Add application specific shortcuts. Doing this outside of mumble is very hard. (Using a custom layout doesn't change anything for instance)
Users have application specific needs for their shortcuts:
For example In games it's important that the push-to-talk key is close and easily usable, keys like these can be found that don't have other uses in gaming.
At the same time, the same key outside of gaming most probably has uses, and every time it's pressed the channel is opened thus annoying other users in mumble. The user might not need a hotkey so close out of gaming and could pick a key farther away, that isn't used as much.
Outside of remapping the keys every time the user starts and stops using an application with specific needs for mumble, the only other way to do this is with application specific shortcuts.