ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.8749A>G (p.Ile2917Val)

gnomAD frequency: 0.00002  dbSNP: rs981753891
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002551436 SCV001202545 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1 2022-10-17 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RYR2 protein function. ClinVar contains an entry for this variant (Variation ID: 837653). This variant has not been reported in the literature in individuals affected with RYR2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2917 of the RYR2 protein (p.Ile2917Val).
Ambry Genetics RCV002372763 SCV002687762 uncertain significance Cardiovascular phenotype 2021-08-10 criteria provided, single submitter clinical testing The p.I2917V variant (also known as c.8749A>G), located in coding exon 60 of the RYR2 gene, results from an A to G substitution at nucleotide position 8749. The isoleucine at codon 2917 is replaced by valine, an amino acid with highly similar properties. This variant was detected in an exome cohort with limited clinical details provided (Landstrom AP et al. Circ Arrhythm Electrophysiol, 2017 Apr;10:[Epub]). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002497365 SCV002789672 uncertain significance Arrhythmogenic right ventricular dysplasia 2; Catecholaminergic polymorphic ventricular tachycardia 1; Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome 2022-03-03 criteria provided, single submitter clinical testing

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