Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000087470 | SCV001401705 | pathogenic | Ehlers-Danlos syndrome, type 4 | 2019-07-17 | criteria provided, single submitter | clinical testing | 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. 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: "Not Available"; Align-GVGD: "Class C65"). This variant has been observed to be de novo in an individual affected with vascular-type Ehlers-Danlos syndrome (PMID: 20518783), and it has been reported in other affected individuals (PMID: 22019127, 22610159, 24922459). ClinVar contains an entry for this variant (Variation ID: 101233). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with aspartic acid at codon 603 of the COL3A1 protein (p.Gly603Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. |
| Collagen Diagnostic Laboratory, |
RCV000087470 | SCV000120357 | pathogenic | Ehlers-Danlos syndrome, type 4 | no assertion criteria provided | clinical testing |