A new ACMG Points-to-Consider article provides advice for clinicians and genetic testing labs regarding reporting of Variants of Uncertain Significance (VUS) to better balance the potential benefits and harms of reporting such variants, offer suggestions for following up on genetic test reports, and consider adopting VUS subclasses and updating reports when variant classifications change. They outlined that all VUS results are not equal! Thus, they suggested a subcategorization system which included: VUS-low (lowest concern), VUS-mid (uncertain), and VUS-high (higher concern). They also suggested VUS results should be reported in symptomatic genetic testing when results relate to the patient’s condition. On the flip side, they suggested not to report a VUS in population/screening testing for disease risk. This matters because over 90% of clinicians, genetic counselors, lab directors, AND patients surveyed agree that clearer reporting helps guide better follow-up care. This guidance helps labs prioritize which variants are most likely to explain a patient’s symptoms and reduce unnecessary follow-up on unlikely findings. We expect that an updated sequence variant classification standard (SVC v4.0) will come out soon, to make this approach standard across all genetic testing labs. These recommendations put patients first—ensuring results are clear, actionable, and personalized to individual cases.
Mighton, et al. Genet Med. 2026:102583. PMID: 42287277. Article: https://pubmed.ncbi.nlm.nih.gov/42287277/. Social media post: https://inheritedcancer.net/post070726/