Strategies to shortlist True LoF mutations

Question

[kautilya]

I was curious as to what strategies are applied by everyone to shortlist true LoF(Loss of function) variations post variant annotation.

Some of the ones I could get from literature and tools are:-

1. Selecting the variations which are stop codon introducing/splice site disrupting/indels disrupting reading frame
2. Removing the variants present towards the end of transcripts
3. Removing the one where the LoF allele is same as the ancestral one
4. Removing variations in introns/exons with non-cannonical splice sites.

Also are there any other tools which can automatically filter and help find true LoF variations

Answer 1

[Jean-Karim Heriche]

The cBioPortal provides a functional impact score for mutations using mutation assessor (Reva B, Antipin Y, Sander C. Nucleic Acids Research (2011) Predicting the Functional Impact of Protein Mutations: Application to Cancer Genomics).

[kautilya]

Thanks for the answer. The tool is helpful but could not find any annotation/filtering regarding Lof however will use it add some annotations which might be helpful in filtering the Lofs