Frameshift Mutation

Question

With regards to LMNA frameshift mutations further downstream in the tail region, specifically (p.Arg455Gln fs*5) which has yet to be found/recorded in any medical literature...Does anyone have any knowledge regarding frameshift mutations (esp. concerning LMNA)? Is it possible that this is a "background mutation" and of little consequence?

Answer 1

Check in gnomAD. It is not in the population. It truncates the protein and the protein has a pLI of 1. So it does not tolerate LoF mutations. This mutation removes the lamin tail domain.