Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000087602 | SCV001216794 | likely pathogenic | Ehlers-Danlos syndrome, type 4 | 2019-08-22 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with glutamic acid at codon 309 of the COL3A1 protein (p.Gly309Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with vasculat Ehlers-Danlos syndrome (PMID: 24922459). ClinVar contains an entry for this variant (Variation ID: 101364). 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). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Collagen Diagnostic Laboratory, |
RCV000087602 | SCV000120492 | pathogenic | Ehlers-Danlos syndrome, type 4 | no assertion criteria provided | clinical testing |