Defining LoF mutations with Annovar

Question

[QVINTVS_FABIVS_MAXIMVS]

I have annovar gene and exon annotations for SNVs and I would like to get the Loss of Function (LoF) alleles from this list.

Using the annovar annotations are these considered to be LoF?

• frameshift (insertion/deletion)
• stopgain
• stoploss
• splicing (?)

Any input is appreciated :)

Answer 1

[mforde84]

You'd have to look at the protein to really be sure. The first three are probable, especially if they are early on in the coding sequence (e.g., exon 1 / 2). Splicing might be LOF, GOF, both, benign. For example, say a silenced oncodriver is spliced into an actively transcribed oncosuppressor and in such a way that disrupts the suppressor.