Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000018757 | SCV000938015 | likely pathogenic | Ehlers-Danlos syndrome, type 4 | 2018-10-16 | 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, missense variants at 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. This variant has been observed in several individuals affected with Ehlers-Danlos syndrome or with clinical features of this disease (PMID: 1357232, 24922459, 10923041). This variant is also known as Gly1006Glu in the literature. ClinVar contains an entry for this variant (Variation ID: 17217). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with glutamic acid at codon 1173 of the COL3A1 protein (p.Gly1173Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. |
OMIM | RCV000018757 | SCV000039040 | pathogenic | Ehlers-Danlos syndrome, type 4 | 1992-01-01 | no assertion criteria provided | literature only | |
Collagen Diagnostic Laboratory, |
RCV000018757 | SCV000120230 | pathogenic | Ehlers-Danlos syndrome, type 4 | no assertion criteria provided | clinical testing |