Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000087682 | SCV004368676 | pathogenic | Ehlers-Danlos syndrome, type 4 | 2023-09-10 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly741 amino acid residue in COL3A1. Other variant(s) that disrupt this residue have been observed in individuals with COL3A1-related conditions (PMID: 25526469, 29323927), which suggests that this may be a clinically significant amino acid residue. 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). 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. ClinVar contains an entry for this variant (Variation ID: 101444). This missense change has been observed in individuals with vascular Ehlers-Danlos syndrome (PMID: 24399159, 30474650). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 741 of the COL3A1 protein (p.Gly741Ser). |
| Collagen Diagnostic Laboratory, |
RCV000087682 | SCV000120574 | pathogenic | Ehlers-Danlos syndrome, type 4 | no assertion criteria provided | clinical testing |