ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.6385G>A (p.Asp2129Asn)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000691284 SCV000819036 uncertain significance RYR1-Related Disorders 2018-04-05 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 2129 of the RYR1 protein (p.Asp2129Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs772695891, ExAC 0.01%). This variant has been reported in the literature in an individual affected with exercise induced rhabdomyolysis and was absent in that individual's unaffected family members (PMID: 25960145). In addition, a different variant (c.6387C>G) giving rise to the same protein effect observed here (p.Asp2129Asn) has been reported in an individual affected with malignant hyperthermia (PMID: 11241852). 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 C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. 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.