Illustrative case of deleterious DDX41 variants identified during clinical evaluation of a hematopoietic malignancy. (A) Family history revealed 2 cancers in the patient/proband (red circle), a blood cancer of unclear nature in the father, and a head and neck cancer in the paternal grandmother. (B) Molecular profiling via a 150-gene clinical NGS panel identified 171 total variants. After annotation, filtering for clinical relevance, and individual verification by the in-house pathologist, 7 (4%) were reported as variant of uncertain significance, and the 2 (1.1%) DDX41 variants were reported as pathogenic on a final document provided to the treatment team. (C) DDX41 allele VAF is graphed throughout the patient’s clinical course for the 2 variants identified. AML, acute myeloid leukemia.