Secondary Findings Using Broad Pan Cardiomyopathy and Arrhythmia Panels in Patients With a Personal or Family History of Inherited Cardiomyopathy or Arrhythmia Syndrome

Abstract

With broad panels and whole exome or genome sequencing, there is the potential for secondary findings, which include pathogenic/likely pathogenic variants or variants of uncertain significance in genes that are unrelated to the primary clinical indication for the testing. No study examined the frequency and implications of secondary findings when using a broad panel for inherited cardiomyopathy or arrhythmia syndromes. We performed a retrospective review of the primary indications for genetic testing, tests performed, and genetic test results to identify secondary findings in patients seen in the Inherited Cardiovascular Disease Clinic for a personal or family history of (possible) inherited cardiomyopathy, inherited arrhythmia syndrome, previous cardiac arrest, or family history of sudden cardiac death. Of 325 probands and 20 family members who had genetic testing, with no-cost broad cardiomyopathy and arrhythmia panel, 4 probands (1.2%) and 4 family members (5%) had pathogenic/likely pathogenic variants in autosomal dominant genes, unrelated to the primary reason for testing. In conclusion, the prevalence of secondary findings using broad cardiomyopathy and arrhythmia panel in patients with personal or family history of inherited cardiomyopathy or arrhythmia was ∼2.2%. Our findings suggest that with appropriate genetic counseling, broad panels might be considered over disease-specific panels because of the relatively high prevalence of secondary findings that positively affect patient care and would not have been identified with more targeted testing.