ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.2870G>T (p.Gly957Val) (rs587779654)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Collagen Diagnostic Laboratory,University of Washington RCV000087684 SCV000120576 pathogenic Ehlers-Danlos syndrome, type 4 no assertion criteria provided clinical testing
Invitae RCV000087684 SCV000961962 pathogenic Ehlers-Danlos syndrome, type 4 2018-11-10 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 957 of the COL3A1 protein (p.Gly957Val). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with Ehlers-Danlos syndrome or clinical features of this disease (PMID: 24922459, Invitae). ClinVar contains an entry for this variant (Variation ID: 101446). This variant disrupts the p.Gly957 amino acid residue in COL3A1. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 24650746, 2492273), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. 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.

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