Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000087380 | SCV004293005 | pathogenic | Ehlers-Danlos syndrome, type 4 | 2023-11-20 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 300 of the COL3A1 protein (p.Gly300Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of vascular Ehlers-Danlos syndrome (PMID: 30793832; Invitae). ClinVar contains an entry for this variant (Variation ID: 101143). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. |
Collagen Diagnostic Laboratory, |
RCV000087380 | SCV000120262 | pathogenic | Ehlers-Danlos syndrome, type 4 | no assertion criteria provided | clinical testing |