ClinVar Miner

Submissions for variant NM_004369.3(COL6A3):c.6898G>A (p.Gly2300Arg) (rs763348222)

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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 RCV000286359 SCV000337268 uncertain significance not provided 2015-11-17 criteria provided, single submitter clinical testing
Invitae RCV000538135 SCV000657381 uncertain significance Bethlem myopathy 1 2018-10-15 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 2300 of the COL6A3 protein (p.Gly2300Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs763348222, ExAC 0.02%). This variant has not been reported in the literature in individuals with COL6A3-related disease. ClinVar contains an entry for this variant (Variation ID: 284586). 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.
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000538135 SCV000746531 likely pathogenic Bethlem myopathy 1 2017-12-03 criteria provided, single submitter clinical testing

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