ClinVar

Description

The COL1A1 c.1382G>C; p.Gly461Ala variant, to our knowledge, is not described in the medical literature or in gene-specific databases. It is also absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant disrupts the repeating Gly-X-Y sequence motif of the collagen triple helix and is predicted to impair collagen function (Ben Amor 2011). Additionally, another variant at this codon (c.1381G>A; p.Gly461Ser) as well as several other surrounding glycine substitutions in this exon have been reported in individuals affected with osteogenesis imperfect type II and are considered pathogenic (Marini 2007). Based on available information, the p.Gly461Ala variant is considered likely pathogenic. REFERENCES Ben Amor I et al. Genotype-phenotype correlations in autosomal dominant osteogenesis imperfecta. J Osteoporos. 2011; 2011:540178. Marini J et al. Consortium for osteogenesis imperfecta mutations in the helical domain of type I collagen: regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans. Hum Mutat. 2007 Mar;28(3):209-21.