ClinVar Miner

Submissions for variant NM_004369.3(COL6A3):c.8437G>A (p.Gly2813Arg) (rs146131332)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498851 SCV000590550 uncertain significance not provided 2017-06-16 criteria provided, single submitter clinical testing The G2813R variant in the COL6A3 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The G2813R variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G2813R variant is a non-conservative amino acid substitution, which occurs at a position where amino acids with similar properties to Glycine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret G2813R as a variant of uncertain significance.
Invitae RCV000653578 SCV000775459 uncertain significance Bethlem myopathy 1 2018-01-03 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 2813 of the COL6A3 protein (p.Gly2813Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs146131332, ExAC 0.01%). This variant has not been reported in the literature in individuals with COL6A3-related disease. ClinVar contains an entry for this variant (Variation ID: 432788). 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: "Tolerated"; PolyPhen-2: "Not available"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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