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jodyphelan / tbdb

Standard database for the TBProfiler tool
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embB p.Pro371Arg - mutation from literature source? #64

Closed CaitlinSelway closed 1 month ago

CaitlinSelway commented 2 months ago

Hi Jody,

I'm looking to find the literature source of the mutation embB p.Pro371Arg as this has flagged as R in the resistance report, but is has the WHO grading of uncertain significance. I've had a search and cannot find this mutation in the literature. If this mutation is from the literature, could you point me to it so that I can share it with our clinicians. Otherwise, perhaps this mutation should be removed if is not from the literature. Please see the tb-profiler output at the end of the request.

Kind regards, Caitlin

Gene: embB Mutation: Pro371Arg Literature Evidence: Unknown Software version,6.2.0 Database version,82777ea

Resistance report
-----------------
Drug,Genotypic Resistance,Mechanisms
Rifampicin,,
Isoniazid,,
Ethambutol,R,embB p.Pro371Arg (1.00)
Pyrazinamide,,
Moxifloxacin,,
Levofloxacin,,
Bedaquiline,,
Delamanid,,
Pretomanid,,
Linezolid,,
Streptomycin,,
Amikacin,,
Kanamycin,,
Capreomycin,,
Clofazimine,,
Ethionamide,,
Para-aminosalicylic_acid,,
Cycloserine,,

Resistance variants report
-----------------
Genome Position,Locus Tag,Gene Name,Variant Type,Change,Estimated Fraction,Drug,Confidence,Comment
4247625,Rv3795,embB,missense_variant,p.Pro371Arg,1.000,ethambutol,Uncertain significance,Mutation from literature
jodyphelan commented 2 months ago

Hi @CaitlinSelway,

This mutation was included in the database in the original publication (https://pubmed.ncbi.nlm.nih.gov/26019726/). This mutation potentially was sourced like TBDReaMDB database. This website is now defunct so we won't be able to verify. Checking with the WHO catalogue I can see it is found in two samples that are sensitive to EMB and no resistant isolates so I would agree that we should probably remove this particular mutation.

@conmeehan @pmenzel @pvanheus any thoughts?

CaitlinSelway commented 2 months ago

Thank you for looking into this mutation @jodyphelan!

pvanheus commented 2 months ago

Agree @jodyphelan - and perhaps note in the commit why the change was made?

pmenzel commented 2 months ago

On another note, it would be nice if each mutation in TBDB could have a source attribution. I know that this would obviously a lot of work..

jodyphelan commented 2 months ago

@pvanheus yes good idea. Will get that done now.

@pmenzel yes this has been on my todo list for a while! I'll try to slowly add this info