Fine to ignore most substantial witness (6)
I believe the answer is:
attest
'witness' is the definition.
(I've seen this before)
'fine to ignore most substantial' is the wordplay.
'fine' becomes 'f' (abbreviation).
'to ignore' suggests deleting specific letters.
'most substantial' becomes 'fattest' (fat can mean large or substantial).
'fattest' with 'f' taken away is 'ATTEST'.
(Other definitions for attest that I've seen before include "Swear to" , "Make evident" , "Affirm by oath" , "Verify" , "Vouch for" .)