MPN and lymphoma predisposed by germline DDX41 CV. (A) The occurrence of somatic DDX41 variants in MPN patients is more frequent in patients with germline CV (25%) compared with patients with VUS (9%; 1/11, P = .4) or patients not carrying germline DDX41 variants (DDX41⁻, 0%, P < .0001). (B) There appears to be a lower concomitant somatic mutation burden in patients with CV (mean ± standard error of the mean: 0.5 ± 0.5), compared with those with WT DDX41 (DDX41⁻, 2.6 ± 0.1, P = .05) and VUS (1.5 ± 0.4, P > .05). (C) No mutations in JAK2 or CALR were seen in MPN with CV, whereas these canonical variants are seen in 73% (8 of 11) of MPN patients with VUS and 82% in the WT cohort (P < .0001). (D-E) Circos plot diagrams illustrate the pairwise co-occurrence of variants and cytogenetic events in MPN patients with germline CV (D) and VUS (E). Genetic variants and cytogenetic events listed in Figure 2 appear in descending order clockwise starting at 12 o’clock. Each link (ribbon) indicates the pairwise co-occurrence of mutational events, and the width of the ribbons indicates the frequency of the co-occurrent events. TF (orange), transcription factors; nl CG (green), normal cytogenetics; s (yellow), somatic DDX41; E (light green), epigenetic modulators; SF (purple), RNA splicing factors; C (pink), CALR. (F) HM predisposed by germline DDX41 CV. AML (55%) and MDS (24%) are the most common entities predisposed by DDX41 CV, followed by cytopenia (16%), MPN (3%), and lymphoma (3%). ****P < .0001.