Impact of Multigene Panel Testing in High-Risk Uveal Melanoma Patients

Germline genetic testing is increasingly incorporated into the care of patients with uveal melanoma, yet optimal testing strategies remain unclear. This study aimed to evaluate the outcome of germline clinical genetic testing in uveal melanoma (UM) patients who met the National Comprehensive Cancer Network (NCCN) guidelines for genetic testing. A retrospective chart review was conducted on UM patients seen in The Ohio State University Cancer Genetics Clinic between 5/1/2021 and 9/19/2025. Seventy individuals underwent clinical genetic testing, primarily via large multigene panels. Ten UM patients, including two related individuals, had pathogenic or likely pathogenic (P/LP) variants in known cancer genes (BAP1, BRCA1, BRCA2, MBD4, MUTYH, POT1, XRCC2). Among unrelated individuals, the positive rate was 13% (8/69). Excluding carrier genes, the rate was 10.1% (7/69). Eight patients would have been missed if only tested for BAP1 per American Society of Clinical Oncology (ASCO) 2024 recommendations. There was no association between tumor size, stage, and germline P/LP variants. In summary, NCCN guidelines are useful in the prioritization of UM patients for genetic testing. Additionally, these findings support genetic counseling for multigene panel testing in high-risk uveal melanoma patients. Further studies of the impact of germline variants on UM disease outcome are warranted.