Perhaps the most important implication of this study is that quantitative population averages (whether done by nAMPs as in the GenMark assay, or by Ct as would be the case in other manufacturers’ assays) appear to be sensitive to Influenza sequence changes due to seasonal drift that result in assay mismatches. In addition, it is possible that plotting the nAMPs of the matrix gene vs the subtype gene may offer a simple method to detect subpopulations with sequence variations affecting the performance of the assay. Although it does not appear that any Influenza strains were actually “missed” in our study because of mismatches between the matrix gene assay and the matrix gene sequence in circulating strains, further sequence drift in circulating strains could render the assay falsely negativee at some point.