SCN5A and heart disorder: This difference may be due in part to the comparatively large fraction of reported SCN5A variants that do not perturb peak current yet are still associated with cardiac diseases compared to KCNQ1, such as LQT3 variants with increased late current but no change in peak current; BLAST-PSSM is sensitive to evolutionary fitness of residue changes which may be more homogeneously dependent on peak current for KCNQ1 and more heterogeneous for SCN5A. Alternatively, the spatial distribution of IKs peak current may be more heterogeneous than for INa.