While this variant has shown limited penetrance, the high prevalence of young cancer patients in our cohort, including 4 pediatric patients with CNS tumors, and lack of demographic, environmental or other modifiers that could account for the phenotypic heterogeneity, suggests that early and strict detection tests and surveillance should be continued for known carriers of TP53 p.Arg181Cys, akin to those recommended in classical LFS. Here, TP53 is linked to cancer.