How variants of uncertain significance affect clinical decisions: A systematic review.

Abstract

To assess the extent to which variants of uncertain significance (VUS) affect clinical decisions. We conducted a systematic review of studies reporting the impact of VUS on clinical decisions. We extracted quantitative data on VUS' impact for grouped analysis. We calculated and compared odds ratios of the specified decisions for patients found to have benign results, VUS, and pathogenic results. We included 45 articles in our overall review and 21 in our quantitative analysis. The overall review (n = 45) showed that VUS affect at least some care decision in 67% of studies. The quantitative analysis (n = 21) suggested that this impact clusters into 3 descriptive patterns, where VUS were treated as (1) benign, (2) "weak positives," or (3) pathogenic. VUS more commonly affect clinical decisions if studies were in fields outside of oncology, were prospective, reported clinician-centered versus patient-centered decisions, and reported screening versus definitive care decisions. Despite being limited by the small, heterogeneous studies included, this analysis suggests that VUS affect at least some clinical decision in a majority of reports.