ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.1114AAG[2] (p.Lys374del)

dbSNP: rs745569223
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001946362 SCV002207627 uncertain significance RYR1-related disorder 2022-03-08 criteria provided, single submitter clinical testing This variant, c.1120_1122del, results in the deletion of 1 amino acid(s) of the RYR1 protein (p.Lys374del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs745569223, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 RCV002492006 SCV002800801 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 2021-10-02 criteria provided, single submitter clinical testing
GeneDx RCV005051938 SCV005685931 likely pathogenic not provided 2024-07-23 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; In-frame deletion of 1 amino acids in a non-repeat region; This variant is associated with the following publications: (PMID: 33767344)

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