The 2013–2014 H1N1 season matrix gene nAMPS were markedly higher than the prior and following H3N2 seasons. Since the same matrix gene assay is used for both subtypes, it was possible these differences could have reflected seasonal differences in Influenza illness severity; however, sequence analysis suggested that the differences were better explained by sequence drift in the matrix gene that had occurred by the 2012–2013 season, and was unchanged in the 2014–2015 season. Since the nAMP averages from the synthetic single stranded DNA of the H3N2 and H1N1 capture probe sequences closely matches those of the seasonal averages, sequence variation between the H3N2 and H1N1 viruses offers the best explanation for the seasonal differences.