EMQN Best Practice Guidelines for Genetic Testing and Reporting in RYR1-related disorders.

Context-dependent interpretation of RYR1 variants according to functional domain

The first EMQN best practice guidelines for genetic testing and reporting in RYR1-related disorders are published, covering malignant hyperthermia, exertional rhabdomyolysis, and both dominant and recessive congenital myopathies. Guidelines emphasize context-dependent RYR1 variant interpretation: gain-of-function variants associate with MH susceptibility, while dominant-negative and loss-of-function variants associate with myopathies. A subset of variants confer combined dominant MH susceptibility with myopathy, posing particular interpretive challenges for clinical genetics laboratories.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

These guidelines fill an important practical gap for European laboratories. The most clinically impactful point is the delineation of dual-phenotype variants (MH + myopathy) whose interpretation requires complete clinical context. For anesthesiologists, incidental identification of a gain-of-function RYR1 variant should systematically prompt MH risk counseling.

Clinical impact: 2/3 · Evidence quality: 1/3 · Novelty: 1/2 · Sample size: 1/1 · Journal quality: 1/1 → Total: 6/10