Advancing Precision in Genomics: Quest Diagnostics’ Contributions to ACMG 2025

Peter Bui, Colyn Cain, Julie Cox, Mark Fleharty, Yueyao Gao, Benjamin Hilton, Sean Hofherr, Katie Larkin, Guang Li, David Marsh, Sarah South, and Reha Toydemir will present their poster (P629), “Analytical Performance Evaluation of Whole Genome Sequencing as First-Line Genetic Testing for Intellectual Development Disorders and Congenital Malformations.” Their research evaluates whole genome sequencing (WGS) as an alternative to chromosomal microarray analysis (CMA). Results show WGS is technically equivalent to CMA while also detecting fragile X syndrome, supporting its use as a comprehensive first-line genetic test. 

“Empowering Clinicians to Resolve VUS: Presenting VUS Clarification Outcomes” (P669) by Laura Fuqua, Eija Seppälä, Mia Toivonen , Michelle Paczosa, Shaochun Bai, Jennifer Keller-Ramey, Kimberly Gall, Julie Hathaway, Allison Sluyters, Juha Koskenvuo will demonstrate the VUS Clarification Service program’s success in reclassification of VUS and its significant benefits to participants and health care providers.

Zöe Powis, Khalida Liaquat, Raveen Basran, and Zhenyuan Wang will present their poster (P271), “Two Copies, One Condition? Understanding APOE Allele State in over 14,000 Symptomatic Patients.” This study examines the largest cohort of symptomatic individuals undergoing APOE testing, comparing symptoms in those with homozygous APOE4 alleles. These findings provide critical insights into neurodegenerative disease risk and potential early intervention strategies. 

John D. Murdoch and Glenn A. Maston will present their poster (P196), “Significance of Near-Canonical Conserved Splice Region Nucleotides”. Their research analyzes the effects of variants at the +5 and -3 positions just outside of the canonical splice sites, augmented by internal Quest variant interpretation data, and discusses whether partial weighting of the Pathogenic Very Strong 1 (PVS1) criterion might be applied in these situations. 

“A Novel MRTFB Missense Variant, c.479T>C p.(Leu160Pro), in a School-Aged Girl With Neurodevelopmental Disorder” (P480) from Rebecca Nakles-Taylor, Michelle Paczosa, Shaochun Bai, Helena Kääriäinen, Maria Calvo del Castillo, Gail Kline, Linda Marie Randolph will describe a case report expands the clinical understanding of MKL2-related neurodevelopmental disorders as few previous cases have been previously published.