Clinical Exome Sequencing

Clinical Exome Sequencing (CES), Often referred to as next-generation sequencing (NGS) for protein-coding genes, Clinical Exome Sequencing (CES) has increasingly become a reliable diagnostic method for identifying unexplained genetic disorders, rare inherited conditions, and other undiagnosed medical syndromes.

Therefore, when symptoms fail to indicate a specific diagnosis, Clinical Exome Sequencing serves as a powerful genomic tool for genetic evaluation. In such cases, Clinical Exome Sequencing allows healthcare professionals like clinical geneticists, molecular pathologists, or genomics specialists to closely examine an individual’s DNA and genetic makeup.

How is a Clinical Exome Sequencing test done?

A single test, Clinical Exome Sequencing, offers the remarkable ability to detect many genetic disorders. Furthermore, this comprehensive testing approach enables healthcare professionals to identify a wide range of genetic variations and mutations.

What Is Clinical Exome Sequencing?

The Clinical Exome Sequencing (CES) test identifies disease-causing DNA variants within the 1% of the genome that codes for proteins (exons) or flanks the regions that code for proteins (splice junctions). The DNA sequence contains thousands of genes, but not all regions contribute equally to the development of genetic disorders. The exome refers to the small portion of the human genome, about 1 to 2%, that includes protein-coding genes or functional DNA sequences essential for cellular function.

Clinical Exome Sequencing (CES) is a molecular diagnostic test that focuses specifically on these protein-coding regions to detect inherited mutations, genomic variants, or genetic abnormalities linked to an individual’s health condition. It’s similar to scanning only the key pages of a genetic blueprint or instruction manual to find errors that impact how the body functions—making CES a valuable tool in the field of precision medicine, rare disease diagnosis, and genetic screening.

What is the purpose of Clinical Exome Sequencing?

Clinical Exome Sequencing (CES) is a specialized genetic test used to identify disease-causing mutations within the exons the coding regions of the genome and their nearby splice sites. Although these regions make up just about 1% of our DNA, they contain the majority of known mutations responsible for genetic disorders.

Clinical Exome Sequencing (CES) is designed to analyze the protein-coding regions of the genome to identify genetic variations that may cause inherited disorders or complex medical conditions. The main purpose of CES is to help healthcare providers and patients understand the genetic basis of diseases, enabling accurate diagnosis, personalized treatment planning, and informed decisions regarding management and preventive care. At My Genetic DNA Center, CES is performed using advanced sequencing technology and expert analysis to provide reliable, actionable results that guide clinical and personal healthcare decisions.

Indications for Clinical Exome sequencing Test:

When clinical symptoms or a family history point to a possible genetic cause.
To evaluate diseases known to have diverse genetic origins.
In cases where a patient presents with symptoms of an unidentified genetic condition (diagnostic odyssey).
To support decisions related to medical treatment and management.
To verify a suspected diagnosis with a genetic basis.
To inform reproductive choices and assess the likelihood of recurrence in future pregnancies.

Why Focus on the Exome?

While whole genome sequencing provides a broader view of the entire genome, it is more expensive and time-consuming. CES provides a high-yield, cost-effective alternative by concentrating on the portions of DNA most likely to carry clinically relevant mutations. This focus makes CES particularly useful when time and resources are limited.

When Is Clinical exome Recommended?

Clinical Exome Sequencing(CES) is often recommended when:

A patient presents with unexplained developmental delays, intellectual disabilities, or growth abnormalities.
Neurological symptoms, such as seizures or movement disorders, lack a clear cause.
Multiple congenital anomalies are observed without a confirmed diagnosis.
There is a known or suspected family history of genetic disorders.
Previous genetic testing (e.g., gene panels or chromosomal microarrays) has been inconclusive.

Why Choose Clinical Exome Sequencing test?

Thorough and Accurate Analysis: Offers a reliable way to examine DNA for identifying the underlying genetic cause of various diseases or developmental conditions.
Broad Clinical Application: Suitable for detecting mutations in autosomal dominant, autosomal recessive, and X-linked inherited disorders.
Cost-Effective Solution: Especially beneficial for diagnosing conditions with complex or overlapping clinical features, reducing the need for multiple tests.
Clinically Actionable Reporting: Identifies gene mutations associated with diseases, referencing trusted databases like OMIM and HGMD.
Detection of Known and Novel Variants: Capable of recognizing both previously reported mutations and new, potentially disease-causing changes.

How Does the clinical exome test Work?

The Clinical Exome Test analyzes the protein-coding regions of a person’s genome to identify genetic variations that may be linked to inherited disorders or medical conditions. The process begins with the collection of a blood or saliva sample, from which high-quality DNA is extracted. Using advanced sequencing technology, the exome—the regions that encode proteins—is read in detail. Bioinformatics tools then analyze the sequencing data to detect significant genetic variants. Finally, genetic experts interpret the findings and prepare a comprehensive report.

At My Genetic DNA Center, we ensure that every step, from sample collection to report generation, follows strict quality standards to deliver accurate, reliable, and confidential results.

Key Features of Clinical Exome Test:

Comprehensive Gene Coverage: Targets a wide range of genes associated with human diseases, including 4,468 genes from OMIM (as of October 2019), 2,937 from ClinVar (September 2019), 4,860 from HGMD (version 2019.2), 3,931 from Orphanet, 4,217 from HPO, and 59 genes recommended by ACMG for incidental findings.
Extensive Pathogenic Variant Inclusion: Includes a large number of known pathogenic and likely pathogenic mutations—such as 184,632 from HGMD, 70,703 from ClinVar, and 10,120 novel variants identified through over 50,000 clinical reports.
Detection of Non-Coding Variants: Captures disease-causing mutations in deep intronic and promoter regions, including 2,170 variants from HGMD and 13,037 from ClinVar.
Enhanced CNV Analysis: Incorporates additional probes in intronic regions of 668 genes to improve the identification of copy number variations related to Mendelian disorders, supported by published studies and internal clinical data.
Multi-Transcript Design: Utilizes probe sets designed using multiple gene transcripts to ensure broader and more accurate detection.
Mitochondrial Genome Coverage: Includes all 37 mitochondrial genes to support diagnosis of mitochondrial disorders.

How accurate is clinical exome sequencing?

On average, we achieve a capture and sequencing rate of >99.4% of the exome, ensuring reliable variant calls. Additionally, coverage is determined by the number of times each nucleotide is sequenced.

Benefits of Clinical Exome Sequencing:

Accurate Diagnosis of Genetic Conditions : Clinical Exome Sequencing helps identify the underlying genetic cause of unexplained symptoms. By focusing on the protein-coding regions of DNA, CES increases the chances of detecting mutations linked to various inherited disorders.
Saves Time and Reduces Diagnostic Burden : Instead of undergoing multiple unrelated tests, CES streamlines the diagnostic process. It often leads to quicker results, reducing the time spent in uncertainty and minimizing unnecessary procedures.
Supports Precision Medicine : CES enables personalized healthcare by identifying specific genetic changes that may affect treatment. This allows doctors to develop tailored management plans based on an individual’s unique genetic profile.
Informs Family Planning and Risk Assessment : CES results help families understand genetic inheritance and the risk of passing conditions to future generations. This is especially helpful in making informed reproductive choices.

Limitations of Clinical Exome Sequencing

It may miss mutations outside the exome, such as in regulatory or intronic regions.
Variants of Uncertain Significance (VUS) may be detected, requiring ongoing research to interpret.
Clinicians may identify incidental findings unrelated to the tested condition, which can raise ethical concerns.
Not all mutations can currently be linked to known diseases due to limitations in medical knowledge.

Clinical exome Sequencing vs. Other Genetic Tests

Gene Panels : These tests analyze a preselected group of genes related to a specific condition. While faster and more targeted, they may miss unexpected mutations that CES could detect.

Whole Genome Sequencing (WGS) : This method sequences all of a person’s DNA, including non-coding regions. It provides comprehensive data but is more expensive and generates more complex results.

CES stands as a balanced approach : offering more breadth than panels and more affordability and focus than WGS.

Real-World Applications of Clinical exome Sequencing

Clinical Exome Sequencing has helped diagnose conditions like:

Rare metabolic disorders (e.g., mitochondrial diseases)
Inherited forms of epilepsy
Congenital hearing loss or blindness
Skeletal dysplasias
Immunodeficiency syndromes

How long does it take to receive the results?

The results are typically available within 4 to 5 weeks. Once the analysis is complete, the report will be delivered to your registered email address.

Conclusion:

Clinical Exome Sequencing represents a revolution in diagnostic genetics. By concentrating on the most vital regions of our DNA, it bridges the gap between undiagnosed symptoms and precise, actionable answers. For many patients and families navigating uncertainty, CES offers not only a diagnosis but also a path forward—toward better understanding, management, and hope.