Paralogue annotation of variants is widely applicable: approximately half of all disease-associated genes have one or more paralogues with disease-causing variants.10 The technique can also be applied in a reciprocal manner, as illustrated here with RYR1 and RYR2, and our web-based application will be informative for researchers and clinicians interested in a range of diseases mediated by ion channels and membrane excitability, such as malignant hyperthermia and central core disease, and as well as the cardiovascular genetics community. This evidence concerns the gene RYR1 and Malignant hyperthermia.