ClinVar Miner

Submissions for variant NM_004369.3(COL6A3):c.1867C>T (p.Pro623Ser) (rs372022185)

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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 RCV000726933 SCV000704269 uncertain significance not provided 2017-12-12 criteria provided, single submitter clinical testing
GeneDx RCV000413959 SCV000491859 uncertain significance not specified 2016-11-16 criteria provided, single submitter clinical testing The P623S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The P623S 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 RCV000704566 SCV000833519 uncertain significance Bethlem myopathy 1 2018-06-18 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 623 of the COL6A3 protein (p.Pro623Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs372022185, ExAC 0.02%). This variant has not been reported in the literature in individuals with COL6A3-related disease. ClinVar contains an entry for this variant (Variation ID: 373274). 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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