ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.9892G>A (p.Ala3298Thr)

gnomAD frequency: 0.00002  dbSNP: rs544339193
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV000721762 SCV000852897 uncertain significance not provided 2017-09-11 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001312367 SCV001502816 pathogenic RYR1-related disorder 2025-01-21 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 3298 of the RYR1 protein (p.Ala3298Thr). This variant is present in population databases (rs544339193, gnomAD 0.05%). This missense change has been observed in individual(s) with clinical features of autosomal recessive RYR1-related myopathy (PMID: 28818389, 30611313; internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 590640). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt RYR1 protein function with a negative predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002485830 SCV002787777 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 2021-11-22 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000721762 SCV003810559 uncertain significance not provided 2023-10-09 criteria provided, single submitter clinical testing
Muscle and Diseases Team, Institut de Génétique et Biologie Moléculaire et Cellulaire RCV004586902 SCV005038486 likely pathogenic Centronuclear myopathy 2024-03-01 criteria provided, single submitter research PM2+PM3+PP1+PP2

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