How to obtain genomic coordinates of point mutations given in protein/amino acid notation

Question

[Friederike]

Hi,

I have a list of mutations using the protein sequence as a reference, e.g. JAK1 G1097D. I would like to obtain the genome coordinates of the actual base pairs encoding the affected codon. Ideally, all I have to do is supply the gene identifier (including the organism) and the mutation and in return I get the genome coordinates.

I can think up a couple of ways to address this problem, but I'm sure there must be a solution out there already -- my web searching has failed me so far, so please do share your bookmarks!

Thanks!

Answer 1

[Emily]

You can put them into the Ensembl VEP. You can use HGVS as your input and it will give you genome coordinates (amongst other things), in the output.

[Friederike]

thanks for the hint! I seem to struggle with the input though, e.g. none of these have produced any results for the above mentioned mutation of JAK1. I've tried all combinations of ENST* or ENSG* identifiers, the notation of the mutation with 1097Gly>Asp, which seemed to me the one in the examples, as well as Gly1097Asp, which seemed to be the one outlined at the SVN page. Using the single-letter notations for the amino acids also didn't work.

• ENST00000342505:p.1097Gly>Asp
• ENSG00000162434:p.Gly1097Asp

I've tried this via the website using the default settings. Any additional hints?

[Emily]

HGVS notation for protein is :p.3-letter_amino_acid+position+3-letter_amino_acid, ie :p.Gly1097Asp. To use this you need a protein ID (eg NP or ENSP) or a protein name.

The following work:

JAK1:p.Gly1097Asp

ENSP00000343204:p.Gly1097Asp

If you use a gene ID it doesn't work at all, if you're using a transcript ID it expects CDS coordinates.

[Friederike]

of course, using an actual protein ID makes sense! :) thanks for pointing that out!

Answer 2

[Friederike]

Just for future searches: I finally found this old Biostars post that addressed exactly my problem. The solution that worked best for me was to use TransVar -- it also helped me figure out which input format it needed by returning a somewhat sensible error message as long as it didn't find anything.