- Appropriate time interval to update ambiguous genetic diagnosis in inherited arrhythmogenic syndromes.iScience · 2025Article
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- Troponin I - a comprehensive review of its function, structure, evolution, and role in muscle diseases.Animal cells and systems · 2025Review
- Novel causativeFrontiers in genetics · 2025Article
- Implementation of genetic testing for heritable cardiac conditions: A scoping review.Genetics in medicine open · 2025Review
- Actionable Variants of Unknown Significance in Inherited Arrhythmogenic Syndromes: A Further Step Forward in Genetic Diagnosis.Biomedicines · 2024Article
- Utilization of automated cilia analysis to characterize novel INPP5E variants in patients with non-syndromic retinitis pigmentosa.European journal of human genetics : EJHG · 2024Article
- Performance of a Protein Language Model for Variant Annotation in Cardiac Disease.Journal of the American Heart Association · 2024Article
- A Rare Coincidence of Three Inherited Diseases in a Family with Cardiomyopathy and Multiple Extracardiac Abnormalities.International journal of molecular sciences · 2024Article
- Exploring TTN variants as genetic insights into cardiomyopathy pathogenesis and potential emerging clues to molecular mechanisms in cardiomyopathies.Scientific reports · 2024Review
- Mechanisms of RBM20 Cardiomyopathy: Insights From Model Systems.Circulation. Genomic and precision medicine · 2024Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGenetic heterogeneity is common in inherited cardiac diseases. Next-generation sequencing gene panels are therefore suitable for genetic diagnosis. We describe the results of implementation of cardiomyopathy and arrhythmia gene panels in clinical care.
methodsWe present detection rates for variants with unknown (class 3), likely (class 4), and certain (class 5) pathogenicity in cardiogenetic gene panels since their introduction into diagnostics.
resultsIn 936 patients tested on the arrhythmia panel, likely pathogenic and pathogenic variants were detected in 8.8% (4.6% class 5; 4.2% class 4), and one or multiple class 3 variants in 34.8%. In 1970 patients tested on the cardiomyopathy panel, likely pathogenic and pathogenic variants were detected in 19.8% (12.0% class 5; 7.9% class 4), and one or multiple class 3 variants in 40.8%. Detection rates of all different classes of variants increased with the increasing number of genes on the cardiomyopathy gene panel. Multiple variants were detected in 11.7% and 28.5% of patients on the arrhythmia and cardiomyopathy panels respectively. In more recent larger versions of the cardiomyopathy gene panel the detection rate of likely pathogenic and pathogenic variants only slightly increased, but was associated with a large increase of class 3 variants.
conclusionOverall detection rates (class 3, 4, and 5 variants) in a diagnostic setting are 44% and 61% for the arrhythmia and cardiomyopathy gene panel respectively, with only a small minority of likely pathogenic and pathogenic variants (8.8% and 19.8% respectively). Larger gene panels can increase the detection rate of likely pathogenic and pathogenic variants, but mainly increase the frequency of variants of unknown pathogenicity.
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