In this paper, three commercial whole-exome sequencing platforms — from Agilent, Nimblegen and Illumina — are systematically compared based on their ability to detect variants in the same human sample. The balance between exome coverage and target-enrichment efficiency was influenced by the different design features (such as bait density) and parameter settings of each platform. Interestingly, exome sequencing detects variants that are missed by whole-genome sequencing, suggesting that deep-targeted sequencing affords greater sensitivity than even genome coverage.