Splicing impact of deep exonic missense variants in CAPN3 explored systematically by minigene functional assay

Improving the accuracy of variant interpretation during diagnostic sequencing is a major goal for genomic medicine. To explore an often-overlooked splicing effect of missense variants, we developed the functional assay ("minigene") for the majority of exons of CAPN3, the gene responsible for limb girdle muscular dystrophy. By systematically screening 21 missense variants distributed along the gene, we found that eight clinically relevant...