vMix supports two types of Shortcuts: Local and Global.
Global shortcuts are saved in the vMix settings and will be remembered each time vMix is opened.
Local shortcuts are saved in Presets and will only be remembered if a Preset is saved and subsequently opened later.
Local shortcuts take preference over Global shortcuts, so if you have two shortcuts assigned to the letter A, one local and one global, the local shortcut will be triggered and the global shortcut will be ignored.