ClinVar Miner

Submissions for variant NM_004369.3(COL6A3):c.6899G>A (p.Gly2300Glu) (rs145572916)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000312497 SCV000345100 uncertain significance not provided 2016-08-18 criteria provided, single submitter clinical testing
Invitae RCV000815393 SCV000955843 uncertain significance Bethlem myopathy 1 2018-11-30 criteria provided, single submitter clinical testing This sequence change replaces glycine with glutamic acid at codon 2300 of the COL6A3 protein (p.Gly2300Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is present in population databases (rs145572916, ExAC 0.009%). This variant has not been reported in the literature in individuals with COL6A3-related disease. ClinVar contains an entry for this variant (Variation ID: 290529). 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 COL6A3, missense variants at these glycine residues are significantly enriched in individuals with disease (PMID: 15689448, 24038877) compared to the general population (ExAC). However, although this variant involves a glycine residue in the triple helix domain of COL6A3, it does not form the consensus Gly-Xaa-Yaa repeat. In summary, this variant is a rare missense change affecting a residue in the triple helix domain. However, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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