rs761278503

Description

Curator: Arleen D. Auerbach. Submitter to LOVD: Yukihide Momozawa.

This sequence change replaces serine with cysteine at codon 1089 of the BRIP1 protein (p.Ser1089Cys). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and cysteine. This variant is not present in population databases and has not been published in the literature. 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. In summary, this is a novel missense change that is not predicted to affect protein function or cause disease. However the evidence is insufficient at this time to prove that conclusively. It has been classified as a Variant of Uncertain Significance.

The p.S1089C variant (also known as c.3266C>G), located in coding exon 19 of the BRIP1 gene, results from a C to G substitution at nucleotide position 3266. The serine at codon 1089 is replaced by cysteine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.