ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.5891G>A (p.Arg1964His)

gnomAD frequency: 0.00003  dbSNP: rs767487116
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001939235 SCV002225920 uncertain significance RYR1-related disorder 2022-10-25 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 1964 of the RYR1 protein (p.Arg1964His). This variant is present in population databases (rs767487116, gnomAD 0.01%). 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: 1441339). 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 RCV002479533 SCV002800699 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 2021-09-21 criteria provided, single submitter clinical testing
Ambry Genetics RCV002563395 SCV003751283 uncertain significance Inborn genetic diseases 2021-11-08 criteria provided, single submitter clinical testing The c.5891G>A (p.R1964H) alteration is located in exon 36 (coding exon 36) of the RYR1 gene. This alteration results from a G to A substitution at nucleotide position 5891, causing the arginine (R) at amino acid position 1964 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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