Ce-482906-003 Results From Genetic Evaluation of Patients Referred to an Atrial Fibrillation Precision Medicine Clinic

conditions associated with sudden death (e.g., sudden unexplained death in epilepsy) to identify P/LP variants and correlated genotypes with postmortem phenotypes and 2) evaluated family history of decedents with high-risk phenotypes: premature CAD, aortic aneurysm and dissection, and cardiomyopathy [CM], arrhythmogenic right ventricular CM, hypertrophic CM, bicuspid aortic valve, and primary electrical.Results: Between 02/2011 and 01/2018, 856 pSCD (66% CV causes, 34% non-CV) were autopsied; 306 (36%) consented to genetic testing (mean age 62 years, 74% male).Families of 75 pSCDs (9%) with high-risk phenotypes were referred to genetic counselor; 18 consented.14 dominant or X-linked P/LP variants were found in 13 pSCDs (yield 4%).The majority of P/LP (8/14) cases were non-concordant with postmortem phenotype and only 5 had a P/LP variant concordant with cause of death (corrected yield 1.6%).The corrected yield was largely unchanged when restricting to autopsy confirmed CV causes (2%) or high-risk phenotypes (2.7%).Family screening of highrisk cases identified 50% (9/18) with a history of a related condition or sudden death despite negative testing in the proband.Conclusion: In this 7-year countywide study of unselected adult sudden deaths, the corrected yield of genetic testing concordant with autopsy phenotype was low (1.6%).The total burden of potentially heritable sudden death was enhanced by familial screening of cases with high risk phenotypes (50% by family history vs. 2.7% by genetic testing).These results evidence a phenotype-first approach is needed to guide genetic testing and familial screening in sudden deaths.