Genetic testing has transformed the diagnosis of hereditary cancer syndromes, but many DNA variants remain difficult to interpret because their biological effects are unknown. This uncertainty can complicate genetic counselling and clinical management. We developed a rapid functional test to experimentally determine whether suspected variants disrupt RNA splicing, the process by which RNA is edited before being used to make proteins. Our optimized minigene assay clarified the effects of several previously unresolved variants and improved their clinical classification. Importantly, the test does not require patient-derived RNA and is compatible with routine diagnostic timelines, providing laboratories with a practical approach to support more informed decisions for patients and their families. (https://jmg.bmj.com/content/early/2026/08/24/jmg-2026-111675)