Only one of the 11 MSH6 variations (p.E1193K) reliably indicates pathogenicity with the three-step approach of assessment (Table 3) as seen by the lack of MSH6 by IHC (STEP1), by in vitro MMR deficiency (STEP2, in silico results not available), and by reduced MSH2 interaction capability (STEP3). The gene discussed is MSH6; the disease is mismatch repair cancer syndrome 1.