CACNA1S: a malignant hyperthermia gene that cannot clear you
Malignant hyperthermia is a reaction to general anaesthesia that goes from normal to life-threatening in minutes. CACNA1S is one of two genes with published anaesthetic guidance attached to it, and it is the smaller of the two by a wide margin. That asymmetry is the most important thing on this page.
Also known as: Cav1.1, calcium voltage-gated channel subunit alpha1 S.
What CACNA1S does
The gene makes part of a calcium channel in skeletal muscle, the switch that converts a nerve signal into a muscle contraction. Certain variants leave that switch prone to opening when it should not. Under a halogenated anaesthetic gas or the muscle relaxant succinylcholine, calcium floods out of storage and stays out, muscle burns fuel continuously, body temperature climbs and the muscle itself starts to break down. Treatment exists and works when the reaction is caught, which is why anaesthetic teams watch for it.
The susceptibility groups
There are only two categories here, and neither is a metabolizer rate. Malignant hyperthermia susceptibility means a variant with established evidence for the trait is present. Uncertain susceptibility means no such variant was found, which is a much weaker statement than it sounds. CPIC's own wording is explicit that a result in this category does not eliminate the chance of susceptibility, because the genetic cause of roughly half of confirmed malignant hyperthermia cases is still unknown.
Medications where it matters
succinylcholine (suxamethonium)
Succinylcholine is a fast, short-acting muscle relaxant used to secure an airway quickly, which puts it in emergency and rapid-sequence settings where there is no time to look anything up. It is one of the two trigger classes named in the guidance, and the recommendation below treats it as relatively contraindicated in a susceptible person.
| If your result is | Published CPIC guidance |
|---|---|
| Malignant Hyperthermia Susceptibility | Per CPIC (A): "Halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS." |
| Uncertain Susceptibility | Per CPIC (A): "Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants." |
sevoflurane
Sevoflurane is a common inhaled anaesthetic and stands here for the whole halogenated volatile class, which also includes desflurane, isoflurane, halothane, enflurane and methoxyflurane. CPIC publishes the same recommendation for every agent in that class, so the table below stands for all of them.
| If your result is | Published CPIC guidance |
|---|---|
| Malignant Hyperthermia Susceptibility | Per CPIC (A): "Halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS." |
| Uncertain Susceptibility | Per CPIC (A): "Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants." |
isoflurane
Included so the pattern is visible rather than assumed: the recommendation does not soften from one halogenated agent to the next. If a susceptible result is present, the class is avoided, and alternative anaesthetic techniques are widely available.
| If your result is | Published CPIC guidance |
|---|---|
| Malignant Hyperthermia Susceptibility | Per CPIC (A): "Halogenated volatile anesthetics or the depolarizing muscle relaxant succinylcholine are relatively contraindicated in persons with malignant hyperthermia susceptibility (MHS). They should not be used, except in extraordinary circumstances where the benefits outweigh the risks. In general, alternative anesthetics are widely available and effective in patients with MHS." |
| Uncertain Susceptibility | Per CPIC (A): "Clinical findings, family history, further genetic testing and other laboratory data should guide use of halogenated volatile anesthetics or depolarizing muscle relaxants." |
Is this in your raw DNA file?
Two limits matter more here than the usual chip-versus-sequence question. The first is that CACNA1S is a Deep Read gene, read from aligned reads in a BAM or CRAM file, not from a consumer chip export. The second is larger: most inherited malignant hyperthermia susceptibility traces to RYR1, a different gene, and RYR1 is not in the Aimosti panel. So a CACNA1S result that finds nothing has not screened you for malignant hyperthermia. It has checked a minority of the known genetic causes and come back empty. If you have a personal or family history of a bad reaction to anaesthesia, the path is a specialist malignant hyperthermia centre, which uses family history, muscle contracture testing and targeted genetic testing together. This page is not that.
A genotyping chip reads only a few hundred thousand pre-selected positions, about 0.02% of your genome, chosen for common variation. It does not sequence the rest, so it cannot find the rare or novel pathogenic variants the clinical and carrier modules look for: a “no finding” from chip data means “this chip never looked”, far more so than with whole-genome sequencing. Chip data suits common-variant traits, pharmacogenomic tag SNPs, and haplogroup ancestry, not clinical or carrier screening.
Common questions
My CACNA1S result found nothing. Am I safe under anaesthesia?
No, and this is the single point worth taking from the page. Uncertain susceptibility means no known CACNA1S variant was found. Most malignant hyperthermia susceptibility comes from RYR1, which Aimosti does not read, and about half of confirmed cases have no identified genetic cause at all. A clear result here rules out very little.
Someone in my family had a malignant hyperthermia reaction. What should I do?
Tell every anaesthetist you meet, and ask to be referred to a malignant hyperthermia service. They will work from the affected relative's diagnosis, which is the most informative starting point available, and can arrange contracture testing or targeted genetic testing. Consumer genome re-analysis is not a step on that path.
Why does Aimosti report CACNA1S but not RYR1?
Because RYR1 is a large gene where most reported variants are of uncertain significance, and calling it responsibly means a curated clinical interpretation rather than a variant list. CACNA1S has a short, well-characterised set of variants that CPIC grades, which is the standard the Deep Read panel holds to. Reporting the smaller gene without claiming it covers the larger one is the honest version of that trade.
Should a susceptible result go on a medical record?
That is a conversation to have with a clinician rather than a step to take from a report. A result read from your own file is not a clinical diagnosis, and a malignant hyperthermia service is the body that can confirm one and record it properly. What you can do immediately is mention it before any procedure involving general anaesthesia.