It could very well be the gun, Wally. In 1998 I had a brand-new 5 1/2" .45 Blackhawk with two chambers bored not only off center-but, off-axis as well. It gave 14" 100 yard groups from ammo that had proved capable of 4", in a duplicate, non-screwed-up 5 1/2" Blackhawk.
I would go all over that cylinder with a good set of micrometers before I damned multiple bullets. If it checks out OK, have your cylinder throats reamed to a uniform 0.4525" and I'll bet your groups with all your bullets will shrink and round up nicely.