Genetic testing has become a powerful diagnostic tool in many aspects of medical practice. It can provide information regarding the genetic etiology for individuals manifesting symptoms, inform carrier status and recurrence risk for genetic disorders, enable population-based screening for disease risk, and guide therapy to optimize outcome and avoid adverse treatment sequelae. Although guidelines have been established for the classification of sequence and structural variants into categories including pathogenic (P), likely pathogenic (LP), uncertain significance (VUS), likely benign (LB), and benign (B),1,2 limited professional guidance has been put forth on when to report VUS and whether it should vary based on specific types of tests and indications.