A pathogenic variant is a mutation with direct consequences to human health. A pathogenic variant can be considered “actionable” if the condition resulting from the pathogenic mutation is treatable or “nonactionable” if the condition is untreatable. A genome has a 1—5% chance of harbouring a pathogenic variant that has a health implication.1-3
In the unlikely event that the subject’s genome sequence analysis reveals a pathogenic variant (actionable or nonactionable), the client has an option of having the genetic information verified with additional technologies to ascertain that it is accurate. Validation makes the genome sequence clinically valid and therefore available for medical interpretation toward potential treatment (if the discovered pathogen is actionable). Choice of the validation option will generate an additional Analysis Report specifically tailored for health care professionals, which includes a statement describing the information that was discovered, how the information was obtained, proof of the validated sequence, and the identity of the institution responsible for the information generated.
The information that a verified pathogenic variant was located in the genome sequence can be shared with a medical doctor who will integrate this information with the client’s personal and family medical history and suggest appropriate surveillance or treatment. Confirmation with secondary technology is necessary prior to consultation with a medical professional to rule out a potential technical anomaly.
The client can obtain pathogenic variant verification information in one of the following ways.
1) Pathogenic variant verification can be performed immediately in the laboratory where the genome sequence data were produced, using the same sample that was used for genome sequence data generation. This service is delivered only if it was prepurchased when the genome sequencing procedure was paid for.
2) If pathogenic variant verification was not prepurchased when the genome sequencing procedure was paid for, the client can request and pay for data verification within the time period that the tissue sample is maintained by the sequencing laboratory.
3) The client can send a new tissue sample to the laboratory where the genome sequence data were produced and request pathogenic variant verification, or the client can request pathogenic variant verification from another laboratory.
Pathogenic variant verification is billed per single mutation.
- Dorschner MO, et al. 2013. Actionable, pathogenic incidental findings in 1,000 participants' exomes. Am J Hum Genet 93(4): 631-40
- Gambin T, et al. 2015. Secondary findings and carrier test frequencies in a large multiethnic sample. Genome Med 7(1): 54
- Olfson E, et al. 2015. Identification of Medically Actionable Secondary Findings in the 1000 Genomes. PLoS One 10(9): e0135193