Five variants, R37W, T453M, T603M, L607F and S704C, are predicted to be deleterious by all three applied prediction algorithms (PolyPhen-2, Pmut and Panther; Supplementary Table S2). From this set, the functional effects of the common variants L607F (rs6675281) and S704C (rs821616) have been well documented in the literature, as mentioned earlier. R37W lies within a defined nuclear localisation signal71 and PDE4B binding site72 and is seen in a single case of rMDD (discussed at the end of this section). T453M is present at low frequency in cases and control individuals, both in this study and others (Supplementary Table S3). T603M was only identified in a single control, but Song et al.11 reported a T603I variant in a schizophrenic individual that was absent in their set of control individuals (Supplementary Table S3).
