Only about 1 to 2% of the human genome codes for proteins; this part is called the exome. Since the great majority of known disease-causing variants lie in the exome, whole exome sequencing (WES) allows thousands of genes to be examined at once in a single test.
When is it considered?
- Cases whose clinical findings overlap with several genetic diseases and cannot be directed to a single test
- Unexplained developmental delay, neuromuscular or multisystem involvement
- Undiagnosed patients whose targeted tests (panel, single gene) have come back negative
Interpretation and family analysis
Because WES data are extensive, results are evaluated together with the patient's clinical findings. Where possible, testing alongside samples from both parents (trio analysis) makes it easier to determine how a variant is inherited and to detect newly arising (de novo) changes. In some cases no diagnosis is reached at the first analysis; re-evaluating the data later ("reanalysis") can increase the diagnostic rate.
