ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.4445G>A (p.Arg1482His) (rs373024059)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000171763 SCV000050703 likely benign not provided 2013-06-24 criteria provided, single submitter research
GeneDx RCV000171763 SCV000235103 uncertain significance not provided 2016-11-15 criteria provided, single submitter clinical testing The R1482H variant of uncertain significance in the RYR2 gene has not been published as a pathogenic or benign variant to our knowledge. This variant has been identified independently and in conjunction with additional cardiogenetic variants in individuals referred for cardiomyopathy and arrhythmia genetic testing at GeneDx; however, thus far, segregation data is absent for these individuals due to the lack of clinical information provided and insufficient participation by informative family members. This variant was not observed with any significant frequency in approximately 6,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. Although this substitution occurs at a position that is conserved through mammals, the R1482H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Furthermore, the R1482H variant is not located in one of the three hot-spot regions of the RYR2 gene, where the majority of pathogenic missense variants occur (Medeiros-Domingo et al., 2009). Nevertheless, in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000212979 SCV000272388 likely benign not specified 2018-04-10 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
Invitae RCV001086924 SCV000541696 likely benign Catecholaminergic polymorphic ventricular tachycardia 2019-12-31 criteria provided, single submitter clinical testing
Color RCV000773225 SCV000906837 likely benign Cardiomyopathy 2018-04-26 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001098955 SCV001255357 uncertain significance Arrhythmogenic right ventricular dysplasia, familial, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Clinical Services Laboratory,Illumina RCV001100766 SCV001257302 likely benign Catecholaminergic polymorphic ventricular tachycardia type 1 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.