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Updated: Mar 19, 2026

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
Rare variants in known and novel candidate genes predisposing to statin-associated myopathy
Magdaléna Neřoldová1, Viktor Stránecký2, Kateřina Hodaňová2
1Laboratory of Experimental Hepatology, Center for Experimental Medicine, Institute for Clinical & Experimental Medicine, Prague, Czech Republic.
Aim:
Genetic variants affecting statin uptake, metabolism or predisposing to muscular diseases may confer susceptibility to statin-induced myopathy. Besides the SLCO1B1 rs4149056 genotype, common genetic variants do not seem to determine statin-associated myopathy. Here we aimed to address the potential role of rare variants.
Methods:
We performed whole exome sequencing in 88 individuals suffering from statin-associated myopathy and assessed the burden of rare variants using candidate-gene and exome-wide association analysis.
Results:
In the novel candidate gene CLCN1, we identified a heterozygote truncating mutation p.R894* in four patients. In addition, we detected predictably pathogenic case-specific variants in MYOT, CYP3A5, SH3TC2, FBXO32 and RBM20.
Conclusion:
These findings support the role of rare variants and nominate loci for follow-up studies.
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