ClinVar Miner

Submissions for variant NM_001848.2(COL6A1):c.814G>C (p.Gly272Arg)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000705919 SCV000834940 pathogenic Bethlem myopathy 1 2018-07-13 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 272 of the COL6A1 protein (p.Gly272Arg). 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 to be de novo in an individual affected with developmental delay and hypotonia (Invitae). 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 COL6A1, missense variants at these glycine residues are significantly enriched in individuals with disease (PMID: 15689448, 24038877) compared to the general population (ExAC). The observation of one or more missense substitutions at this codon (p.Gly272Asp and p.Gly272Val) in affected individuals suggests that this may be a clinically significant residue (PMID: 15955946, 28182637). For these reasons, this variant has been classified as Pathogenic.

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