ClinVar

Description

This sequence change replaces isoleucine with valine at codon 301 of the CCDC151 protein (p.Ile301Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs750661034, ExAC 0.002%) but has not been reported in the literature in individuals with a CCDC151-related disease. The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. In addition, algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. Algorithms developed to predict the effect of nucleotide changes on mRNA splicing suggest that this variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a rare missense change that is not predicted to affect protein function or cause disease but is predicted to affect mRNA splicing. However, the evidence is insufficient at this time to prove either of these predictions conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.