p.Arg175His, p.Arg248Trp, and p.Arg273His are three of the eight hotspot mutations (germline and somatic) reported in TP53 that have been shown to have an increased likelihood of presentation with a classic Li–Fraumeni syndrome (LFS) phenotype, earlier age of first breast cancer onset, and shorter time to diagnosis of any cancer [39]. This evidence concerns the gene TP53 and Li-Fraumeni syndrome.