When Germline Genetic Testing Results Are Unclear: Highlighting Variants of Uncertain Significance

Abstract

With the advent of high-throughput next-generation sequencing (NGS) and multigene panel testing, genetic testing and interpretations have become increasingly complex. Specifically, reports demonstrating “variant of uncertain significance” (VUS) present interpretative challenges. Misinterpretation of a VUS may result in clinical harm, emotional distress for patients and family members, and potential health-care provider liability. The following article and deidentified case study illustrate how a lack of health-care provider and patient understanding of a germline VUS resulted in a negative patient outcome and unnecessary surgery.