We discovered novel translocations juxtaposing IGLL5 with IGH and detected high-frequency mutations in IGLL5. These IGLL5 mutations were mutually exclusive of RAS mutations and associated with disease progression, suggesting that IGLL5 may be involved in disease pathogenesis and/or serve as a biomarker of high-risk MM. The gene discussed is IGLL5; the disease is Miyoshi myopathy.