ClinVar Miner

Submissions for variant NM_001849.3(COL6A2):c.1348G>C (p.Glu450Gln) (rs757846451)

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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 RCV000383351 SCV000342777 uncertain significance not provided 2016-06-07 criteria provided, single submitter clinical testing
Invitae RCV000537812 SCV000657103 uncertain significance Bethlem myopathy 1 2017-04-19 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glutamine at codon 450 of the COL6A2 protein (p.Glu450Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine. While this variant is present in population databases (rs757846451), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. 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: 288611). 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: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a rare missense change with uncertain impact on RNA splicing and 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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