Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000434900 | SCV000521085 | likely pathogenic | not provided | 2016-08-12 | criteria provided, single submitter | clinical testing | The G1185D variant in the COL3A1 gene has been reported previously (as G1018D due to the use of alternative nomenclature) in association with Ehlers-Danlos syndrome, vascular type (Pepin et al., 2014; Kontusaari et al., 1992). This variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G1185D variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in the same residue (G1185V, reported as G1018V due to the use of alternative nomenclature) has been reported in association with Ehlers-Danlos syndrome vascular type (Smith et al., 1997), supporting the functional importance of this region of the protein. The G1185D variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded. |
| OMIM | RCV000018756 | SCV000039039 | pathogenic | Ehlers-Danlos syndrome, type 4 | 1992-09-01 | no assertion criteria provided | literature only | |
| Collagen Diagnostic Laboratory, |
RCV000018756 | SCV000120447 | pathogenic | Ehlers-Danlos syndrome, type 4 | no assertion criteria provided | clinical testing |