ClinVar Miner

Submissions for variant NM_001849.3(COL6A2):c.2002G>A (p.Glu668Lys) (rs138948335)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000512668 SCV000196785 uncertain significance not provided 2016-03-04 criteria provided, single submitter clinical testing The E668K variant has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The E668K variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The E668K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret E668K as a variant of uncertain significance.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000512668 SCV000342644 uncertain significance not provided 2016-06-06 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000512668 SCV000609064 uncertain significance not provided 2017-02-01 criteria provided, single submitter clinical testing
Invitae RCV000808953 SCV000949087 uncertain significance Bethlem myopathy 1 2018-08-16 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 668 of the COL6A2 protein (p.Glu668Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs138948335, ExAC 0.02%). This variant has not been reported in the literature in individuals with COL6A2-related disease. ClinVar contains an entry for this variant (Variation ID: 162537). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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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