ClinVar Miner

Submissions for variant NM_004369.3(COL6A3):c.6749C>T (p.Pro2250Leu) (rs140728855)

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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 RCV000724744 SCV000228360 uncertain significance not provided 2017-02-03 criteria provided, single submitter clinical testing
GeneDx RCV000724744 SCV000536551 uncertain significance not provided 2017-01-30 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the COL6A3 gene. The P2250L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P2250L variant is observed in 11/53162 (0.02%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P2250L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, this substitution occurs at a position that is not conserved. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000794513 SCV000933925 uncertain significance Bethlem myopathy 1 2018-12-24 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 2250 of the COL6A3 protein (p.Pro2250Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs140728855, 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: 195970). 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: "Not Available"; 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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