ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.2194G>A (p.Gly732Arg) (rs587779606)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Translational Omics - GOSgene,University College London RCV000087561 SCV000778568 likely pathogenic Ehlers-Danlos syndrome, type 4 2018-03-16 criteria provided, single submitter clinical testing
Collagen Diagnostic Laboratory,University of Washington RCV000087561 SCV000120451 pathogenic Ehlers-Danlos syndrome, type 4 no assertion criteria provided clinical testing
Invitae RCV000087561 SCV000814061 pathogenic Ehlers-Danlos syndrome, type 4 2018-05-03 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 732 of the COL3A1 protein (p.Gly732Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with vascular Ehlers-Danlos syndrome (PMID: 22019127, 24922459). ClinVar contains an entry for this variant (Variation ID: 101323). Glycine residues within the Gly-Xaa-Yaa repeats of the triple helix domain are required for the structure and stability of fibrillar collagens (PMID: 7695699, 8218237, 19344236). In COL3A1, missense variants at these glycine residues are significantly enriched in individuals with disease (PMID: 24922459, 25758994) compared to the general population (ExAC). The observation of two more missense substitutions at this codon (p.Gly732Glu and p.Gly732Val) in affected individuals suggests that this may be a clinically significant residue (PMID: 20518783, 17728513). For these reasons, this variant has been classified as Pathogenic.

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