ClinVar Miner

Submissions for variant NM_001849.3(COL6A2):c.847G>A (p.Gly283Arg) (rs267606748)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000269898 SCV000342626 uncertain significance not provided 2016-06-06 criteria provided, single submitter clinical testing
Invitae RCV000816890 SCV000957419 pathogenic Bethlem myopathy 1 2018-11-20 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 283 of the COL6A2 protein (p.Gly283Arg). 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 observed in several individuals affected with Ullrich congenital muscular dystrophy including at least one individual in whom this variant was noted to be de novo (PMID: 24038877). ClinVar contains an entry for this variant (Variation ID: 17167). This variant disrupts the p.Gly283 amino acid residue in COL6A2. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 24038877), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. 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 COL6A2, missense variants at these glycine residues are significantly enriched in individuals with disease (PMID: 15689448, 24038877) compared to the general population (ExAC). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000018707 SCV000038990 pathogenic Ullrich congenital muscular dystrophy 1, autosomal dominant 2009-07-07 no assertion criteria provided literature only

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