CPIC® Guideline for Potent Volatile Anesthetic Agents and Succinylcholine and RYR1 and CACNA1S

Most recent guideline publication:

Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for the use of potent volatile anesthetic agents and succinylcholine in the context of RYR1 or CACNA1S genotypes

Updates since publication:

November 2021: Subsequent to the publication of the CPIC guideline for RYR1 and malignant hyperthermia (PMID 30499100), the ClinGen variant curation expert panel (VCEP) developed and published recommendations for RYR1 pathogenicity classifications in malignant hyperthermia susceptibility. These revised ACMG/AMP criteria were applied to the 44 variants originally included in the CPIC recommendations and 29 variants were classified as pathogenic, 13 as likely pathogenic, and 2 as variants of uncertain significance (PMID 33767344). Based on this classification, the assignment for the variants c.1589G>A p.(Arg530His) and c.1598G>A p.(Arg533His) has been changed from “malignant hyperthermia-associated” to “uncertain function” in the RYR1 allele functionality table. Additional variants beyond these 44 have been identified by the VCEP and the current CPIC authors are reviewing these variants for inclusion in the CPIC tables.

September 2019: The published version of this article included a typographical error in Table 1 and in the supplemental tables: RYR1 c.488G>A should instead be listed as RYR1 c.488G>T. The Table 1 in guideline, RYR1 allele definition table, RYR1 allele functionality table, and RYR1 frequency table have been updated accordingly.

Tables provided in the main manuscript of the guideline:

Table 1. Assignment of RYR1 and CACNA1S phenotype based on genotype

Table 2. Recommended therapeutic use of inhaled anesthetics and succinylcholine in relation to RYR1 and CACNA1S phenotype

Supplement to: Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for the use of potent volatile anesthetic agents and succinylcholine in the context of RYR1 or CACNA1S genotypes

Tables and figures included in the supplement or referenced in the guideline^a:

Supplemental Table S1. Evidence linking RYR1 and CACNA1S genotype with malignant hyperthermia

RYR1 allele definition table

RYR1 allele functionality table

RYR1 frequency table

CACNA1S allele definition table

CACNA1S allele functionality table

CACNA1S frequency table

Gene resource mapping RYR1 gene resource mappings CACNA1S gene resource mappings

Drug resource mapping Desflurane Enflurane Halothane Isoflurane Methoxyflurane Sevoflurane Succinylcholine

Clinical decision support:b RYR1 consult text and implementation workflow CACNA1S consult text and implementation workflow Succinylcholine/volatile anesthetic pre- and post-test alerts and flow chart

^aSome of the tables included in the guideline may have been updated online, particularly to reflect newly described or newly characterized alleles. These include the gene-specific information tables (https://www.pharmgkb.org/page/pgxGeneRef) that support CPIC guidelines by providing information regarding star (*) allele definitions, allele function, allele frequency by major ethnic groups, translations of diplotype to phenotype, and gene resource mappings.

^bThese resources support the adoption of CPIC guidelines into the electronic health record with clinical decision support and provide information that clinical implementers find helpful.