ClinVar Miner

Submissions for variant NM_001848.2(COL6A1):c.631C>T (p.Arg211Cys) (rs375217284)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493688 SCV000582458 uncertain significance not provided 2018-11-23 criteria provided, single submitter clinical testing The R211C variant in the COL6A1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R211C variant is observed in 16/73,228 (0.022%) alleles from individuals of non-Finnish European background in large population cohorts (Lek et al., 2016). The R211C 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. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret R211C as a variant of uncertain significance.
Invitae RCV000695796 SCV000824317 uncertain significance Bethlem myopathy 1 2018-08-06 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 211 of the COL6A1 protein (p.Arg211Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs375217284, ExAC 0.05%). This variant has not been reported in the literature in individuals with COL6A1-related disease. ClinVar contains an entry for this variant (Variation ID: 429802). 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 and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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