MRC1 and neoplasm: Thus, typically diagnostic pathways for LS testing in EC comprise three sequential steps: (i) functional MMR tumour testing (via IHC or MSI), followed by (ii) somatic MLH1 promoter hypermethylation analysis of tumours exhibiting MLH1 protein loss on IHC or MSI and then (iii) germline genetic sequencing of MMR genes to identify PVs (figure 1).