Figure 2 displays the distribution of the involved MMR proteins; all LS cases identified by the 4-panel approach would also have been identified by a 2-panel approach including only PMS2- and MSH6-IHC. No germline POLE/POLD1 variants affecting function were identified. LS patients with path_MSH6 and path_PMS2 variants were older than those with path_MLH1 and path_MSH2 variants (median age = 63, 62, 50, and 50 years, respectively, P = .01; Supplementary Table 1, available online). The gene discussed is POLE; the disease is Leigh syndrome.