40 - Unlocking answers faster with whole exome sequencing (17 min)

Whole exome sequencing (WES) is transforming the way genetic testing has moved from a research tool to an increasingly important first-line diagnostic test for many patients. In this episode, Rebecca Johnson Wheeler, MS, CGC and Steve Keiles, MS, CGC discuss how advances in WES, growing insurance coverage, and expanding clinical applications are helping patients get answers faster while improving targeted treatment and care. This episode will Review current trends and guidelines driving increased adoption of whole exome sequencing in clinical practice (3:20) Discuss the potential benefits and limitations of whole exome sequencing including the important components of the test (4:55) Explain how the clinical interpretation of WES may change over time upon reevaluation as new patient information becomes available (8:15) Evaluate how genetic expertise can support clinicians throughout the testing and interpretation process (13:30) Date: June 2026 Speaker(s): Rebecca Johnson Wheeler, MS, CGC; Steve Keiles, MS, CGC Contributor(s): Rebecca Johnson Wheeler, MS, CGC; Steve Keiles, MS, CGC; Maeson Latsko, PhD; Meenakshi Mahey Kumar, MS, CGC; Whitney Dodge, MS, CGC; Emily Partack, MS, CGC   Additional resources: Test information: https://www.questdiagnostics.com/healthcare-professionals/about-our-tests/genetics/exome Blog: https://www.questdiagnostics.com/our-company/actions-insights/2026-blogs/considering-mitochondrial-genomes-in-whole-exome-testing Ordering information: Whole Exome | Test Detail | Quest Diagnostics Whole Exome Family Trio | Test Detail | Quest Diagnostics Whole Exome Family Duo | Test Detail | Quest Diagnostics References: Reinholdt L, Chesler E, Pera M, Rosenthal N. The rare-to-common disease journey: a winding road to new therapies. Trends Genet. 2025;41(9):762-773. doi:10.1016/j.tig.2025.05.003 Manickam K, McClain MR, Demmer LA, et al. Exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability: an evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2021;23(11):2029-2037. doi:10.1038/s41436-021-01242-6 Smith L, Malinowski J, Ceulemans S, et al. Genetic testing and counseling for the unexplained epilepsies: an evidence-based practice guideline of the National Society of Genetic Counselors. J Genet Couns. 2023;32(2):266-280. doi:10.1002/jgc4.1646 Rodan LH, Stoler J, Chen E, Geleske T; Council on Genetics. Genetic evaluation of the child with intellectual disability or global developmental delay: clinical report. Pediatrics. 2025;156(1):e2025072219. doi:10.1542/peds.2025-072219 LJ, Minoche AE, Schofield D, et al. Whole exome and genome sequencing in mendelian disorders: a diagnostic and health economic analysis. Eur J Hum Genet. 2022;30(10):1121-1131. doi:10.1038/s41431-022-01162-2 van de Kamp JM, Betsalel OT, Mercimek-Mahmutoglu S, et al. Phenotype and genotype in 101 males with X-linked creatine transporter deficiency. J Med Genet. 2013;50(7):463-472. doi:10.1136/jmedgenet-2013-101658 Dunbar M, Jaggumantri S, Sargent M, Stockler-Ipsiroglu S, van Karnebeek CD. Treatment of X-linked creatine transporter (SLC6A8) deficiency: systematic review of the literature and three new cases. Mol Genet Metab. 2014;112(4):259-274. doi:10.1016/j.ymgme.2014.05.011