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 (class3), likely (class4), and certain (class5) 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% class5; 4.2% class4), and one or multiple class3 variants in 34.8%. In 1970 patients tested on the cardiomyopathy panel, likely pathogenic and pathogenic variants were detected in 19.8% (12.0% class5; 7.9% class4), and one or multiple class3 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 alarge increase of class3 variants.ConclusionOverall detection rates (class3, 4, and 5 variants) in adiagnostic setting are 44% and 61% for the arrhythmia and cardiomyopathy gene panel respectively, with only asmall 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.