ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.13192G>A (p.Gly4398Arg)

dbSNP: rs1472582325
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001333505 SCV001526104 uncertain significance Central core myopathy 2018-07-31 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp RCV001871849 SCV002223216 uncertain significance RYR1-related disorder 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 4398 of the RYR1 protein (p.Gly4398Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with RYR1-related conditions. 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.

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