How a GUS can fly: Triaging genes of uncertain significance in a clinical laboratory setting

Genome sequencing (GS) has facilitated the discovery of new gene-phenotype associations. While these discoveries typically occur in a research setting, clinical laboratories may encounter variants of interest in otherwise negative cases. Variant classification guidelines from ACMG/AMP allow for reporting of variants in genes of uncertain significance (GUSs); however, these variants should always be classified as “uncertain significance” with modification of evidence code usage. Here, we discuss our laboratory’s approach to evaluating the relevance of variants in GUSs in a clinical laboratory setting, and highlight the need for a uniform policy for inclusion on lab reports.