MDS and AML occur in individuals with a heterozygous germline frameshift variant or a missense variant within the DEAD-box domain of DDX41 by later acquiring a somatic variant in the other allele, typically p.R525H (or p.G530D, etc., in a few cases) within the helicase domain [61,63,64] (Figure 1A). Here, DDX41 is linked to acute myeloid leukemia.