ClinVar Miner

Submissions for variant NM_001854.4(COL11A1):c.4538G>A (p.Gly1513Asp) (rs1553193913)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523421 SCV000617761 likely pathogenic not provided 2017-08-10 criteria provided, single submitter clinical testing The G1513D variant in the COL11A1 gene been reported previously in an individual with Stickler syndrome (Richards et al., 2010). The G1513D variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G1513D 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, affecting a Glycine residue in the Gly-X-Y repetitive motif of the triple helical region of the COL11A1 gene. In this domain, the Glycine in the triplet repeat is critical for protein folding and substitution of a triplet Glycine is a known pathogenic mechanism (Stenson et al., 2014). In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby Glycine residues (G1507D, G1516V) have been reported in the Human Gene Mutation Database in association with COL11A1-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret G1513D as a likely pathogenic variant.

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.