ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.13271A>C (p.Glu4424Ala)

gnomAD frequency: 0.00003  dbSNP: rs752665367
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000721311 SCV000233218 uncertain significance not provided 2015-05-19 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV000721311 SCV000852342 uncertain significance not provided 2013-10-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001307331 SCV001496736 uncertain significance RYR1-related disorder 2022-09-27 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 4424 of the RYR1 protein (p.Glu4424Ala). This variant is present in population databases (rs752665367, gnomAD 0.05%). 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: 199213). 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 RCV002478601 SCV002783242 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 2021-09-08 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000721311 SCV003814450 uncertain significance not provided 2022-10-11 criteria provided, single submitter clinical testing

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