ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.13977G>A (p.Glu4659=) (rs78369334)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000249048 SCV000318661 benign Cardiovascular phenotype 2015-08-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000768789 SCV000900160 benign Cardiomyopathy 2016-11-23 criteria provided, single submitter clinical testing
Color RCV000768789 SCV000903046 benign Cardiomyopathy 2018-03-15 criteria provided, single submitter clinical testing
GeneDx RCV000036686 SCV000171437 benign not specified 2013-04-18 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Clinical Services Laboratory,Illumina RCV000232154 SCV000356483 likely benign Catecholaminergic polymorphic ventricular tachycardia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000262531 SCV000356484 likely benign Arrhythmogenic right ventricular cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588968 SCV000697611 benign not provided 2016-08-29 criteria provided, single submitter clinical testing Variant summary: The RYR2 c.13977G>A (p.Glu4659Glu) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 348/93444 control chromosomes (10 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.0391768 (316/8066). This frequency is about 1567 times the estimated maximal expected allele frequency of a pathogenic RYR2 variant (0.000025), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Invitae RCV000232154 SCV000285701 benign Catecholaminergic polymorphic ventricular tachycardia 2018-01-09 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000036686 SCV000060341 benign not specified 2012-05-24 criteria provided, single submitter clinical testing 2.9% (89/3064) of Afr Amer chrom in ESP

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