Mutations in TP53 and RB1 have been shown to participate in the development of malignant brain tumors. Emerging evidence shows that mutations are involved in LGI1 in brain tumor progression. Herein we present data from the sequencing of a series of high- and low-grade gliomas with matched normal DNA. We report on 35 unique missense mutations in TP53, RB1 and LGI1 genes and use available information for each mutation in order to classify them as likely to be ‘driver’ or ‘passenger’ mutations. The identification of putatively deleterious mutations in LGI1 supports the notion that this locus may play a role in brain cancer development.