ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.12881C>T (p.Thr4294Met) (rs587784372)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000147411 SCV000194799 uncertain significance not provided 2014-01-23 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000147411 SCV000340017 uncertain significance not provided 2017-09-27 criteria provided, single submitter clinical testing
GeneDx RCV000346113 SCV000617752 uncertain significance not specified 2017-06-02 criteria provided, single submitter clinical testing The T4294M variant in the RYR1 gene has been reported previously in one African American individual who experienced a single episode of exertional rhabdomyolysis with myoglubinuria, and showed a positive contracture response to both caffeine and halothane (Sambuughin et al., 2009). This individual also harbored three other RYR1 variants (phase unknown) and T4294M was noted to be absent in 230 control subjects of varying ethnicity (Sambuughin et al., 2009). Adequate data is not available in large population cohorts to assess the frequency of this variant in publicly available databases; however, the T4294M variant is observed in 28/69900 (0.04%) alleles from presumably healthy individuals tested at GeneDx. The T4294M 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 not conserved. In silico analysis predicts this variant likely does not alter the protein structure/function. We interpret T4294M as a variant of uncertain significance.
Invitae RCV001085481 SCV000659801 likely benign RYR1-Related Disorders 2020-12-02 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000147411 SCV000852323 uncertain significance not provided 2016-02-15 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001131811 SCV001291448 uncertain significance Central core myopathy 2019-01-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001131812 SCV001291449 uncertain significance Malignant hyperthermia, susceptibility to, 1 2019-01-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001131813 SCV001291450 uncertain significance Minicore myopathy with external ophthalmoplegia 2019-01-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Ambry Genetics RCV001266698 SCV001444875 uncertain significance Inborn genetic diseases 2016-03-04 criteria provided, single submitter clinical testing

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