Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000087649 | SCV001387728 | pathogenic | Ehlers-Danlos syndrome, type 4 | 2019-06-03 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 has been observed in individuals with clinical features of Ehlers Danlos syndrome, type IV, being de novo in one of them (PMID: 24922459, Invitae). ClinVar contains an entry for this variant (Variation ID: 101411). This sequence change replaces glycine with arginine at codon 963 of the COL3A1 protein (p.Gly963Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). |
| Collagen Diagnostic Laboratory, |
RCV000087649 | SCV000120541 | pathogenic | Ehlers-Danlos syndrome, type 4 | no assertion criteria provided | clinical testing |