Author: Daphne Chen, MS CGC
Variants of uncertain significance (VUS) are reported in a minority of hereditary cancer panel test results. These VUS’s are continually evaluated through Myriad’s Variant Classification Program for potential reclassification based on new scientific publications, validated statistical algorithms, and other robust classification tools.
Gene variants can impact the production and function of proteins through disruption of RNA splicing, a naturally-occurring and important cellular process. Although variants that impact RNA splicing account for only a fraction of all pathogenic variants related to hereditary cancer predisposition, identification and accurate classification of these variants ensure appropriate clinical care for at-risk patients.
In 2015, Myriad launched an in-house RNA analysis laboratory to aid in the classification of variants identified through clinical hereditary cancer testing. Variants that do not impact RNA splicing are classified using other classification tools. However, variants that have the potential to impact RNA splicing are thoroughly evaluated and follow an IRB-approved research protocol for further RNA analysis. A member of the Variant Specialist team and a licensed and certified genetic counselor contacts the healthcare provider and patient to obtain verbal consent for the RNA analysis and to coordinate submission of an additional blood sample. Once the variant has been analyzed in the lab, the RNA splicing data is reviewed by the Variant Reclassification team, in the context of any additional literature, clinical data, or other scientific evidence that may be relevant to the variant. If RNA analysis leads to the reclassification of a variant, any patients carrying the reclassified variant will receive an amended report.
As part of Myriad’s lifetime commitment to providing the most accurate and up-to-date genetic information for their patients, these RNA studies are performed at no additional cost to the patient. In addition, Myriad is continuously developing and improving other novel classification tools to aid in the reclassification of variants, many of which do not affect RNA splicing and cannot be reclassified through RNA analysis alone. Genetics is a constantly evolving field, and Myriad is excited to continue exploring the role of RNA analysis in hereditary cancer testing and in being able to provide accurate and clinically important information for patients.