It's not so much what we can fire.
It's more of a regulation of what we can manufacture.
I'm not exactly sure how recent this regulation is, whether or not it's original National Firearms Act or if it was added language.
Technically we *can* build something with a caliber bigger than 500 but we first need to jump through a taxation and licensure hoop and pay $500 per specimen - as long as it's not a replica of an antique or obsolete system.
Antique / obsolete are typically good to go without special taxation or licensure.

For instance, a Howdah on a Jones underlever system, in 20 bore Paradox-type would likely be a straight go. Smooth bore would end up being a short barreled shotgun, and would need it's own special blessings from the crown - unless it's pinfire system, then it's ok...