ClinVar Miner

Submissions for variant NM_000393.5(COL5A2):c.1697C>T (p.Pro566Leu) (rs1051400743)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520286 SCV000621979 uncertain significance not provided 2017-11-01 criteria provided, single submitter clinical testing The P566L variant in the COL5A2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P566L variant is not observed in large population cohorts (Lek et al., 2016). The P566L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P566L as a variant of uncertain significance.
Invitae RCV000559924 SCV000631569 uncertain significance Ehlers-Danlos syndrome, classic type 2017-07-07 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 566 of the COL5A2 protein (p.Pro566Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with COL5A2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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