Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001043150 | SCV001206867 | likely pathogenic | Ehlers-Danlos syndrome, type 4 | 2020-02-24 | criteria provided, single submitter | clinical testing | In summary, this variant is a novel missense change affecting a residue that is known to be critical for normal protein structure, stability and function. This type of missense change is also highly enriched in affected individuals and expected to be pathogenic. However, without additional functional and/or genetic data, this variant has been classified as Likely Pathogenic. 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, missense variants at these glycine residues are significantly enriched in individuals with disease (PMID: 24922459, 25758994) compared to the general population (ExAC). This variant has not been reported in the literature in individuals with COL3A1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with aspartic acid at codon 747 of the COL3A1 protein (p.Gly747Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. |