ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.3554G>A (p.Gly1185Asp) (rs121912917)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Collagen Diagnostic Laboratory,University of Washington RCV000018756 SCV000120447 pathogenic Ehlers-Danlos syndrome, type 4 no assertion criteria provided clinical testing
GeneDx 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

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.