P296: Evaluating indication for testing based on cluster analysis of human phenotype ontology terms

OMIM-curated disease-causing genes (IMMP2L, NRXN1, and MBD5).The fourth VUS not identified on ES in the first 3 years and both VUS not found in the last 5 years were on the X chromosome (161-741kb in size) and containing all or part of between two and nine genes, at least one of which was disease-causing.Conclusion: First, there has been a change in the analysis of CMA at the testing facility utilized by our center about five years ago (2019-2020), which caused a statistically significant decrease in VUS reported on CMA.This may have a secondary effect of raising the concordance of CNV calls on CMA and ES.Second, discontinuing CMA prior to ES with current protocols at our reference-lab-of-choice has a potential to miss certain CNV (two VUS in 197 specimens from our center in the past 5 years).Based on this limited data review, there appears to be enrichment of X-chromosome CNV escaping detection on ES.Given the high concordance between CMA and ES detection of CNV, we can have confidence to order ES as first-tier test, with consideration of CMA in patients with nondiagnostic ES results, until GS becomes a viable option for more of our patient population.