Right now it is wearing an old Weaver steel-tube, straight-pipe K2.5 fixed. Sometimes I pop it off and drop on a NECG peep sight that is also zeroed for that rifle, depending on the mood I'm in and what I am shooting at. It also has a stock that was shortened about 1", which turned out just right for that little gun.
Admittedly, it is a little harder to manipulate the smallish rounds, as compared to full-size rifle rounds. The scope isn't really the problem. The cartridge has to be pushed into the saddle in the receiver, over the falling block, and into the chamber. With pointy rifle cartridges that are longer than the saddle and block, it is just putting a round peg in a round hole. No problem. With the shorter .357, my fat thumb gets in the way. I also shoot wide-nosed bullets that can sometimes hang up while chambering them. This only becomes an issue if I am trying to load a second round quickly. I usually don't have to reload quickly, because the jackrabbit is either already dead, or running 40mph away from me through the sagebrush, (at which point I just smile, and go find another, less lucky one). You can also adjust the extractor to just extract the empty case, or eject it completely, depending on your needs.
I tested all sorts of ammo through it when I first bought it, both factory and handloads. The heavier the bullet, the better it shot. Factory 158s were all about 1.5-2 inches at 100 yards, off the bench with better optics than what it has now. I believe the Federal brand did the best. Not too impressive, but adequate for hunting at limited distances. The 180 grain XTPs and SSPs shoot right at an inch, and that's all I shoot through it now. Your rifle may have entirely different preferences.
Something to keep in mind: Most revolver bullets are designed to perform at impact velocities expected from a revolver. Driving them through a 22" barrel increases the velocity substantially, and that changes the impact dynamics of the bullet. A 110 or 125 grain revolver bullet at rifle velocities acts more like a grenade than a bullet. Penetration will be less at higher velocities because the expansion (fragmentation) will be greater and sooner after entry. A broadside lung shot between the ribs would be fine, but don't expect it to always penetrate to the vitals through a shoulder or a rear quarter. This is where I rely on mass, not velocity, to carry it through, and a tough enough bullet to retain that mass long enough to reach the vitals. I realize we are now entering a hotly debated topic, but this is merely my opinion based on my observations.
Despite its inherent limitations, it is still one of my favorite little rifles. I just choose to operate within its limitations and not try to make it into something it is not.
Regards,
Schuter