Since HEK293 cells co-expressing IDH1-R132H-V5 with F-CIC or F-CIC-R201W produce less 2HG compared to the cells co-expressing IDH1-R132H-V5 and F-CIC-R1515H, it is tempting to speculate that in gliomas, missense mutations in the HMG domain alter its function to produce a 2HG level for tumour cells that balances cell survival and increased tumorogenicity, and for this reason such mutations are observed more frequently than missense mutations in the protein binding domains. The gene discussed is IDH1; the disease is central nervous system cancer.