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Yes. While this applies to most applications, it's not consistent between games. Ubisoft games, for instance, are notorious for their menu systems failing notice a system-set button reversal. In those cases I can set the R-button for primary fire / select and the L-button for secondary (Hacker-vision in Watch Dogs 2, for instance, since I aim / use iron-sights with Numpad-5) but any in-game menus still require an unreversible left-click, which I have to either deal with or work around.