This $172,584 Project Grant award from the National Human Genome Research Institute (CFDA 93.172 - Human Genome Research) supports a research initiative led by Vanderbilt University Medical Center (VUMC) to develop new methods for reclassifying genetic variants of uncertain significance. The project aims to leverage large biobank datasets and high-throughput functional assays to generate evidence to improve the clinical interpretation of cardiovascular disease-associated genetic variants. Key deliverables include developing phenotype risk scores to amplify rare variant signals in biobank records, and deploying these scores with multiplexed variant effect assays to prospectively reclassify variants currently categorized as uncertain. This work is expected to accelerate the implementation of genomic medicine by providing clinicians with more definitive genetic diagnoses. The grant was awarded on January 3, 2025 with an anticipated completion date of December 31, 2029.