ClinVar Miner

Submissions for variant NM_004369.3(COL6A3):c.7103G>A (p.Gly2368Asp) (rs746420745)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000555679 SCV000657388 uncertain significance Bethlem myopathy 1 2017-02-27 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 2368 of the COL6A3 protein (p.Gly2368Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is present in population databases (rs746420745, ExAC 0.02%) but has not been reported in the literature in individuals with a COL6A3-related 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 COL6A3, missense variants at these glycine residues are significantly enriched in individuals with disease (PMID: 15689448, 24038877) compared to the general population (ExAC). In summary, this variant is a novel missense change affecting a residue that is critical for protein structure, stability and function. 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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