421 is a No Go, many switchbacks over mountains, did it one time, never again.
321 is doable but very slow around Watauga Lake, and around construction at Blowing Rock.
Can head west toward Marion, 221 from around Marion to Linville, then 194 to 19E to TN, then I81 is best if don't like interstates.
If interstates okay, then go south from Lenoir to I40 to Asheville, then I26 to I81, farther route, but quickest also, and no problem with mountains.
2012 Itasca Cambria 28T