SF3B1is the most prevalent splicing factor mutated in myeloid neoplasms, detected in 20-30% of patients with myelodysplasia (MDS) and associated with a milder disease phenotype. SF3B1mutations are typically single nucleotide variations occurring in hotspots in the HEAT domain. Disease-specific SF3B1hotspot predilection is observed; for example, K700E is most common in MDS and R625 in uveal melanoma. The K666 hotspot has been associated with increased risk of MDS disease progression to acute myeloid leukemia (AML). However, the prognostic impact across all myeloid neoplasms inclusive of myeloproliferative neoplasms (MPN) and MDS/MPN overlap syndromes has not been established.