A third mechanism of disease for RYR1-related myopathies is associated with a decrease in the overall RYR1 protein levels; this is usually correlated with the presence of compound heterozygous mutations, where the first mutation causes a premature termination codon and the second is a missense mutation (Monnier et al., 2008; Bevilacqua et al., 2011; Cacheux et al., 2015; Brennan et al., 2019). Here, RYR1 is linked to myopathy.