Pathogenic variants that alter protein code often disrupt splicing Approximately 10% of exonic mutations altered splicing, mostly by disrupting multiple stages of spliceosome assembly. We present a large-scale characterization of exonic splicing mutations using a new technology that facilitates variant classification and keeps pace with variant discovery. Assay of nearly 5,000 mutations reveals roots of genetic splicing errors “Splicing errors can be very deleterious because instead of just changing one amino acid [the building block of a protein], it can…