I have a single six. I fired lead .22 LR ammo in it, then switched to the .22 mag cylinder. I was keyholing every 3rd or 4th bullet at a distance of 10 yds. I took it home and gave it a good cleaning to clean out the metal fouling. When I went back to try it again, the magnums shot just fine.
Get rid of the fouling in the forcing cone area.