Finding the appropriate panel for a patient can be highly difficult. Not every patient can be fitted into the neat phenotypic box or get the precise diagnosis for a particular genetic condition. Whole Exome Sequencing eradicates the challenge of finding the right panel or the need to make a customized panel. The test evaluates all protein-coding genes in a single test.
Whole Exome Sequencing Genetic Test is often selected for the patients who have complex phenotypes impacting several parts of the body systems. When a doctor suspect’s more than one disorder or the previous genetic testing has not yielded informative results or when the suspected disorder does not have a readily available genetic test, then a whole-exome sequencing test can come to your rescue.
Here are the important factors to consider when choosing a Whole-exome sequencing test for you or your family:
- A difference between 99% coverage and 97% coverage
As the WES technology is relatively new, and thus it is not possible to capture the whole 100 percent of the exome at high quality. But still, the technology is able to capture over more than 99.4 percent of the exome with a quality enabling reliable variant calls. The Whole Exome Sequencing provides good sequencing depth and good, uniform coverage.
You may assume that small percentage differences might not make a strong impact, but that’s where you are wrong. This can translate to big differences at the sequences levels as it may dilute the diagnostic impact. The differences between 99% coverage and 97% coverage can imply that hundreds of genes and thousands of exons are not being covered.
- Not every exome has known disease-causing deep intronic variants.
Genes are made up of more than just exons. Introns are known to carry approx. 15 percent of the disease-causing variants. Many of these are found in the exon-intron boundary. With the help of a whole exome sequencing test, geneticists can identify a hemizygous, likely pathogenic variant in the promoter region.
- CNV detection is possible with WES
The CNVs (copy number variations) are detected by the NGS platform, which is a crucial component of the high-quality exome analysis. In an inherited disorder, CNVs are an important disease mechanism that is evaluated in all patients having a genetic disorder. The Whole Exome Sequencing Genetic Test diagnoses from small deletions and duplications. CNVs can represent a significant portion of the identified disease-causing variants.
- The Phenotype approach filters the genes even before the first analysis.
Having high-quality sequencing data is important, but how that data is analyzed is also important. This enables the identification of atypical presentation of known genetic disorders in newly established genes. This is a powerful instrument in neonates and young children when their phenotype is not completely built.
- The candidates’ genes are included for diagnosis
In cases where the genes come out as a negative for a known disease and likely pathogenic variants or a part of the phenotype is explained, then the WES is useful to analyze and find out about the genes variants which are not yet known to cause or linked with disease.
