Functional Consequence of In-frame Indel

Question

[Katie D'Aco]

Does anybody include in-frame indels in association studies? A quick pubmed / google / biostars search on this didn't come up with much. In-frame indels are often treated as synonymous, but since they change the amino acid sequence, wouldn't they be more like missense variants? Are there ways of predicting which in-frame indels are more deleterious than others (besides length of indel)?

Answer 1

[Ashutosh Pandey]

PROVEAN predicts the impact of small indels on protein function.

A section from the paper relevant to your post:

In addition to single amino acid substitutions, there are other variation classes associated with disease phenotypes. For example, a common disease variant associated with the genetic disease cystic fibrosis is a deletion of phenylalanine at position 508, part of the ATP-binding domain of the CFTR protein. The prevalence of the ΔF508 allele in cystic fibrosis patients was 71% [14], [15]. In the Human Gene Mutation Database (Professional ver2011.3), at the gene sequence level approximately half of the human disease variations are associated with single nucleotide substitutions (57%), and close to one-fourth of disease mutations (22%) are associated with small indels [16], [17].