APPRIS is the first database to include principal isoforms on a genome-wide scale. Previously all database and large-scale studies have had to resort to selecting the largest annotated isoform as the reference variant. We have shown that this conservative solution is not ideal (18). The lack of reliably identified principal isoforms in annotation databases is an omission that is only going to become more glaring with time as the numbers of annotated variants in the sequence databases grow.