ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.828A>G (p.Arg276=) (rs180711819)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000361184 SCV000356197 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.
Illumina Clinical Services Laboratory,Illumina RCV001093847 SCV000356198 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.
GeneDx RCV000432303 SCV000514431 likely benign not specified 2017-07-14 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.
Invitae RCV000268927 SCV000637621 benign Catecholaminergic polymorphic ventricular tachycardia 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000621348 SCV000737729 likely benign Cardiovascular phenotype 2016-09-23 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000768757 SCV000900127 likely benign Cardiomyopathy 2016-06-24 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000432303 SCV000918164 benign not specified 2018-02-06 criteria provided, single submitter clinical testing Variant summary: RYR2 c.828A>G alters a non-conserved nucleotide resulting in a synonymous change (p.Arg276Arg) and 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The observed variant frequency within African control individuals in the gnomAD database is approximately 48-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in RYR2 causing Arrhythmia phenotype (6e-05), strongly suggesting that the variant is a benign polymorphism found primarily in population(s) of African origin. To our knowledge, the variant, c.828A>G, has not been reported in affected individuals via publications. However, multiple clinical diagnostic laboratories via ClinVar submissions (evaluated after 2014) classify the variant as "likely benign/benign" or "uncertain significance". Based on the evidence outlined above, the variant was classified as benign.
Color RCV000768757 SCV001343046 benign Cardiomyopathy 2018-11-08 criteria provided, single submitter clinical testing

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