6533 Background: Today’s oncologist is responsible for choosing appropriate cancer genomics tests to inform patient treatment from multiple available platforms, weighing cost, availability, sensitivity and specificity, and clinical actionability. Knowledge-driven clinical decision support tools can assist clinicians in choosing the panel that is most informative in a given clinical space. Methods: Using a queryable knowledgebase of >1800 active clinical trials containing structured eligibility criteria curations for diagnosis and genomic alterations, we compared two CLIA-regulated genomic panels for clinical actionability over the landscape of solid, breast, and lung cancer clinical trials. Results: The larger panel (73 genes) was more actionable than the smaller panel (62 genes) in the breast cancer (10x more trials returned) and solid tumor (2.7x more trials returned) clinical trial space, while the smaller panel returned 1.2x more trials in the lung cancer space (see table). Conclusions: This analysis demonstrates that patient diagnosis has a significant effect on the potential clinical actionability of a given genomic panel. Further, this analysis demonstrates the clinical utility of knowledge-driven clinical decision support tools for test selection, especially given the often-limited tumor sample available, cost of genomic panel testing, and continuously shifting trial landscape. [Table: see text]