ClinVar Miner

Submissions for variant NM_001849.3(COL6A2):c.643G>A (p.Asp215Asn) (rs563449281)

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
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000386796 SCV000342528 uncertain significance not provided 2017-06-02 criteria provided, single submitter clinical testing
Invitae RCV000526278 SCV000657214 uncertain significance Bethlem myopathy 1 2016-08-01 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 215 of the COL6A2 protein (p.Asp215Asn). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs563449281, ExAC 0.01%). This variant occurs outside of the conserved triple-helical domain of the type 6 alpha-2 collagen protein where amino acid substitutions are rarely pathogenic. This variant has been reported a single family affected with progressive myoclonus epilepsy (PMID: 23138527). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The asparagine amino acid residue is also found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. Algorithms developed to predict the effect of sequence changes on mRNA splicing suggest that this variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a rare missense change with uncertain impact on protein function and mRNA splicing. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role in disease. 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.