ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.2194G>A (p.Gly732Arg)

dbSNP: 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
Labcorp Genetics (formerly Invitae), Labcorp RCV000087561 SCV000814061 pathogenic Ehlers-Danlos syndrome, type 4 2018-04-19 criteria provided, single submitter clinical testing 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). 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). For these reasons, this variant has been classified as Pathogenic. 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). This variant is not present in population databases (ExAC no frequency). 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.
Collagen Diagnostic Laboratory, University of Washington RCV000087561 SCV000120451 pathogenic Ehlers-Danlos syndrome, type 4 no assertion criteria provided clinical testing

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