Whereas each individual gene had a relatively low sensitivity for PC (22–44%), combinations of ST6GALNAC3, ZNF660, CCDC181, and HAPLN3 ctDNA methylation had 100% specificity and 37–67% sensitivity; thus, by combining multiple ctDNA markers, we increased the sensitivity while retaining 100% specificity. This evidence concerns the gene ZNF660 and pachyonychia congenita.