ClinVar Miner

Submissions for variant NM_001849.3(COL6A2):c.2527C>T (p.Arg843Trp) (rs376880198)

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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 RCV000597570 SCV000701563 uncertain significance not provided 2016-12-19 criteria provided, single submitter clinical testing
Invitae RCV000801298 SCV000941069 uncertain significance Bethlem myopathy 1 2019-09-13 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 843 of the COL6A2 protein (p.Arg843Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs376880198, ExAC 0.01%). This variant has been observed in combination with additional COL6A2 variants in an individual affected with Bethlem myopathy (PMID: 19949035). This variant has also been observed in an individual affected with limb-girdle muscular dystrophy (PMID: 30564623). ClinVar contains an entry for this variant (Variation ID: 242692). 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Arg843 amino acid residue in COL6A2. Other variant(s) that disrupt this residue (p.Arg843Gln) have been observed in individuals with COL6A2-related conditions (PMID: 24271325), which suggests that this may be a clinically significant amino acid residue. 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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