ClinVar Miner

Submissions for variant NM_000393.5(COL5A2):c.1633C>T (p.Arg545Trp) (rs145258293)

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
GeneDx RCV000198486 SCV000249960 uncertain significance not provided 2018-04-25 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the COL5A2 gene. Although the R545W variant has not been published as pathogenic or been reported as benign to our knowledge, it has been identified independently and in conjunction with additional cardiogenetic variants in individuals referred for HDCT genetic testing at GeneDx. However, thus far, segregation data is limited for these individuals due to the lack of clinical information provided and insufficient participation by informative family members. The R545W 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. Moreover, in-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Nevertheless, the R545W variant 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). Additionally, the R545W variant is observed 46/276,944 global alleles (0.02%) in large population cohorts (Lek et al., 2016).
Invitae RCV001084506 SCV000547878 likely benign Ehlers-Danlos syndrome, classic type 2019-12-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001139414 SCV001299565 likely benign Ehlers-Danlos syndrome classic type 2 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

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.