ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.9634G>A (p.Glu3212Lys)

gnomAD frequency: 0.00014  dbSNP: rs185371036
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000543837 SCV000660095 uncertain significance RYR1-related disorder 2024-01-13 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 3212 of the RYR1 protein (p.Glu3212Lys). This variant is present in population databases (rs185371036, gnomAD 0.04%). 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: 478301). 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 with a negative predictive value of 95%. 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.
Mayo Clinic Laboratories, Mayo Clinic RCV001508858 SCV001715275 uncertain significance not provided 2019-07-22 criteria provided, single submitter clinical testing
GeneDx RCV001508858 SCV001783680 uncertain significance not provided 2021-03-11 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV002483520 SCV002792953 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 2021-08-11 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV001508858 SCV003812557 uncertain significance not provided 2020-03-09 criteria provided, single submitter clinical testing
Ambry Genetics RCV003159954 SCV003871932 uncertain significance Inborn genetic diseases 2023-03-07 criteria provided, single submitter clinical testing The c.9634G>A (p.E3212K) alteration is located in exon 65 (coding exon 65) of the RYR1 gene. This alteration results from a G to A substitution at nucleotide position 9634, causing the glutamic acid (E) at amino acid position 3212 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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