ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.9278G>A (p.Arg3093His)

gnomAD frequency: 0.00001  dbSNP: rs1414706865
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001303902 SCV001493167 uncertain significance RYR1-related disorder 2022-10-03 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 3093 of the RYR1 protein (p.Arg3093His). 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 expected to disrupt RYR1 protein function. ClinVar contains an entry for this variant (Variation ID: 1006802). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%).
Fulgent Genetics, Fulgent Genetics RCV002486173 SCV002783222 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
Revvity Omics, Revvity RCV003132390 SCV003812560 uncertain significance not provided 2021-02-12 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV001303902 SCV004106308 uncertain significance RYR1-related disorder 2023-01-11 criteria provided, single submitter clinical testing The RYR1 c.9278G>A variant is predicted to result in the amino acid substitution p.Arg3093His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0033% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/19-39002929-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Ambry Genetics RCV004036294 SCV004943174 uncertain significance Inborn genetic diseases 2024-01-08 criteria provided, single submitter clinical testing The c.9278G>A (p.R3093H) alteration is located in exon 63 (coding exon 63) of the RYR1 gene. This alteration results from a G to A substitution at nucleotide position 9278, causing the arginine (R) at amino acid position 3093 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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