Background. Pathogenic and likely pathogenic variants associated with arrhythmogenic right ventricular cardiomyopathy (ARVC), dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) are recommended to be reported as secondary findings in genome sequencing studies. This provides opportunities for early diagnosis, but also fuels uncertainty in variant carriers (G+), since disease penetrance is incomplete. We assessed the prevalence and disease expression of G+ in the general population. Methods. We identified pathogenic and likely pathogenic variants associated with ARVC, DCM and/or HCM in 200,643 UK Biobank individuals, who underwent whole exome sequencing. We calculated the prevalence of G+ and analysed the frequency of cardiomyopathy/heart failure diagnosis. In undiagnosed individuals, we analysed early signs of disease expression using available electrocardiography and cardiac magnetic resonance imaging data. Results. We found a prevalence of 1:578, 1:251 and 1:149 for pathogenic and likely pathogenic variants associated with ARVC, DCM and HCM respectively. Compared to controls, cardiovascular mortality was higher in DCM G+ (OR 1.67 [95% CI 1.04;2.59], p=0.030), but similar in ARVC and HCM G+ (p≥0.100). Cardiomyopathy or heart failure diagnosis were more frequent in DCM G+ (OR 3.66 [95% CI 2.24;5.81], p=4.9×10-7) and HCM G+ (OR 3.03 [95% CI 1.98;4.56], p=5.8×10-7), but comparable in ARVC G+ (p=0.172). In contrast, ARVC G+ had more ventricular arrhythmias (p=3.3×10-4). In undiagnosed individuals, left ventricular ejection fraction was reduced in DCM G+ (p=0.009). Conclusions. In the general population, pathogenic and likely pathogenic variants associated with ARVC, DCM or HCM are not uncommon. Although G+ have increased mortality and morbidity, disease penetrancein these carriers from the general population remains low (1.2-3.1%). Follow-up decisions in case of incidental findings should not be based solely on a variant, but on multiple factors, including family history and disease expression.

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