Two examples (of many) serve to illustrate the utility of APPRIS in the selection of principal isoforms. In the first example (gene DNAJC5G), APPRIS disagrees with the CCDS annotation by selecting an isoform that is 16 residues shorter than the pair of protein sequence identical isoforms chosen as the single CCDS variant, as the Ensembl reference sequence and as the SwissProt display sequence (Figure 2A). The variant selected by APPRIS (DNAJC5G-004) has a better score in Matador3D (it maps better to the known 3D structures in the PDB) and has a conserved Pfam domain. In contrast, the longer sequences would have broken Pfam domains and 3D structure (Figure 2B). The extra exon in the CCDS variant generates a 16-residue insertion that would be likely to disrupt a 3D structure (Figure 2C) and a conserved Pfam domain (Figure 2D).
