Exome — the protein-coding portion of the genome

Content and scale

Although the exome contains the protein-coding portions of genes, it represents only a small fraction of the entire genome; in humans it is commonly estimated to cover roughly one to a few percent of total genomic DNA. Because many disease-causing variants alter amino acid sequences or create premature stop codons, the exome is highly enriched for changes that directly affect protein structure and function.

Types of variants found in the exome

• Missense variants that change one amino acid to another.
• Nonsense variants that introduce premature stop codons and truncate proteins.
• Frameshift insertions or deletions that alter the reading frame.
• Variants affecting canonical splice sites and nearby sequences that can disrupt exon inclusion.

Sequencing and applications

Exome sequencing uses targeted capture or enrichment methods to isolate exonic DNA before high-throughput sequencing. This approach is cost‑effective compared with whole-genome sequencing for many clinical and research questions because it focuses on regions with clearer functional interpretation. Exome analysis is widely used to discover genes responsible for Mendelian disorders, to assist clinical diagnosis, and to study how protein-coding variation contributes to traits and disease risk.

Interpretation and resources

Interpreting exome variants requires careful assessment of predicted effect on protein function, population frequency, inheritance pattern and supporting evidence from functional studies. Public variant repositories and annotation resources help prioritize likely pathogenic changes; information about coding sequences and protein impact is routinely consulted during evaluation (protein-coding sequences).

Limitations and considerations

Exome-focused approaches do not capture most noncoding regulatory regions, structural variants outside targeted exons, or all splice regulatory elements. Coverage may be uneven, some exons are difficult to sequence, and variants in poorly annotated exons can be missed. For comprehensive discovery, whole-genome sequencing or complementary assays may be required. Ethical considerations, such as return of incidental findings and variant uncertainty, are important when exome data are used clinically or in research.