Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Balancing uncertainty with patient autonomy in precision medicine

By the nature of their unknown pathogenicity, variants of unknown significance (VUS) should not inform clinical decisions for genetic carrier testing; nevertheless, VUS are increasingly returned to patients. We argue that the benefits of returning VUS to patients are outweighed by the potential for individual and health-care system-level harm.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. Hunter, D. J. Uncertainty in the era of precision medicine. N. Engl. J. Med. 375, 711–713 (2016).

    Article  Google Scholar 

  2. Makhnoon, S. et al. Experiences of patients seeking to participate in variant of uncertain significance reclassification research. J. Community Genet. (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Welsh, J. L. et al. Clinical decision-making in patients with variant of uncertain significance in BRCA1 or BRCA2 genes. Ann. Surg. Oncol. 24, 3067–3072 (2017).

    Article  Google Scholar 

  4. Richards, S. et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 17, 405–423 (2015).

    Article  Google Scholar 

  5. Wynn, J. et al. Clinical providers’ experiences with returning results from genomic sequencing: an interview study. BMC Med. Genomics 11, 45 (2018).

    Article  Google Scholar 

  6. Elwyn, G., Cochran, N. & Pignone, M. Shared decision making — the importance of diagnosing preferences. JAMA Intern. Med. 177, 1239–1240 (2017).

    Article  Google Scholar 

  7. Knight, F. H. Risk, Uncertainty and Profit (Hart, Schaffner & Marx, NY, 1921).

    Google Scholar 

  8. Regier, D. A. et al. Societal preferences for the return of incidental findings from clinical genomic sequencing: a discrete-choice experiment. CMAJ 187, E190–E197 (2015).

    Article  Google Scholar 

Download references


The authors thank C. McCabe for his valuable feedback on the development of this comment. They acknowledge support from the Canadian Institutes of Health Research (PCG-155555) and from Genome British Columbia’s Societal Issues Grant (SOC001). The Canadian Centre for Applied Research in Cancer Control (ARCC) is funded by Canadian Cancer Society Grant no. 2015-703549.

Author information

Authors and Affiliations



S.P. and D.A.R. researched the literature and wrote the article. All authors provided substantial contributions to discussions of the content and reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Dean A. Regier.

Ethics declarations

Competing interests

D.A.R. has received travel support from Illumina to attend conferences in Boston, USA, and Barcelona, Spain. S.P. and S.S. declare no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Pollard, S., Sun, S. & Regier, D.A. Balancing uncertainty with patient autonomy in precision medicine. Nat Rev Genet 20, 251–252 (2019).

Download citation

  • Published:

  • Issue Date:

  • DOI:

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing