ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.4740G>A (p.Pro1580=) (rs79811945)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 10
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000036756 SCV000060411 benign not specified 2015-02-18 criteria provided, single submitter clinical testing p.Pro1580Pro in exon 36 of RYR2: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 5.5% (379/6868) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs79811945).
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000036756 SCV000203479 benign not specified 2013-11-26 criteria provided, single submitter clinical testing
Invitae RCV000230447 SCV000285732 benign Catecholaminergic polymorphic ventricular tachycardia 2019-12-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000036756 SCV000306062 likely benign not specified criteria provided, single submitter clinical testing
Ambry Genetics RCV000251724 SCV000318244 benign Cardiovascular phenotype 2016-03-03 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Illumina Clinical Services Laboratory,Illumina RCV001093875 SCV000356297 benign Catecholaminergic polymorphic ventricular tachycardia type 1 2018-01-12 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000260040 SCV000356298 benign Arrhythmogenic right ventricular dysplasia, familial, 2 2018-01-12 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000768767 SCV000900137 benign Cardiomyopathy 2016-06-12 criteria provided, single submitter clinical testing
Color RCV000768767 SCV000902736 benign Cardiomyopathy 2018-03-16 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000036756 SCV001363327 benign not specified 2019-03-18 criteria provided, single submitter clinical testing Variant summary: RYR2 c.4740G>A alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0032 in 273374 control chromosomes, predominantly at a frequency of 0.042 within the East Asian subpopulation in the gnomAD database, including 10 homozygotes. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 1680-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in RYR2 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. To our knowledge, no occurrence of c.4740G>A in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as benign.

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.