In summary, at least one feature of defective polymerase proofreading, i.e. presence of hypermutation, POLE/POLD1 variant-associated mutational signature SBS10 or SBS20, multinucleated cells/enlarged nuclei, and increased infiltrate of T lymphocytes and/or macrophages, was detected in 13/15 (87%) gliomas from POLE/POLD1 variant carriers compared to controls with WT POLE by multimodal assessment (Additional file 1: Table S3), with an impact on the classification of the majority of POLE/POLD1 variants identified here (Additional file 1: Table S4). Here, POLD1 is linked to glioma.