What are the limitations of whole exome sequencing?

The biggest limitation of whole exome sequencing (WES) is that it does not target 100% of the genes in the genome. Instead it focuses only on exons or coding proteins, which make up 1 – 2% of the entire genome. As a result, disease-causing variants in the missed exons go undetected. WES is capable of detecting only a limited number of mutations such as mitochondrial genome mutations, large rearrangements, epigenetic factors, and large deletions or duplications. It is unable to detect structural variations, including inversions, translocations and copy number variants. Because of these limitations, researchers often have to perform additional testing in order to study missed regions, look for elusive variants, and confirm the presence of detected variants.