Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000705317 | SCV000834308 | pathogenic | Osteogenesis imperfecta type I | 2018-02-14 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 854 of the COL1A1 protein (p.Gly854Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with osteogenesis imperfecta (OI) (PMID: 21520333, Invitae). For these reasons, this variant has been classified as Pathogenic. This missense change is located within a functionally conserved triple helix domain of the COL1A1 protein and variants that affect the glycine residue in Gly-Xaa-Yaa repeats of the collagen triple helix are known to disrupt protein folding and stability (PMID: 8218237, 7695699). Other missense substitutions at this codon (p.Gly854Cys and p.Gly854Ser) have been reported in individuals affected with OI (PMID: 27509835, 17078022). |