ClinVar Miner

Submissions for variant NM_000093.4(COL5A1):c.2564C>G (p.Pro855Arg) (rs150539264)

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
Ambry Genetics RCV000621501 SCV000738586 uncertain significance Cardiovascular phenotype 2017-06-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
GeneDx RCV000199153 SCV000249806 uncertain significance not provided 2018-09-13 criteria provided, single submitter clinical testing The P855R variant of uncertain significance in the COL5A1 gene has not been published as pathogenic or been reported as benign to our knowledge. The P855R 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. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Nevertheless, while the P855R variant occurs within the triple helical region of the COL5A1 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, this variant is observed in 0.02%-0.09% alleles across ethnic groups, including one homozygous individual, in large population cohorts (Lek et al., 2016), indicating it may be a rare benign variant. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Invitae RCV000634670 SCV000756004 likely benign Ehlers-Danlos syndrome, classic type 2017-11-10 criteria provided, single submitter clinical testing

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.