ClinVar Miner

Submissions for variant NM_001848.2(COL6A1):c.841G>A (p.Gly281Arg) (rs267606746)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000497629 SCV000589652 pathogenic not provided 2017-05-17 criteria provided, single submitter clinical testing The G281R variant in the COL6A1 gene has been reported previously in association with COL6A1-related disorders (Lampe et al., 2005; Jimenez-Mallebrera et al., 2006; Nadeau et al., 2009; Butterfield et al., 2013). Two reported individuals were found to be de novo for the G281R variant (Jimenez-Mallebrera et al., 2006; Butterfield et al., 2013). The G281R variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G281R 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. Additionally, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, missense variants at the same position (G281A, G281E) and in nearby residues (G275E, G284R) have been reported in the Human Gene Mutation Database in association with COL6A1-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, G281R is considered a pathogenic variant.
OMIM RCV000018722 SCV000039005 pathogenic Ullrich congenital muscular dystrophy 1 2009-07-07 no assertion criteria provided literature only

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