Abstract
Patients’ understanding of a genetic variant of unknown clinical significance (VUS) is likely to influence beliefs about risk implications, consequent medical decisions, and other actions such as involvement in research. We interviewed 26 self-selected participants with a clinically identified VUS before they enrolled into a VUS reclassification study. Semi-structured interviews addressed topics including motivation to get genetic test, experience with the VUS result, affective responses to receiving VUS, and perceived effect of VUS and reclassification on medical care. We found that family and personal history of disease were the most prevalent motivators for getting a genetic test. Participants demonstrated mixed understanding of VUS. Most expressed negative effect on learning of their VUS result and uncertainty about its impact on clinical management. Most expected reclassification efforts to benefit their family members but not themselves. Some expressed distrust of their providers following a VUS result. Participation in the VUS reclassification study appeared to be motivated by four factors for patients with VUS—negative effect about VUS, uncertainty about its impact on clinical management, concern for family members’ well-being, and to advance science. Perhaps the direct acknowledgement and appraisal of uncertainty as a means of coping was missing in some pre-test counseling experienced by our participants and thus they were not psychologically prepared for atypical VUS results. The finding of VUS-induced provider distrust suggests a need for careful consideration of appropriate pre- and post-test counseling about VUS.
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Funding
This study was funded by in part by the Damon Runyon Cancer Research Foundation (DRR-33-15), the National Human Genome Research Institute (R21HG008513), and the Fred Hutch/University of Washington Cancer Consortium (NCI 5P30 CA015704-39).
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Makhnoon, S., Garrett, L.T., Burke, W. et al. Experiences of patients seeking to participate in variant of uncertain significance reclassification research. J Community Genet 10, 189–196 (2019). https://doi.org/10.1007/s12687-018-0375-3
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DOI: https://doi.org/10.1007/s12687-018-0375-3