ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.3352G>A (p.Glu1118Lys)

gnomAD frequency: 0.00005  dbSNP: rs578234912
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000696584 SCV000825149 uncertain significance RYR1-related disorder 2022-08-09 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1118 of the RYR1 protein (p.Glu1118Lys). This variant is present in population databases (rs578234912, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 574610). 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 RYR1 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.
GeneDx RCV002293474 SCV002586621 uncertain significance not provided 2022-10-24 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV002493208 SCV002797737 uncertain significance Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; Congenital myopathy with fiber type disproportion; King Denborough syndrome 2021-08-23 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV000696584 SCV004114619 uncertain significance RYR1-related disorder 2022-11-18 criteria provided, single submitter clinical testing The RYR1 c.3352G>A variant is predicted to result in the amino acid substitution p.Glu1118Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.016% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/19-38958423-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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