ArticleBritish journal of anaesthesia2016
Comparison of pathogenicity prediction tools on missense variants in RYR1 and CACNA1S associated with malignant hyperthermia.
Article in British journal of anaesthesia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 48 citations in OpenAlex.
- Relevance of pathogenicity prediction tools in human RYR1 variants of unknown significance.Scientific reports · 2021Trial
- Evaluating variant pathogenicity prediction tools to establish African inclusive guidelines for germline genetic testing.Communications medicine · 2025Article
- DTreePred: an online viewer based on machine learning for pathogenicity prediction of genomic variants.BMC bioinformatics · 2025Article
- Novel mutations in CYBB Gene Cause X-linked chronic Granulomatous Disease in Pakistani patients.Italian journal of pediatrics · 2023Article
- In vivo versus in silico assessment of potentially pathogenic missense variants in human reproductive genes.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Pharmacogenomic profile of actionable molecular variants related to drugs commonly used in anesthesia: WES analysis reveals new mutations.Frontiers in pharmacology · 2023Article
- Computational approaches for predicting variant impact: An overview from resources, principles to applications.Frontiers in genetics · 2022Review
- Genetic analysis of 39 erythrocytosis and hereditary hemochromatosis-associated genes in the Slovenian family with idiopathic erythrocytosis.Journal of clinical laboratory analysis · 2021Article
- Efficacy of computational predictions of the functional effect of idiosyncratic pharmacogenetic variants.PeerJ · 2021Article
- Functional analysis of newly identified RYR1 variants in patients susceptible to malignant hyperthermia.Journal of anesthesia · 2020Article
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- Abnormal calcium signalling and the caffeine-halothane contracture test.British journal of anaesthesia · 2019Article
- Non-traumatic and non-drug-induced rhabdomyolysis.Archives of medical sciences. Atherosclerotic diseases · 2019Article
- RYR1 and CACNA1S genetic variants identified with statin-associated muscle symptoms.Pharmacogenomics · 2018Article
- Genetic epidemiology of malignant hyperthermia in the UK.British journal of anaesthesia · 2018Article
- Myotoxicity of local anesthetics is equivalent in individuals with and without predisposition to malignant hyperthermia.Journal of anesthesia · 2018Article
- Malignant Hyperthermia in the Post-Genomics Era: New Perspectives on an Old Concept.Anesthesiology · 2018Review
- Novel Variants in Individuals withFrontiers in neurology · 2018Article
- Assessing predictions of fitness effects of missense mutations in SUMO-conjugating enzyme UBE2I.Human mutation · 2017Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMalignant hyperthermia (MH) is a pharmacogenetic disorder that has been linked to the skeletal muscle calcium release channel (RYR1) and the α1S subunit of the voltage-dependent L-type calcium channel (CACNA1S). Genomic DNA capture and next generation sequencing are becoming the preferred method to identify mutations in these genes. Bioinformatic pathogenicity prediction of identified variants may help to determine if these variants are in fact disease causing.
methodsEight pathogenicity prediction programmes freely available on the web were used to determine their ability to correctly predict the impact of a missense variant on RyR1 or dihydropyridine receptor (DHPR) protein function. We tested MH-causative variants, variants that had been shown to alter calcium release in cells, and common sequence variants in RYR1 and CACNA1S.
resultsNone of the prediction programmes was able to identify all of the variants tested correctly as either 'damaging' (MH-causative variants, variants that had been shown to alter calcium release in cells) or as 'benign' (common sequence variants). The overall sensitivity of predictions ranged from 84% to 100% depending on the programme used, with specificity from 25% to 83%.
conclusionsIn this study we determined the sensitivity and specificity of bioinformatic pathogenicity prediction tools for RYR1 and CACNA1S. We suggest that the prediction results should be treated with caution, as none of the programmes tested predicted all the variants correctly and should only be used in combination with other available data (functional assays, segregation analysis).
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