ClinVar Miner

Submissions for variant NM_004369.3(COL6A3):c.6193G>C (p.Gly2065Arg) (rs397515332)

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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 RCV000329760 SCV000337555 likely pathogenic not provided 2015-12-11 criteria provided, single submitter clinical testing
Invitae RCV000653528 SCV000775409 pathogenic Bethlem myopathy 1 2018-01-10 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 2065 of the COL6A3 protein (p.Gly2065Arg). 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 not been reported in the literature in individuals with COL6A3-related disease. ClinVar contains an entry for this variant (Variation ID: 284796). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). A different missense substitution at this codon (p.Gly2065Asp) has been determined to be pathogenic (PMID: 18825676, 27447704). Glycine residues within the triple helix region are crucial to maintain fibrillar collagens structure and stability (PMID: 7695699, 19344236). In the case of COL6A3, missense substitutions that affect glycine residues within the triplex helix domain have been reported in many patients affected with collagen VI myopathy (PMID: 24038877). For these reasons, this variant has been classified as Pathogenic.

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