ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.1614G>A (p.Ala538=)

gnomAD frequency: 0.00002  dbSNP: rs566885717
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000621292 SCV000737835 likely benign Cardiovascular phenotype 2016-12-09 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV002515321 SCV000820331 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1 2023-06-17 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 201218). This variant has not been reported in the literature in individuals affected with RYR2-related conditions. This variant is present in population databases (rs566885717, gnomAD 0.0009%). This sequence change affects codon 538 of the RYR2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the RYR2 protein.
Color Diagnostics, LLC DBA Color Health RCV001179341 SCV001343988 uncertain significance Cardiomyopathy 2022-12-21 criteria provided, single submitter clinical testing This synonymous variant does not change the amino acid sequence of the RYR2 protein. Splice site prediction tools suggest that this variant may impact RNA splicing. However, this prediction has not been confirmed in published RNA studies. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/248480 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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