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. Variants of unknown significance (VUS) are genetic variants whose association with disease risk is unknown. The authors posit that VUS should not inform clinical decision-making as the benefits of returning this genetic information to patients undergoing genetic testing are outweighed by the potential for harm.