New Guidance for Reporting Variants of Uncertain Significance in Genomics

The American College of Medical Genetics and Genomics (ACMG) has published a new statement, Points to Consider for the Reporting of Variants of Uncertain Significance in Germline Genetic and Genomic Testing, providing guidance to laboratories and healthcare professionals on the reporting and communication of variants of uncertain significance (VUS) identified through genetic and genomic testing.

VUS represent one of the most complex and frequently misunderstood aspects of genetic testing. A VUS is a genetic change for which there is currently insufficient evidence to determine whether it is associated with a disease. As genetic testing becomes increasingly integrated into patient care, consistent reporting and transparency in the interpretation of these findings are critical to supporting appropriate clinical decision-making and avoiding misinterpretation.

The statement addresses important considerations related to the classification, reporting, communication, and clinical use of VUS findings and emphasizes the importance of transparently delineating VUS into those variants more likely to be reclassified as benign (VUS-low) versus those for which a clinician may wish to expend more effort in follow-up (VUS-high).

For decades labs have developed their own policies around when and how to report VUS in clinical genetic testing, with limited guidance available that spans all platforms and clinical contexts. We are delighted to be able to provide consistent recommendations for laboratories that balance the benefits and risks of VUS reporting and allow transparency for patients and clinicians who are navigating this complexity."

Heidi Rehm, PhD, FACMG

Published in Genetics in Medicine, ACMG's official journal, the statement outlines key considerations and recommendations intended to promote clarity, consistency, and best practices in the reporting of VUS findings across clinical laboratories and healthcare settings.

"As the use of genetic and genomic testing continues to expand, clear guidance on the reporting of uncertain findings is essential," said ACMG President Mira B. Irons, MD, FACMG. "This statement reflects ACMG's ongoing commitment to supporting laboratories, clinicians, genetic counselors, and other healthcare professionals with evidence-based guidance that promotes high-quality patient care and the responsible use of genetic information."