ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.7742C>T (p.Ser2581Phe)

dbSNP: rs746348043
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520336 SCV000621535 uncertain significance not provided 2017-10-11 criteria provided, single submitter clinical testing The S2581F variant in the RYR1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The S2581F variant is not observed in large population cohorts (Lek et al., 2016). The S2581F variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret S2581F as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000687806 SCV000815394 uncertain significance RYR1-related disorder 2022-08-16 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 452707). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 2581 of the RYR1 protein (p.Ser2581Phe).
Revvity Omics, Revvity RCV000520336 SCV003813078 uncertain significance not provided 2019-07-02 criteria provided, single submitter clinical testing

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