In Reply Maruvka et al analyzed the associations of MUC16 mutation with tumor mutation load (TML) and survival outcome in the Cancer Genome Atlas gastric cohort by using the Curveball algorithm1 to randomize the mutation matrix without altering the row and column totals. In our view, their analysis underestimated the variability of genetic mutation in the cohort. Their interpretations of the conclusions of our study2 may have resulted from some misunderstanding.