Navigating variants of uncertain significance in genetic dyslipidemia: how to assess and counsel patients.

Abstract

Purpose of review: Genetic testing has become an integral component of clinical care when an inherited condition is suspected. However, the interpretation of variants identified with this testing can be nuanced. Variants of uncertain significance (VUS) are variants for which there is not enough data currently available to determine if the variant is causal for disease (i.e. pathogenic) or is benign. VUS can exist on a spectrum with some leaning towards suspected pathogenicity and others leaning towards likely benign. Clinician understanding of variant interpretation can improve clinical care by providing more context around how suspicious a VUS is, determining whether additional steps should be taken to further evaluate the variant in question, and ensuring patient understanding of these results.

Recent findings: Research on this topic highlights the complexities around VUS interpretation and counseling. VUS are not static: interpretations of pathogenicity change as new information is uncovered.

Summary: This review aims to summarize this literature and provide insight into variant interpretation, practical steps clinicians can take to further assess a VUS, and considerations when counseling patients on these results.