Myopathy: genes and variants
Myopathy is linked to 9 analyzed proteins (CACNA1S, COL6A2, SELENON, RYR3, MYH7, FHL1, FLNC, RYR1 and 1 more). 5 DNA variants are known to cause it; 207 more are uncertain, and 1 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: congenital myopathy; congenital myopathy 18; congenital myopathy 20; Congenital myopathy 4A, autosomal dominant
Genes linked to Myopathy
CACNA1S: Voltage-dependent L-type calcium channel subunit alpha-1S
Its voltage sensing in skeletal-muscle transverse tubules mechanically activates RYR1 and couples membrane depolarization to sarcoplasmic-reticulum calcium release. Pathogenic variants can cause hypokalemic periodic paralysis, malignant-hyperthermia susceptibility, and congenital myopathy.
3 disease-causing and 181 uncertain variants in CACNA1S are linked to Myopathy.
COL6A2: Collagen alpha-2(VI) chain
It assembles with other collagen VI chains into extracellular microfibrils that support muscle and connective-tissue integrity. Dominant or recessive pathogenic variants cause collagen VI-related muscular dystrophy and myopathy across a broad severity spectrum.
1 disease-causing and 0 uncertain variants in COL6A2 are linked to Myopathy.
SELENON: Selenoprotein N
It helps maintain redox and calcium homeostasis within the endoplasmic reticulum of skeletal muscle, particularly during oxidative and mechanical stress. Biallelic loss-of-function variants cause SELENON-related myopathy, often with axial weakness, rigid spine, and disproportionate respiratory impairment.
1 disease-causing and 0 uncertain variants in SELENON are linked to Myopathy.
RYR3: Ryanodine receptor 3
An intracellular calcium-release channel that opens in response to calcium and releases more calcium from the endoplasmic or sarcoplasmic reticulum. This calcium-induced calcium release contributes to muscle contraction and broader calcium signaling in non-muscle cells.
0 disease-causing and 21 uncertain variants in RYR3 are linked to Myopathy.
MYH7: Myosin-7
Its beta-myosin motor converts ATP hydrolysis into force within cardiac and slow-skeletal-muscle sarcomeres. Pathogenic variants are major causes of hypertrophic and dilated cardiomyopathy and can also produce inherited skeletal myopathies.
0 disease-causing and 1 uncertain variants in MYH7 are linked to Myopathy.
FHL1: Four and a half LIM domains protein 1
It organizes protein complexes in striated muscle and participates in mechanosensing, sarcomere structure, and transcriptional responses. X-linked pathogenic variants cause a spectrum including reducing-body myopathy, Emery-Dreifuss muscular dystrophy, scapuloperoneal myopathy, and cardiomyopathy.
0 disease-causing and 0 uncertain variants in FHL1 are linked to Myopathy.
FLNC: Filamin-C
It crosslinks actin and anchors signaling and structural proteins at Z-discs, costameres, and other mechanically stressed sites in striated muscle. Pathogenic variants can cause arrhythmogenic or dilated cardiomyopathy as well as myofibrillar and distal myopathies.
0 disease-causing and 0 uncertain variants in FLNC are linked to Myopathy.
RYR1: Ryanodine receptor 1
It releases calcium from the skeletal-muscle sarcoplasmic reticulum when Cav1.1 senses membrane depolarization, directly coupling excitation to contraction. Pathogenic variants cause malignant-hyperthermia susceptibility and a broad spectrum of congenital RYR1-related myopathies.
0 disease-causing and 0 uncertain variants in RYR1 are linked to Myopathy.
TTN: Titin
Its enormous titin polypeptide spans much of the sarcomere and provides passive elasticity, structural alignment, and mechanosensing in striated muscle. Truncating variants are among the most common genetic causes of dilated cardiomyopathy, while other variants cause diverse skeletal and cardiac myopathies.
0 disease-causing and 0 uncertain variants in TTN are linked to Myopathy.
Weakly linked (only a few uncertain records): ETFDH, NEB and OCRL.
Known disease-causing variants in Myopathy
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| CACNA1S R528H | 528 | II | Disease-causing (★★) |
| CACNA1S R1086S | 1086 | Cytoplasmic | Disease-causing (★★) |
| SELENON G315S | 315 | Disease-causing (★★) | |
| CACNA1S P742S | 742 | Cytoplasmic | Disease-causing (★★) |
| COL6A2 G298R | 298 | Triple-helical region | Disease-causing (★) |
Uncertain variants in Myopathy that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| CACNA1S R1086C | 1086 | Cytoplasmic | Conflicting reports (★) | +6: R1086S at the same position is pathogenic; REVEL 0.956 |
Same protein, different disease
- Hypokalemic periodic paralysis is also caused by CACNA1S variants; they fall mostly in different places as the Myopathy variants (14 disease-causing).
- Bethlem myopathy is also caused by COL6A2 variants; they fall mostly in different places as the Myopathy variants (39 disease-causing).
- Ullrich congenital muscular dystrophy is also caused by COL6A2 variants; they fall mostly in different places as the Myopathy variants (8 disease-causing).
- Eichsfeld type congenital muscular dystrophy is also caused by SELENON variants; they fall mostly in different places as the Myopathy variants (7 disease-causing).
Diseases related to Myopathy
- Hypertrophic cardiomyopathy, also linked to FLNC, MYH7 and TTN
- Dilated cardiomyopathy, also linked to FLNC, MYH7 and TTN
- Muscular dystrophy, also linked to COL6A2 and SELENON
- Restrictive cardiomyopathy, also linked to FLNC and MYH7
- Centronuclear myopathy, also linked to FHL1 and RYR1
- Familial isolated dilated cardiomyopathy, also linked to MYH7 and TTN
- Bethlem myopathy, also linked to COL6A2
- Cardiac arrhythmia, also linked to TTN
- Autosomal recessive limb-girdle muscular dystrophy, also linked to TTN
- Primary dilated cardiomyopathy, also linked to MYH7
- Hypokalemic periodic paralysis, also linked to CACNA1S
- Skeletal muscle channelopathy, also linked to CACNA1S
Frequently asked questions
Which genes are linked to Myopathy?
In CATVariant, Myopathy is linked to 9 analyzed proteins: CACNA1S (Voltage-dependent L-type calcium channel subunit alpha-1S), COL6A2 (Collagen alpha-2(VI) chain), SELENON (Selenoprotein N), RYR3 (Ryanodine receptor 3), MYH7 (Myosin-7), FHL1 (Four and a half LIM domains protein 1) and 3 more.
How many genetic variants are linked to Myopathy?
246 variants: 5 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 207 are of uncertain significance or have conflicting reports.
Which uncertain variants in Myopathy look disease-causing?
1 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example CACNA1S R1086C. These are leads for expert review, not diagnoses.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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