ClinVar Miner

Submissions for variant NM_004369.3(COL6A3):c.1150G>A (p.Ala384Thr) (rs374267444)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724219 SCV000230231 uncertain significance not provided 2016-11-10 criteria provided, single submitter clinical testing
GeneDx RCV000724219 SCV000589726 uncertain significance not provided 2017-06-15 criteria provided, single submitter clinical testing The A384T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The A384T variant is observed in 5/10174 (0.05%) alleles from individuals of African background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This 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. This substitution occurs at a position that is conserved in mammals; however, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with COL6A3-related disorders (Stenson et al., 2014). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Invitae RCV000822172 SCV000962963 uncertain significance Bethlem myopathy 1 2018-11-08 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 384 of the COL6A3 protein (p.Ala384Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs374267444, ExAC 0.05%). This variant has not been reported in the literature in individuals with COL6A3-related disease. ClinVar contains an entry for this variant (Variation ID: 197233). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; 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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