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What is exome sequencing?
With exome analysis we can identify a genetic diagnosis in rare disease.
More about Exome sequencingWhat is exome sequencing?
Rather than be limited to analyzing single genes, exome analysis is aimed to cover the human exome, the coding region of all (20000) human genes. The technique that is used to cover the human exome can be Whole Exome Sequencing (WES) or Whole Genome Sequencing (WGS). All types of variants are potentially detectable by these assay. Due to this, exome analysis has proven to be a diagnostic test with a very high diagnostic yield.
Advantages of exome sequencing:
- The diagnostic yield of exome analysis is higher than achieved by Sanger sequencing
- Exome analysis can solve complex clinical cases
- Exome analysis can lead to a quicker genetic diagnosis
Our exome analysis approach:
Exome analysis is implemented in our Genome Diagnostics laboratory, in close collaboration with clinicians, clinical laboratory geneticists and scientists.
Our Exome analysis consists of 3 major steps:
- Whole exome or Genome Sequencing
- Exome Data Analysis
- Clinical Interpretation & Reporting
Clinical interpretation & reporting
There are several possible outcomes.
More about Clinical interpretation & reportingClinical interpretation & reporting
The variants identified will be interpreted in the clinical context provided by the referring clinicians.
There are several possible outcomes:
- One or more pathogenic variants are identified that may explain the disorder of the patient
- One or more variants are identified of wich the significance is not immediately clear; additional testing in family members, or other (biochemical) testing, may be required
- No variants are identified that might explain the disorder; after a gene panel analysis, an exome-wide analysis can be considered
The initial analysis is focused on known or predicted deleterious variants in genes known to be associated with the disorder the patient was referred for (analysis of one or more exome gene panels). However, if no causative variant is found within the gene panel, we can proceed with the analysis of the rest of the exome data. The interpretation in the exome-wide analysis is focused on likely-disruptive variants in all genes.
Besides the identification of causative variants in disease genes not (yet) suggested in a particular patient (broadening the phenotype) or the identification of novel (candidate) disease genes, exome-wide analysis does bear the risk of the identification of medically relevant variants for other (late onset) disorders; for example a variant associated with an increased cancer risk. These so called unsolicited findings could have important consequences for the patient and/or other family members. The risk of such unsolicited findings is reduced by variant filtering using gene panels or trio analysis.
Unsolicited findings will be discussed by a dedicated committee, which determines the clinical relevance. In general, the committee decides only to report (likely) pathogenic variants indicative of a treatable or preventable health problem, when it is regarded to be in the counselee's best interest to be informed.
In all situations, the patient will be informed of the results of exome analysis by their physician.
Information for referrers
Exome panels
Please visit our ordering website to view the panels we currently offer as well as the previous versions of these panels.
To view our policy on disclosing incidental findings click here.
Questions? Send an e-mail to: gen@radboudumc.nl
