ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.13313T>G (p.Val4438Gly)

gnomAD frequency: 0.00002  dbSNP: rs1328605630
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV003106038 SCV000852343 uncertain significance RYR1-related disorder 2023-12-13 criteria provided, single submitter clinical testing The RYR1 c.13313T>G variant is predicted to result in the amino acid substitution p.Val4438Gly. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.011% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Fulgent Genetics, Fulgent Genetics RCV002507265 SCV002814488 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 2021-08-11 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003106038 SCV003782354 uncertain significance RYR1-related disorder 2022-11-01 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 4438 of the RYR1 protein (p.Val4438Gly). This variant is present in population databases (no rsID available, 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: 590429). 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.
CeGaT Center for Human Genetics Tuebingen RCV000721312 SCV004183655 uncertain significance not provided 2023-11-01 criteria provided, single submitter clinical testing RYR1: PM2

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