ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.548G>T (p.Gly183Val)

dbSNP: rs587779420
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001972578 SCV002242713 pathogenic Ehlers-Danlos syndrome, type 4 2020-11-12 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with COL3A1-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt COL3A1 protein function. This variant disrupts the triple helix domain of COL3A1. 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, variants that affect 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 is not present in population databases (ExAC no frequency). This sequence change replaces glycine with valine at codon 183 of the COL3A1 protein (p.Gly183Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine.

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