ClinVar

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly626 amino acid residue in COL1A1. Other variant(s) that disrupt this residue have been observed in individuals with COL1A1-related conditions (PMID: 22589248, 27509835, 34529350), which suggests that this may be a clinically significant amino acid residue. This variant disrupts the triple helix domain of COL1A1. Glycine residues within the Gly-Xaa-Yaa repeats of the triple helix domain are required for the structure and stability of fibrillar collagens (PMID: 7695699, 8218237, 19344236). In COL1A1, variants affecting these glycine residues are significantly enriched in individuals with disease (PMID: 9016532, 17078022) compared to the general population (ExAC). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C55"). This variant is also known as p.Gly448Ser. This missense change has been observed in individual(s) with osteogenesis imperfecta (PMID: 22589248, 27509835, 34906519). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 626 of the COL1A1 protein (p.Gly626Ser).