ClinVar Miner

Submissions for variant NM_004370.6(COL12A1):c.4723A>G (p.Arg1575Gly) (rs1490798316)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520015 SCV000618927 uncertain significance not provided 2017-07-17 criteria provided, single submitter clinical testing The R1575G variant in the COL12A1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R1575G variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R1575G 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. However, this substitution occurs at a position that is not conserved across species, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R1575G as a variant of uncertain significance.
Invitae RCV000805659 SCV000945623 uncertain significance Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2 2018-07-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 1575 of the COL12A1 protein (p.Arg1575Gly). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with COL12A1-related disease. ClinVar contains an entry for this variant (Variation ID: 450355). 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: "Deleterious"; PolyPhen-2: "Benign"; 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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