An area very often overlooked is an accumulation of STC for modifications.
Some years ago a C337 accident in the USA which I recall was an inflight break up; wing separation ..
The aircraft was modified with Vortex generators, and no doubt with an approved AFM supplement and STC. I recall the aircraft had modified wing tips; drooping. The airframe also has a STOL kit fitted with revised aileron and drooping ailerons when flap extended. Also in the mix was a 'speed kit' a series of revised cuffs etc at various fuselage/wing areas and the booms to the tailplane.
Each and every one of the mods was applied in accordance with the various STC's
BUT: no one had certified the COMBINATION of all the mods as one package.
In effect the aircraft was destined for another life. The aircraft was no longer a C337 but a highly modified airframe that resembled at C337.