ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.11600G>A (p.Arg3867His)

gnomAD frequency: 0.00002  dbSNP: rs758651267
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001234854 SCV001407514 uncertain significance RYR1-related disorder 2022-10-24 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 3867 of the RYR1 protein (p.Arg3867His). This variant is present in population databases (rs758651267, gnomAD 0.008%). 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: 961199). 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.
Fulgent Genetics, Fulgent Genetics RCV002497805 SCV002786997 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 2021-07-20 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV003132317 SCV003812574 uncertain significance not provided 2019-06-25 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004004858 SCV004822598 uncertain significance Malignant hyperthermia, susceptibility to, 1 2023-09-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV004033263 SCV004945797 uncertain significance Inborn genetic diseases 2023-10-10 criteria provided, single submitter clinical testing The c.11600G>A (p.R3867H) alteration is located in exon 83 (coding exon 83) of the RYR1 gene. This alteration results from a G to A substitution at nucleotide position 11600, causing the arginine (R) at amino acid position 3867 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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