Abstract Body (Do not enter title and authors here): Hypertrophic cardiomyopathy (HCM), an inheritable cardiomyopathy characterized by idiopathic left ventricular hypertrophy, can cause sudden cardiac death or heart failure. Autosomal-dominant missense mutations in MYH7 (encoding the sarcomeric βMHC protein) account for ~33% of genotype-positive HCM cases. While pathogenic MYH7 variants are clinically actionable by dictating subsequent medical management, ~75% of MYH7 missense variants in ClinVar are variants of unknown significance (VUS). Gene-edited human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are useful tools to accurately determine the effect of MYH7 variants; however, hiPSC gene-editing is generally inefficient and low throughput. Thus, we leveraged a novel gene-editing method we previously developed called CRISPRa On-Target Editing Retrieval (CRaTER) which increases the success of gene-editing by 25-fold and enabled the generation of a MYH7 variant library in hiPSC-CMs with over 400 variants. Because deleterious mutations can reduce protein stability, we flow sorted MYH7 variant hiPSC-CMs into bins based on βMHC abundance and then deeply sequenced each bin to determine the genotypes. This enabled us to calculate variant abundance scores for 297 variants. This assay identified 12 out of 13 known pathogenic MYH7 missense variants as functionally abnormal (low abundance scores), resulting in a sensitivity of 92%. Furthermore, this assay identified 9 out of 10 known benign variants as functionally normal (normal abundance scores), resulting in a specificity of 90%. The overall accuracy of the assay was 91%, and the strength of this assay as assessed by OddsPath was moderate, which enabled the formal reclassification of 17 VUS by following the variant interpretation framework recommended by the American College of Medical Genetics and Genomics. In summary, we have developed a scalable method to generate and functionally annotate MYH7 variants in cardiomyocytes that enables accurate variant interpretation. This strategy can help reclassify VUS at scale and provide functional evidence for the interpretation of potentially all possible MYH7 variants that have yet to be encountered.