ClinVar Miner

Submissions for variant NM_001849.3(COL6A2):c.2810G>A (p.Arg937Gln) (rs777354703)

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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 RCV000725046 SCV000333498 uncertain significance not provided 2015-07-31 criteria provided, single submitter clinical testing
GeneDx RCV000725046 SCV000590270 uncertain significance not provided 2017-06-06 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the COL6A2 gene. The R937Q variant has been reported previously in an individual with Bethlem myopathy who had two other COL6A2 variants identified; however, parental testing was not completed (Stehikova et al., 2016). The R937Q 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 R937Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000542705 SCV000657178 uncertain significance Bethlem myopathy 1 2017-06-23 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 937 of the COL6A2 protein (p.Arg937Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs777354703, ExAC 0.01%). This variant has not been reported in the literature in individuals with a COL6A2-related disease. ClinVar contains an entry for this variant (Variation ID: 282183). 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 C0"). In summary, this variant has uncertain impact on COL6A2 function. 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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