Limitations of the exome sequencing

Exome sequencing does not target 100% of the genes in the human genome; approximately 97% of exons are targeted. However, ~10% of exons may not be covered at sufficient levels to reliably call heterozygous variants. Each individual may have slightly different coverage yield distributions across the exome. Clinical sensitivities and specificities of any individual exome are not calculated. Rare variants at the probe target site may affect analytical sensitivity.

Exome sequencing is limited in detecting the following types of mutations (this list might not be exhaustive):

  • large rearrangements
  • copy number variation mutations (large deletions/duplications)
  • mitochondrial genome mutations
  • epigenetic factors
  • mosaic mutations
  • uniparental disomy
  • mutations in repetitive or high GC rich regions
  • mutations in genes with corresponding pseudogenes or other highly homologous sequences