What is Whole Exome Sequencing and when is it medically useful?

Whole Exome Sequencing (WES) is an advanced genetic test that analyzes all protein-coding regions (exons) of your genes, representing about 1-2% of your entire genome but containing approximately 85% of disease-causing mutations. This comprehensive analysis sequences roughly 20,000 genes simultaneously, identifying genetic variants that may explain mysterious medical conditions or guide treatment decisions.

WES proves invaluable when patients present with complex, undiagnosed conditions after traditional testing fails. It's particularly useful for children with developmental delays, intellectual disabilities, or multiple congenital anomalies where the underlying cause remains unknown. Adults with rare diseases, unexplained neurological conditions, or family histories suggesting genetic disorders also benefit from WES. The test can identify single-gene disorders, provide molecular diagnoses that end diagnostic odysseys, and occasionally reveal actionable findings leading to specific treatments.

The process involves extracting DNA from blood or saliva, capturing and sequencing exonic regions, then analyzing variants against databases of known disease-causing mutations. Genetic counselors and medical geneticists interpret results, distinguishing pathogenic variants from benign differences. Diagnostic yield ranges from 25-50% depending on the clinical indication.

WES offers advantages over testing individual genes sequentially—it's comprehensive, often more cost-effective, and may uncover unexpected diagnoses. However, it generates massive data requiring expert interpretation, may reveal variants of uncertain significance causing anxiety, and occasionally discovers incidental findings unrelated to the original concern.

Insurance coverage varies but generally requires medical necessity documentation. Results typically take 6-12 weeks and should always include pre-test and post-test genetic counseling to ensure patients understand implications for themselves and family members, including potential inherited conditions children might carry.