ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.10520C>T (p.Thr3507Met)

gnomAD frequency: 0.00004  dbSNP: rs371839408
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics, Fulgent Genetics RCV002493509 SCV002777193 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 2021-07-29 criteria provided, single submitter clinical testing
Invitae RCV002541762 SCV003018087 uncertain significance RYR1-related disorder 2022-10-18 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 3507 of the RYR1 protein (p.Thr3507Met). This variant is present in population databases (rs371839408, 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: 992818). 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.
Institute of Human Genetics, University of Wuerzburg RCV001281577 SCV001468887 uncertain significance Myopathy no assertion criteria provided clinical testing

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