Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000474051 | SCV000541789 | likely pathogenic | Ehlers-Danlos syndrome, type 4 | 2016-08-25 | criteria provided, single submitter | clinical testing | In summary, this variant is a novel missense change that affects one of the glycine residues within the triple helix of the COL3A1 protein. For these reasons, it has been classified as Likely Pathogenic. Glycine residues within the triple helix region are important for fibrillar collagens structure and stability (PMID: 7695699, 19344236). In the case of COL3A1 the majority of the missense substitutions at the triple helix domain affect glycine residues (PMID: 24922459, 25758994). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a COL3A1-related disease. This sequence change replaces glycine with aspartic acid at codon 771 of the COL3A1 protein (p.Gly771Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. |