ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.12159G>A (p.Glu4053=) (rs41267517)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000036671 SCV000060326 likely benign not specified 2015-06-09 criteria provided, single submitter clinical testing p.Glu4053Glu in exon 90 of RYR2: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 0.1% (88/65298) o f European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs41267517).
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724810 SCV000233209 uncertain significance not provided 2015-05-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV000247809 SCV000318406 likely benign Cardiovascular phenotype 2016-03-30 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign
Illumina Clinical Services Laboratory,Illumina RCV001093786 SCV000356453 likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000349414 SCV000356454 uncertain significance 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, 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.
Invitae RCV000280428 SCV000554590 benign Catecholaminergic polymorphic ventricular tachycardia 2019-12-31 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000724810 SCV000884472 likely benign not provided 2018-06-29 criteria provided, single submitter clinical testing The p.Glu4053Glu variant (rs41267517) does not alter the amino acid sequence of the RYR2 protein and computational splice site prediction algorithms do not predict a change in the nearest splice site or creation of a cryptic splice site. This variant has not been reported in association with cardiac disease in medical literature or in gene specific variation databases. This variant is listed in the Genome Aggregation Database (gnomAD) with a frequency of 0.2 percent in the European Non-Finnish population (identified on 229 out of 125,998 chromosomes) and has been reported to the ClinVar database (Variation ID: 43719). Based on these observations, the p.Glu4053Glu variant is likely to be benign.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769809 SCV000901235 benign Cardiomyopathy 2018-04-30 criteria provided, single submitter clinical testing
Color RCV000769809 SCV000902958 likely benign Cardiomyopathy 2018-04-16 criteria provided, single submitter clinical testing

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