ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.3175C>T (p.Pro1059Ser)

gnomAD frequency: 0.00003  dbSNP: rs558190898
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000332933 SCV000335723 uncertain significance not provided 2015-10-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001859581 SCV002145308 uncertain significance RYR1-related disorder 2021-10-17 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 1059 of the RYR1 protein (p.Pro1059Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs558190898, ExAC 0.01%). This variant has not been reported in the literature in individuals with RYR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 283543). 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 RCV002487208 SCV002788585 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 2021-10-21 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000332933 SCV003815011 uncertain significance not provided 2022-04-21 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV001859581 SCV004120913 uncertain significance RYR1-related disorder 2022-12-15 criteria provided, single submitter clinical testing The RYR1 c.3175C>T variant is predicted to result in the amino acid substitution p.Pro1059Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.018% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/19-38957035-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
All of Us Research Program, National Institutes of Health RCV003995765 SCV004833825 uncertain significance Malignant hyperthermia, susceptibility to, 1 2023-05-23 criteria provided, single submitter clinical testing

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