ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.10725+4A>T (rs116444428)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769801 SCV000901227 uncertain significance Cardiomyopathy 2016-06-29 criteria provided, single submitter clinical testing
Invitae RCV001065668 SCV001230638 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 2019-12-30 criteria provided, single submitter clinical testing This sequence change falls in intron 75 of the RYR2 gene. It does not directly change the encoded amino acid sequence of the RYR2 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs116444428, ExAC 0.008%). This variant has not been reported in the literature in individuals with RYR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 626623). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies and prediction algorithms are not available or were not evaluated, and the effect of this variant on mRNA splicing is currently unknown. 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.
Illumina Clinical Services Laboratory,Illumina RCV001101643 SCV001258268 uncertain significance Catecholaminergic polymorphic ventricular tachycardia type 1 2018-01-19 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 RCV001101644 SCV001258269 uncertain significance Arrhythmogenic right ventricular dysplasia, familial, 2 2018-01-19 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.
Color RCV000769801 SCV001360077 likely benign Cardiomyopathy 2018-11-16 criteria provided, single submitter clinical testing

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