Congenital myopathy

Gene: CACNA1H

Amber List (moderate evidence)

CACNA1H (calcium voltage-gated channel subunit alpha1 H)
EnsemblGeneIds (GRCh38): ENSG00000196557
EnsemblGeneIds (GRCh37): ENSG00000196557
OMIM: 607904, Gene2Phenotype
CACNA1H is in 5 panels

2 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

I don't know

Comment on list classification: Although there are three unrelated individuals reported with biallelic CACNA1H variants so far, only one of them was reported with congenital amyotrophy/ myopathy. There is also functional evidence available in support of the association. Hence, this gene can only be rated amber with current evidence on this panel.
Created: 27 May 2026, 6:53 p.m. | Last Modified: 27 May 2026, 6:53 p.m.
Panel Version: 7.28
PMID:25773295 (2015) reported exome sequencing of 44 amyotrophic lateral sclerosis (ALS) proband-unaffected parents trios, of which one patient (Trio #14) was identified with two compound heterozygous missense variants in CACNA1H gene (p. Val1683Met
and p.Ala1699Thr).

PMID:31070086 (2019) reported a 13-month-old girl with severe infantile-onset amyotrophy in whom two compound heterozygous variants in the gene CACNA1H were identified (p.Val681Leu and p.Asp1233His). Patch-clamp electrophysiology of the individual variants and co-expression showed alterations of Cav3.2 gating properties collectively consistent with a loss-of-channel function.

PMID:41272325 (2026) reported a 4-year-old boy diagnosed with epilepsy with myoclonic-atonic seizures, and identified with two missense variants in CACNA1H. One was a novel variant, p.Asp949His, while the other was a known variant, p.Arg788Cys (previously reported in heterozygous state in patients from PMID:1289167).

Biallelic variants in CACNA1H are not yet associated with relevant phenotypes either in OMIM, ClinGen, Gene2Phenotype or PanelApp Australia.
Created: 27 May 2026, 6:34 p.m. | Last Modified: 27 May 2026, 6:34 p.m.
Panel Version: 7.25

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Anna Sarkozy (Great Ormond Street Hospital)

Green List (high evidence)

mutations identified in rare cases of severe congenital amyoplasia/myopathy. This condition presents with severe early-onset muscle weakness and atrophy, representing a potential novel form of congenital myopathy linked to channel loss-of-function.
Created: 22 May 2026, 1:49 p.m. | Last Modified: 22 May 2026, 1:49 p.m.
Panel Version: 7.14

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • NHS GMS
OMIM
607904
Clinvar variants
Variants in CACNA1H
Penetrance
None
Publications
Panels with this gene

History Filter Activity

27 May 2026, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: cacna1h has been classified as Amber List (Moderate Evidence).

27 May 2026, Gel status: 0

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: CACNA1H were set to

27 May 2026, Gel status: 0

Set mode of inheritance

Achchuthan Shanmugasundram (Genomics England Curator)

Mode of inheritance for gene: CACNA1H was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal

22 May 2026, Gel status: 0

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: cacna1h has been removed from the panel.

22 May 2026, Gel status: 1

Created, Added New Source, Set mode of inheritance

Arina Puzriakova (Genomics England Curator)

gene: CACNA1H was added gene: CACNA1H was added to Congenital myopathy. Sources: NHS GMS Mode of inheritance for gene: CACNA1H was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown