2014). The change in amino acid structure may also interfere with DHPR calcium flux. Due to the phenotypic overlap with RYR1 pathogenic variants in F045, we hypothesize that the p.Gln1265His variant disrupts DHPR and RYR-1 coupling. While pathogenic variants in CACNA1S have been demonstrated as the cause of MHS and HOKPP1, to our knowledge, this is the first reported case of severe congenital myopathy with ophthalmoplegia resulting from pathogenic variants in CACNA1S. The gene discussed is QDPR; the disease is congenital myopathy with cores.