E592K induces unique RNA missplicing events. TF1 cells transduced with different SF3B1 variants were analyzed by RNA-seq, with (A) highest-scoring ΔPSIs shown. (B) Western blot with anti-SF3B1 antibody. (C) End point PCR/quantitative PCR validation of K700E–specific missplicing events. (D) Validation of E592K-specific events. (E) RNA-seq reads from TF1 cells showing the cryptic event in EZH2. (F) Orthogonal validation of missplicing in heterozygous SF3B1 knockin hiPSCs. PTC, premature termination codon.