We performed an initial study on the feasibility of selecting principal isoforms using a number of prediction methods (18). The methods used to pinpoint principal functional isoforms were based on conservation and the characteristics of known proteins, principally structural and functional features. We determined a principal variant for 179 of the 215 human genes in the study, 83% of genes with multiple alternative variants. Where the principal variants selected in the study differed from the SwissProt display sequences, we found annotation evidence from cross-species alignments that supported our selection over the SwissProt display sequence.