ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.1820C>T (p.Pro607Leu) (rs1039226542)

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 RCV000523463 SCV000621949 uncertain significance not specified 2017-10-27 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the COL3A1 gene. The P607L variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The P607L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved across species. In addition, although the P607L variant is in the triple helical region of the COL3A1 gene, it does not affect a Glycine residue in a Gly-X-Y motif, where the majority of pathogenic missense variants occur (Stenson et al., 2014; Symoens et al., 2012). Finally, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Invitae RCV000456434 SCV000541807 uncertain significance Ehlers-Danlos syndrome, type 4 2016-08-03 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 607 of the COL3A1 protein (p.Pro607Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a COL3A1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). In summary, this variant is a novel missense change with uncertain impact on protein function. It is not expected to cause disease, but 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.