Our study in cells supports a pathogenic role for the three new rare TMPO variants p.(Gly395Glufs*11), p.(Ala240Thr) and p.(Leu124Phe) identified in five cardiomyopathy families, in particular by altering cell proliferation and/or proper function of chromatin-associated proteins such as BAF, HMGN5 and E2F1, with expected consequences on gene structure/expression. The gene discussed is E2F1; the disease is cardiomyopathy.