The Cav1.1 p.T1009K variant is a novel pathogenic variant for malignant hyperthermia

The genetic susceptibility to malignant hyperthermia (MH) results from variants in the RYR1 and CACNA1S genes. The majority (48) of these diagnostic variants are in RYR1, with only two in CACNA1S. We have previously identified the novel CACNA1S variant c.3026C>A (p.T1009K) as potentially pathogenic for MH,1,2 but it has not yet been functionally characterised. We have thus generated a knock-in mouse line expressing the isogenic mutation p.T1009K, and we investigated whether it has an MH phenotype.