We assign a score to every possible non-silent mutation according to its expected impact on the protein function: higher score for mutations with stronger impact.
Conversely, MEN4 adenomas usually harbor CDKN1B missense mutations, with no impact on p27Kip1 C-Terminus [ 4].
Three patients in the monotherapy arm without virological suppression acquired new resistance mutations with modest impact on LPV susceptibility.
At UniProtKB, we focus our curation efforts on gathering information from peer-reviewed literature that deals with disease-associated mutations with an impact on protein function.
These features indicate that canonical OGs are characterized by copy number amplifications or recurrent missense mutations with high impact on protein function.
The genotype in the other published variant cases was also characterized by mutations with heavy impact on the enzyme at the structural level [ 11, 23].
Most of the mutations in our discovery did not show gene level expression difference between mutated samples and wild type samples, suggesting that pathway level gene expression change is beneficial to discover mutations with functional impact.
We have proposed combining multiple mutation extraction tools together by merging their results, and have shown that their combination results in substantially improved recall of mutations with minimal impact on precision, providing evidence of the complementary nature of the tools.
Consequently, we suggest that MIC determination should be performed for all strains with a Leu533Pro genotype or for strains with mutations with unknown impact on the rifampicin MIC level.
In addition, a frequent conceptual misunderstanding relates to the fact that even a mutation with profound impact on protein function does not automatically proves its pathogenicity and disease-causing effect.
