It definitely doesn’t require a reboot. My best guess at this point is that putting the system to sleep, or possibly even just changing configurations (i.e. undocking the laptop, moving from single- to dual-monitor configurations) will do it. Either way, I was never seeing this previously. I don’t know precisely when this started happening, so it’s also possible that it coincided with a graphics driver update, an update to the Creators Edition of Windows 10 — hard to say.
Is it possible to suspend automatic saving of snapshots. In other words, can I get the setups I want, save them, then disable any changes until I re-enable that? Or, maybe I should ask this question — other than when I specifically update a layout, when does Mosaico try to save the current layouts? That might help determine the source of the corruption.