ClinVar Miner

Submissions for variant NM_001849.3(COL6A2):c.2627G>A (p.Arg876His) (rs1012567148)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000584913 SCV000693066 likely pathogenic not provided 2017-10-31 criteria provided, single submitter clinical testing
Invitae RCV000653580 SCV000775462 uncertain significance Bethlem myopathy 1 2017-12-27 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 876 of the COL6A2 protein (p.Arg876His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the heterozygous state along with a second COL6A2 variant in individuals affected with myopathy (PMID: 24271325). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). A different missense substitution at this codon (p.Arg876Ser) has been determined to be pathogenic (PMID: 4271325, 20106987, 15689448). This suggests that the arginine residue is critical for COL6A2 protein function and that other missense substitutions at this position may also be pathogenic. 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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