Characterization of identified variants in blood of the RS and LLS elderly subsample. (A) Mutations in genes previously linked to hematopoietic malignancies. Barplot of the number of individuals carrying a mutation, split by genes and study. Note that only 11 of the 15 investigated genes had a mutation (see supplemental Appendix 4 for a complete list). (B) Prevalence of carriers of somatic mutations stratified by age category using data of Xie et al²  and the observations in the RS and LLS elderly subsample. (C) Distribution of VAFs of the identified mutations. (D) Comutation plot of carriers with 2 independent mutations. (E) Overview of mutations in DNMT3A identified in the RS and LLS elderly subsample. Variants are annotated at the top with color coding to indicate the impact and a shape to indicate the types of follow-up experiments. Circles indicate mutations detected in our sequencing data; squares indicate mutations also validated by Sanger sequencing; diamonds indicate mutations also validated by Sanger sequencing and absent in an IBD2 matched sib, that is, confirming somatic variations. Mutations identified in multiple carriers are indicated with stacked annotations and those having bold borders were identified in the LLS. Missense variants are only included whenever they are present on a curated list of recurrently reported variants in the Catalogue Of Somatic Mutations In Cancer (COSMIC)⁷  assembled by Jaiswal et al⁴ . Domains: ADD, histone-binding domains; DNMT, DNA methyltransferase interaction domain; MTase, methyltransferase domain; PWWP, conserved DNA binding domain; ZC-FING, zinc finger domains. COSMIC, densities of somatic variants identified in hematopoietic or lymphoid tissue collected by the Catalogue Of Somatic Mutations In Cancer (COSMIC)⁷  database: all small variants (red), missense single nucelotide variants (SNVs) (gray), small variants confirmed to be of somatic origin (blue).