P363: Analyzing the genetic causes of pediatric inherited cardiomyopathy in Middle Eastern patients

25% of cases (n=4) were determined to be diagnostic and 31.25% of cases (n=5) were determined to be uncertain.Five of the returned variants were SNVs or indels, three were triplet repeat expansions, one was an insertion, and one was a copy number variant (CNV).Genes containing reportable variants included ATXN8OS, C2CD3, CADM3, COL3A1, DNMT3A, HTT, SYNE2, and TSC2. Conclusion:This early data demonstrates a potential utility for lrGS as a diagnostic tool in the setting of this state-funded research study, particularly in the identification of a wide variety of variant types using a single assay, including variants that would not have been identified via srGS, such as triplet repeat expansions in ATXN8OS and HTT.Additional benefits of this approach are the availability of this emerging technology to eligible participants at no cost and the structure of the AGHI, which benefits from working groups with a variety of professional perspectives.The AGHI bioethics working group is particularly valuable in this regard, as they advise on the return of results that would not have previously been identified via srGS but have ethical implications for returning to participants (triplet repeat expansions in HTT, for example).Limitations to our study include the lack of a direct comparison between lrGS and srGS and the inability to clinically-confirm variants that are not detectable via Sanger sequencing (though downstream commercial clinical testing may be available to participants).Desired future directions for this cohort include increasing enrollment and diagnostic yield, comparison to other ongoing lrGS efforts, and demonstration of a reduced time-to-diagnosis by avoiding a multiple assay, stepwise approach.