ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.3311C>T (p.Ala1104Val)

gnomAD frequency: 0.00007  dbSNP: rs149096607
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000535315 SCV000659914 uncertain significance RYR1-related disorder 2022-11-01 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1104 of the RYR1 protein (p.Ala1104Val). This variant is present in population databases (rs149096607, gnomAD 0.007%). 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: 478222). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RYR1 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a 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.
Ambry Genetics RCV000623053 SCV000741381 uncertain significance Inborn genetic diseases 2016-04-15 criteria provided, single submitter clinical testing
MGZ Medical Genetics Center RCV002289772 SCV002580557 uncertain significance Malignant hyperthermia, susceptibility to, 1 2021-12-29 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002491119 SCV002782412 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 2021-08-12 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV002289772 SCV004828544 uncertain significance Malignant hyperthermia, susceptibility to, 1 2023-09-05 criteria provided, single submitter clinical testing

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