Support search for change in 2 nucleotides in codon resulting in AA change

[dsonkin]

Hello

Support search for change in 2 nucleotides in codon resulting in AA change. For example, NP_004324.2:p.Val600Lys, requires change in 2 nucleotides (NM_004333.6:c.1798_1799delinsAA). Variants requiring change in 2 nucleotides are not very frequent, however like BRAF V600K some of them are rather clinically important.

Thank you
Dmitriy

[jfjlaros]

I am not sure this would be a useful extension because the number of ways to change one amino acid to an other using two substitutions can become rather large.

For example, there are 18 ways to convert Arg to Pro with two substitutions.

[dsonkin]

Perhaps changes to search for could be limited to AA, CC, GG, TT, which are most frequent types of dinucleotide changes.

[jfjlaros]

I would not be in favour of that, I prefer to cover either none or all of the cases.

I will leave this feature request open for now, but since Mutalyzer 2 is no longer maintained and this library is not part of Mutalyzer 3 yet, I do not expect to work on this any time soon.

@mihailefter: any comments on the Mutalyzer 3 integration?

Notes

• The result of the backtranslation is a dictionary, containing sets of substitutions indexed by the position within the codon. Every substitution represents one solution, every combination of one element is trivially valid.
• This model cannot be used for multiple substitutions, as some combinations of two elements are valid, but others may not be.
• Mutalyzer 2 breaks when this model is changed.
• This model will be reconsidered when support in Mutalyzer 3 is on the agenda.