ClinVar Miner

Submissions for variant NM_001849.3(COL6A2):c.2326G>A (p.Ala776Thr) (rs759293889)

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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 RCV000367936 SCV000340066 uncertain significance not provided 2017-11-14 criteria provided, single submitter clinical testing
Invitae RCV000557776 SCV000657142 uncertain significance Bethlem myopathy 1 2016-06-25 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 776 of the COL6A2 protein (p.Ala776Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs759293889, ExAC 0.07%) but has not been reported in the literature in individuals with a COL6A2-related disease. This variant occurs outside of the conserved triple-helical domain of the type 6 alpha-2 collagen protein where amino acid substitutions are rarely pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. It is not expected to cause 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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