Osteogenesis Imperfecta  (OI) is an important condition to diagnose early to ensure children are monitored and treated in a timely manner. Increased access to genetic testing has enabled more diagnosis but this can be complicated by ‘Variants of uncertain significance (VUS)’ which results in uncertainty. Using England’s national OI database, we undertook an iterative analysis of such variants allowing reclassification following updated guidelines. This work transformed uncertain genetic results into actionable clinical information. (https://jmg.bmj.com/content/early/2026/02/10/jmg-2025-111334 )

The Balasubramanian lab @ University of Sheffield is working on VUS in OI and other collagen-related disorders using functional assays to validate the pathogenicity of such variants.