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Missense variants were further annotated using the REVEL score (0-1 range), which is a tool that considers in aggregate a combination of 13 individual in silico prediction tools (SIFT, PolyPhen2-HDIV, PolyPhen2-HVAR, LRT, MutationTaster, MutationAssessor, FATHMM, PROVEAN, MetSVM, MetLR, CADD, FATHMM-MKL, and fitCons) to suggest pathogenic or benign impact

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