Whole Exome Sequencing: A Complete Guide for Patients & Clinicians

What Is Whole Exome Sequencing?

Whole Exome Sequencing (WES) is a genomic technique that sequences all protein-coding regions (exons) of an individual’s DNA—about 1–2% of the genome—where most disease-causing mutations reside . By targeting exomes, WES efficiently identifies genetic variants linked to both rare Mendelian disorders and common conditions, without the higher expense and data complexity of sequencing the entire genome 

What Is Whole Exome Sequencing Used For?

• Diagnostic testing in individuals with undiagnosed genetic disorders
  
• Identifying de novo mutations in trio-based studies (child + parents
  
• Research into neurodevelopmental, oncologic, and rare diseases
  
• Assessing incidental or secondary findings, which may impact health beyond the original testing purpose medlineplus.gov
  

Whole Genome vs Whole Exome Sequencing

Feature	Whole Exome Sequencing (WES)	Whole Genome Sequencing (WGS)
Coverage	~30 million bp (~1–2% of DNA)	~3 billion bp (entire genome)
Data volume	~10 GB per sample	~90 GB per sample
Cost	Generally simpler and cheaper	Higher, but narrowing as sequencing costs drop
Diagnostic yield	High for coding-region diseases, cost-effective	Broader detection including non-coding and structural variants
Use case	Ideal for suspected Mendelian disorders, clinical labs	Great for comprehensive research or cases where previous tests were inconclusive

Whole Exome Sequencing Cost

The cost of WES varies widely:

• Range per singleton test: $555–$5,169 USD
  
• Examples from academic labs: $856–$2,110 depending on coverage depth (100×–500×) mdanderson.org
  
• Consumer rates: starting around $499–$999, though interpretation and counseling may cost extra wired.com
  

Why Choose WES Over WGS (Or Vice Versa)?

• WES is ideal when you want:
  
  • A cost-effective test focused on disease-causing exons
    
  • Faster analysis with smaller data sets
    
  • High diagnostic yield for known coding-region disorders
    
• WGS is best when:
  
  • Non-coding regions, structural variants, or regulatory elements might be involved
    
  • You’ve previously had a negative WES but suspect genomic causes
    
  • You need the most comprehensive genomic profile, knowing costs are higher
    

Seq Genetics: The Clinical Sequencing Process

The typical exome testing pipeline involves:

1. Extracting DNA from blood or saliva.
   
2. Capturing exons using hybridization methods.
   
3. Next-gen sequencing (e.g., Illumina platform).
   
4. Bioinformatic analysis to detect variants.
   
5. Clinical interpretation and genetic counseling
   

These steps ensure results are meaningful and understandable in a clinical context.

Points to Watch: Limitations & Considerations

• WES misses non-coding, intronic, and structural variants—WGS covers them
  
• Data interpretation can reveal secondary findings, so pre-test counseling is crucial medlineplus.gov
  
• Data storage and ethical/privacy concerns must be addressed
  

Summary: What You Should Know About Exome Testing

• What is Whole Exome Sequencing: It sequences all coding regions, targeting where many disease-causing mutations lie.
  
• Whole Genome vs Exome Sequencing: WES is cheaper, faster, and sufficient for many clinical diagnoses; WGS offers broader coverage but is more expensive.
  
• Whole Exome Sequencing Cost: Ranges from $500–$5,000+, depending on lab, coverage, and interpretation services.
  
• Seq Genetics / Exome Testing Workflow: Involves lab processing, sequencing, bioinformatics, and clinical counseling.
  
• Limitations: Misses non-coding variants; may reveal unintended findings, so genetic counseling is recommended.
  

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Final Takeaway

Whole exome sequencing is a powerful, efficient, and increasingly accessible method for diagnosing genetic disorders by focusing on protein-coding regions. While it often strikes the right balance between cost and diagnostic yield, especially for suspected Mendelian conditions, whole genome sequencing offers the most comprehensive insight—and may be the better choice when prior testing falls short or non-coding regions are suspected contributors. Always consult with a genetics professional for tailored guidance.