ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.7102C>G (p.Leu2368Val)

gnomAD frequency: 0.00026  dbSNP: rs139498212
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000721639 SCV000576861 uncertain significance not provided 2022-03-03 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 12668474)
PreventionGenetics, part of Exact Sciences RCV000721639 SCV000852753 uncertain significance not provided 2016-07-11 criteria provided, single submitter clinical testing
Invitae RCV000804523 SCV000944437 uncertain significance RYR1-related disorder 2022-08-16 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2368 of the RYR1 protein (p.Leu2368Val). This variant is present in population databases (rs139498212, gnomAD 0.08%). 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: 426424). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 RCV002489191 SCV002797693 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 2021-08-30 criteria provided, single submitter clinical testing

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