Potential somatic hypermutation motifs are restricted to the FR1 and CDR1 for IgM and IgW VH genes. The FR and CDR nucleotide sequences for all IgM and IgW cDNA clones were analyzed for the Ser codon potential somatic hypermutation motif AGC/T (AGY red square) and the non-hypermutated Ser codon nucleotide sequence TCC/T/A/G (TCN yellow square). IgM significantly uses the AGY sequence in the FR1 and CDR1 (p < 0.01, one-way factorial analysis of variance (ANOVA), n = 23) while IgW uses this motif in the CDR1 (p < 0.01, ANOVA, n = 16). The non-hypermutated motif was significantly enriched in the FR3 region for both Ig VH families (p < 0.01, ANOVA) and neither motif was present in all FR2 analyzed.