ClinVar Miner

Submissions for variant NM_004369.3(COL6A3):c.8308G>A (p.Val2770Met) (rs886044644)

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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 RCV000726602 SCV000345769 uncertain significance not provided 2017-05-25 criteria provided, single submitter clinical testing
GeneDx RCV000726602 SCV000536450 uncertain significance not provided 2017-01-19 criteria provided, single submitter clinical testing The V2770M variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V2770M variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved in mammals, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Invitae RCV000548137 SCV000657425 uncertain significance Bethlem myopathy 1 2018-01-28 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 2770 of the COL6A3 protein (p.Val2770Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a COL6A3-related disease. ClinVar contains an entry for this variant (Variation ID: 291079). 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"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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