ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.9560A>G (p.Lys3187Arg) (rs184218219)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000036807 SCV000060462 likely benign not specified 2012-02-09 criteria provided, single submitter clinical testing Lys3187Arg in exon 67 of RYR2: This variant is not expected to have clinical sig nificance because it has been identified in 0.4% (12/3078) of African American c hromosomes by the NHLBI Exome Sequencing Project in a broad population (http://e vs.gs.washington.edu/EVS; dbSNP rs184218219). Lys3187Arg in exon 67 of RYR2 (rs 184218219; allele frequency = 0.4%, 12/3078) **
GeneDx RCV000036807 SCV000235012 likely benign not specified 2017-09-18 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.
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000239266 SCV000296980 likely benign Catecholaminergic polymorphic ventricular tachycardia 2015-11-30 criteria provided, single submitter clinical testing
Invitae RCV000239266 SCV000554562 benign Catecholaminergic polymorphic ventricular tachycardia 2019-12-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588751 SCV000697634 likely benign not provided 2017-03-13 criteria provided, single submitter clinical testing Variant summary: The RYR2 c.9560A>G (p.Lys3187Arg) variant involves the alteration of a conserved nucleotide but is predicted to be benign by 4/4 in silico functional prediction tools (SNPs&GO not captured due to low reliability index). This variant was found in 41/74098 control chromosomes from ExAC, predominantly observed in the African subpopulation at a frequency of 0.005859 (41/6998). This frequency is about 107 times the estimated maximal expected allele frequency of a pathogenic RYR2 variant (0.000055), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as likely benign. The variant, classified as likely benign by authors, has been reported in one patient with dilated cardiomyopathy who also carried VCL c.2862_2864delGTT and MYBPC3 p.Asp605Asn which are classified as VUS - favor pathogenic (Pugh_2014). Taken together, this variant is currently classified as Likely Benign.
Ambry Genetics RCV000620711 SCV000734935 likely benign Cardiovascular phenotype 2019-03-15 criteria provided, single submitter clinical testing Subpopulation frequency in support of benign classification;In silico models in agreement (benign)
Color RCV000777798 SCV000913790 likely benign Cardiomyopathy 2018-09-10 criteria provided, single submitter clinical testing

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