Current standard of care clinical genetic testing relies on multiple testing modalities to detect known genomic variation, including karyotype, microarray, FISH, short read sequencing, MLPA, fragment analysis, methylation assays, and others. For some laboratories, this may require the utilization of multiple reference laboratories, but HiFi long-read genome sequencing (lrGS) is a single test that can simultaneously evaluate methylation, copy number variation, structural variation, expansion disorders, X-activation studies, telomere length, and single nucleotide variation with haplotype phasing, as well as variants in pseudogenes and other regions previously inaccessible by short read genome sequencing (srGS). HiFi lrGS was launched as a first line comprehensive test at Children’s Mercy Hopsital in October 2023. This presentation will compare a clinical HiFi lrGS workflow to a control cohort that received standard of care testing, evaluating potential diagnostic rates, number of tests ordered, and time it could take to diagnosis.