High tumor mutation burden (TMB) is an emerging selection biomarker for immune checkpoint blockade in tumors such as melanoma and non-small cell lung cancer. TMB is typically calculated from whole genome sequencing or whole exome sequencing (WES) data. Recently, clinical trials showed that TMB can also be estimated from targeted sequencing of a panel of only a few hundred genes of interest, which can be performed at a high depth for clinical applications.  In this study, we systematically investigated the distribution of TMB and preferences at the gene and mutation level, as well as the correlation between TMB calculated by WES and panel sequencing data using somatic mutation data from 15 cancer types from The Cancer Genome Atlas (TCGA).  We proposed a pan-cancer TMB panel and demonstrated that it had a higher correlation with WES than other panels. Our panel could serve as a reference data-set for TMB-oriented panel design to identify patients for immunotherapy.