Enzyme $\mathrm{X}$ catalyzes hydrolysis of GTP into GDP. The GTP-bound form of $\mathrm{X}$ transmits a signal that leads to cell proliferation. The GDP-bound form does not transmit any such signal. Mutations in $\mathrm{X}$ are found in many cancers. Which of the following alterations of $\mathrm{X}$ are most likely to contribute to cancer?