ClinVar Miner

Submissions for variant NM_001035.3(RYR2):c.13249G>C (p.Glu4417Gln)

gnomAD frequency: 0.00004  dbSNP: rs903232857
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002529914 SCV000760633 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1 2022-08-12 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 4417 of the RYR2 protein (p.Glu4417Gln). This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with RYR2-related conditions. ClinVar contains an entry for this variant (Variation ID: 532353). 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. 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.
Ambry Genetics RCV002386039 SCV002692974 uncertain significance Cardiovascular phenotype 2022-09-08 criteria provided, single submitter clinical testing The p.E4417Q variant (also known as c.13249G>C), located in coding exon 90 of the RYR2 gene, results from a G to C substitution at nucleotide position 13249. The glutamic acid at codon 4417 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is not well 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 RCV002492991 SCV002784147 uncertain significance Arrhythmogenic right ventricular dysplasia 2; Catecholaminergic polymorphic ventricular tachycardia 1; Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome 2021-08-24 criteria provided, single submitter clinical testing

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