Data Of Sift And Polyphen

Question

[abinaya.elavarasan]

i would like to know on what cases of data does polyphen2 and sift will not work(e.g they don't work for synonymous changes) .. i would like to know the other cases ?? and i would also like to know some other tools which would work for the exception case??

thanks in advance

Answer 1

[Alex Paciorkowski]

Just take a look at the PolyPhen-2 and SIFT webpages, the information is there:

PolyPhen-2

PolyPhen-2 (Polymorphism Phenotyping v2) is a tool which predicts possible impact of an amino acid substitution on the structure and function of a human protein using straightforward physical and comparative considerations.

SIFT

SIFT predicts whether an amino acid substitution affects protein function. SIFT prediction is based on the degree of conservation of amino acid residues in sequence alignments derived from closely related sequences, collected through PSI-BLAST. SIFT can be applied to naturally occurring nonsynonymous polymorphisms or laboratory-induced missense mutations.

So, both are used to predict the effect on a protein of an amino acid substitution -- those are caused by nonsynonymous variants. That's what these prediction tools were designed to do. They don't help you with other types of genetic changes.

Do you mean by "exception case" other variation that can happen in the human genome? (Because those other variations are not rare, and as such can't really be considered exceptions.) Things like chromosomal translocations, copy number variants, short tandem repeats, variation in non-coding regulatory regions?

[abinaya.elavarasan]

yes sir! i would like to know what kind of variations they dont capture ?