Clinical exome sequencing uses a technology called Next Generation Sequencing (NGS). It allows the analysis of thousands of genes at the same time which allows for the identification of genetic changes that may cause a hereditary condition. A clinical exome can be very useful if you have a medical condition which may be caused by one or more gene changes and when it’s not clear exactly which gene the change is in.
How is the clinical exome interpreted?
The most complex part of the clinical exome is in the interpretation of results. This is because not all genetic changes (variants) cause genetic conditions. Some variants are a normal part of what makes everyone different. Variants may be inherited from ancestors, or may be new in an individual (not inherited). Some are known to cause genetic conditions, and for some we don’t understand their significance. A clinical exome test usually identifies hundreds of variants in any one individual. A team of experts including doctors, genetic counsellors and laboratory scientists then work together to understand the significance of each variant found and how this might relate to a patient’s condition.
Bioinformatics criteria for Exome sequencing analysis
Variants obtained from sequencing were filtered to include only novel/rare (MAF=0.01%), functional (predicted damaging by SIFT/Polyphen), present in the relevant zygosity state in the affected individuals.
What level of clinical exome test to order
The basic level is sufficient for the detection of genetic changes responsible for a diagnosed syndrome. However, when more than one diagnosis is likely, then it is recommended to choose the Expanded or Whole-exome sequencing options. If there is no diagnosis for the observed condition then the most suitable option will be Trio (affected as well as parents) whole exome sequencing.