ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.14270G>A (p.Arg4757His) (rs768360593)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000721359 SCV000339056 uncertain significance not provided 2016-01-20 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000293888 SCV000413016 uncertain significance Neuromuscular disease, congenital, with uniform type 1 fiber 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000351106 SCV000413017 uncertain significance Malignant hyperthermia, susceptibility to, 1 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000389289 SCV000413018 uncertain significance Minicore myopathy 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000287938 SCV000413019 uncertain significance Central core myopathy 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000721359 SCV000576933 uncertain significance not provided 2018-09-27 criteria provided, single submitter clinical testing The R4757H variant in the RYR1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R4757H variant is observed in 18/111538 (0.016%) alleles from individuals of non-Finnish European background, in large population cohorts (Lek et al., 2016). The R4757H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. We interpret R4757H as a variant of uncertain significance.
Invitae RCV000539271 SCV000659843 likely benign RYR1-Related Disorders 2019-12-23 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000721359 SCV000852400 uncertain significance not provided 2013-10-30 criteria provided, single submitter clinical testing

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