17  DDX41

• DDX41 is located at 5q35.3, and its mutation has unique features of male predominance and long-term cytopenia before the development of myeloid neoplasms.

• DDX41 is important in gene splicing and in the innate immune system/STING pathway

• 2-6% “sporadic” adults MDS/AML worldwide

• MC somatic variant will be R525H

• Two DDX41 variants in myeloid HM is highly suggestive of an underlying germline DDX41 variant

• Possible solid tumors?

• Possible Auto-immunity?

• Germline deletions exist for DDX41 and are often missed by “somatic” tumor profiling panels so be careful about what testing platform is used for germline testing.