ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.2686C>T (p.Arg896Trp)

gnomAD frequency: 0.00001  dbSNP: rs371050482
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001370235 SCV001566702 uncertain significance RYR1-related disorder 2022-07-26 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 896 of the RYR1 protein (p.Arg896Trp). This variant is present in population databases (rs371050482, gnomAD 0.006%). 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: 1060765). 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. 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.
GeneDx RCV001785813 SCV002027934 uncertain significance not provided 2021-08-30 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 22473935, 20681998)
Fulgent Genetics, Fulgent Genetics RCV002488158 SCV002788714 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 2021-08-03 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV001785813 SCV003812396 uncertain significance not provided 2020-02-20 criteria provided, single submitter clinical testing

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