This test aims to detect all clinically relevant variants within the genes analyzed related to the indication for testing. The majority of these genes are assessed for variants within all regions of a gene that encode a protein (also called ‘exons’), as well as adjacent regions that do not encode a protein (also called ‘introns’).
Other types of genetic variation cannot be detected with this test, for example complex rearrangements such as translocations, or chromosomal aneuploidy. This test does not reliably detect mosaicism. The sensitivity for detecting deletions of maximum 200 base pairs, as well as insertions that overlap less than 200 base pairs of contiguous coding sequence is limited. The detection sensitivity can be decreased by the presence of large insertions that might interfere with the chemistry used for targeting genes of interest. The identity and sequence of large insertions might also not be completely resolved. Regions of low/high GC content, homopolymers, and simple sequence repeats limit the sensitivity to detect variants.
Probably Genetic only reports on findings within the genes that are covered by whole exome sequencing. It is important to understand that there may be variants in those genes that current technology is not able to detect. Additionally, there may be genes associated with the patient’s symptoms whose clinical association has not yet been definitively established. Positive results do not imply that there are no other contributions, genetic or otherwise, to the patient’s phenotype. The test may therefore not detect all variants that are relevant for the patient. Furthermore, in the event that a variant is detected that is associated with a disorder other than your phenotype, this information will not be included in the report. For example, if the test was ordered due to a neurodevelopmental condition the patient is affected by, but the patient also carries a different variant associated with an elevated risk of cancer, the cancer-associated variant will not be included in this report. Genetic counseling and/or physician consultation way be warranted to ensure complete understanding of the test results.
In rare circumstances, the presence of somatic or donor variants can complicate germline DNA analysis, for example due to circulating hematolymphoid neoplasms, a recent blood transfusion, or an allogeneic bone marrow transplant. Recent chemotherapy treatments may also affect the patient’s DNA sample quality.
Importantly, a genetic test cannot diagnose conditions which are typically diagnosed by clinical observation. For example, a genetic test cannot confirm the diagnosis or presence of autism spectrum disorder, intellectual disability, or developmental delay in an individual. While a genetic test can increase the suspicion of some of these symptoms, a clinical evaluation may still be required for confirmation.
Does the test have limitations?
