ClinVar Miner

Submissions for variant NM_000393.5(COL5A2):c.2408T>C (p.Leu803Ser) (rs149737825)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000196007 SCV000250013 uncertain significance not provided 2018-03-06 criteria provided, single submitter clinical testing The L803S variant of uncertain significance in the COL5A2 gene has not been published as pathogenic or been reported as benign to our knowledge. This variant is observed in 14/66,672 alleles (0.02%) from individuals of European ancestry in the Exome Aggregation Consortium (ExAC) data set (Lek et al., 2016). The L803S 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. Although this substitution occurs at a position where amino acids with similar properties to leucine are tolerated across species, serine is not tolerated at this position in any species. Furthermore, in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, the L803S does not affect a Glycine residue in a Gly-X-Y motif in the triple helical region of the COL5A2 gene, where the majority of pathogenic missense variants occur (Stenson et al., 2014; Symoens et al., 2012).
Invitae RCV000468272 SCV000547894 uncertain significance Ehlers-Danlos syndrome, classic type 2018-10-25 criteria provided, single submitter clinical testing This sequence change replaces leucine with serine at codon 803 of the COL5A2 protein (p.Leu803Ser). The leucine residue is highly conserved and there is a large physicochemical difference between leucine and serine. This variant is present in population databases (rs149737825, ExAC 0.02%) but has not been reported in the literature in individuals with a COL5A2-related disease. ClinVar contains an entry for this variant (Variation ID: 213150). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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.