ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.12823G>A (p.Ala4275Thr)

gnomAD frequency: 0.00004  dbSNP: rs761125496
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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 RCV001345564 SCV001539693 uncertain significance RYR1-related disorder 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 4275 of the RYR1 protein (p.Ala4275Thr). This variant is present in population databases (rs761125496, 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: 1041717). 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.
GeneDx RCV002267106 SCV002549283 uncertain significance not provided 2022-07-14 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV002493776 SCV002784014 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 2021-08-04 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV002267106 SCV003812481 uncertain significance not provided 2022-06-21 criteria provided, single submitter clinical testing

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