Although eukaryotic cells express a wide range of alternatively spliced transcripts, it is not clear whether genes tend to express a range of transcripts simultaneously across cells, or whether most genes produce dominant isoforms, either in a tissue-specific manner or regardless of tissue. To date large-scale investigations into the pattern of transcript expression across distinct tissues have produced contradictory results. Here we attempt to determine whether genes express a dominant splice variant, but at the protein level. We interrogate peptides from 8 large-scale human proteomics experiments and databases and find that there is a single dominant protein isoform, irrespective of tissue or cell type, for the vast majority of the protein-coding genes in these experiments, in partial agreement with the conclusions from the most recent large-scale RNAseq study. Remarkably the dominant isoforms from the experimental proteomics analyses coincided overwhelmingly with the reference isoforms selected by two completely orthogonal sources, the CCDS consensus variants, which are agreed upon by separate manual genome curation teams, and the principal isoforms from the APPRIS database, predicted automatically from the conservation of protein sequence, structure and function.