Congenital myopathy

Gene: CASQ1

Red List (low evidence)

Comment on phenotypes: OMIM phenotype accessed 12th Nov 2025.

Created: 12 Nov 2025, 12:26 p.m. | Last Modified: 12 Nov 2025, 12:26 p.m.

Panel Version: 6.39

As reviewed previously, individuals affected by CASQ-1 related myopathy experience adult-onset symptoms. Therefore, this gene is not in scope for the Congenital myopathy panel.

Created: 12 Nov 2025, 12:25 p.m. | Last Modified: 12 Nov 2025, 12:25 p.m.

Panel Version: 6.38

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Myopathy, vacuolar, with CASQ1 aggregates, OMIM:616231

Publications

• 30258016

The rating of this gene has been updated from Amber to Red following NHS Genomic Medicine Service approval.

Created: 29 Jul 2022, 1:47 p.m. | Last Modified: 29 Jul 2022, 1:47 p.m.

Panel Version: 2.88

Red List (low evidence)

OMIM notes adult onset

PMID: 30258016 - 22 patients (12 families) where 21/22 carried a founder mutation p.Asp244Gly.
- Patients presented with adult onset proximal weakness, quadricep atrophy and 3/22 with cardiac involvement.
- Some patients were asymptomatic and diagnosed by elevated creatine kinase.
- Youngest age at onset was 12 years old, but only 2/22 were symptomatic <30 years of age.

PMID: 25116801 - 8 patients (4 families) with mild myopathy. All patients were heterozygous for the founder mutation p.Asp244Gly. Patients were aged 23-58 years old at the time of analysis, none mentioned to have childhood onset.

PMID: 26136523 - functionally shows that missense cause both wildtype and mutation protein to aggregate and mislocalise -> evidence of dominant negative mechanism. Lack of NMD predicted variants supports this finding.

Summary: Rare reports of childhood onset, none congenital

Created: 15 Jun 2020, 8:40 a.m. | Last Modified: 15 Jun 2020, 8:40 a.m.

Panel Version: 2.5

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Myopathy, vacuolar, with CASQ1 aggregates 616231

Publications

• 30258016
• 25116801
• 26136523

I don't know

Gene rating and review submitted by Rachael Mein, Viapath Guy's Hospital February 2019 on on behalf of London South GLH for the GMS Neurology specialist test group.

Created: 30 Apr 2019, 10:09 a.m.

I don't know

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Myopathy, vacuolar, with CASQ1 aggregates 616231

Publications

• 25116801

Variants in this GENE are reported as part of current diagnostic practice

Comment when marking as ready: Adult affected with mild myopathy and therefore phenotype not appropriate for inclusion on this panel based upon the current evidence.

Created: 7 Mar 2017, 4:27 p.m.

Comment on list classification: Associated with the phenotype but age of onset well into adulthood in most cases found. Therefore not considered appropriate.

Created: 7 Mar 2017, 4:26 p.m.

Green List (high evidence)

Calsequestrin (CASQ) is the main Ca2+ buffer in the terminal cisternae, part of the so called Triad. Other forms of congenital myopathies are caused by genetic defects in components of the triad such as RYR1, ORAI1, STIM1 and now also CASQ1. patients with CASQ1 pathogenic variants usually present with high CK levels, mild proximal weakness, and myalgia. variable age at onset, mostly in adult life. muscle biopsy findings were typically myopathic with vacuolar inclusions strongly react with antibodies against SR calcium–machinery proteins and also tubular aggregates. These features are in part similar and overlapping what seen in association with other diseases associated with the triad.

Created: 19 Sep 2025, 10:40 a.m. | Last Modified: 19 Sep 2025, 10:40 a.m.

Panel Version: 6.35

Calsequestrin (CASQ) is the main Ca2+ buffer in the terminal cisternae, part of the so called Triad. Other forms of congenital myopathies are caused by genetic defects in components of the triad such as RYR1, ORAI1, STIM1 and now also CASQ1. patients with CASQ1 pathogenic variants usually present with high CK levels, mild proximal weakness, and myalgia. variable age at onset, mostly in adult life. muscle biopsy findings were typically myopathic with vacuolar inclusions strongly react with antibodies against SR calcium–machinery proteins and also tubular aggregates. These features are in part similar and overlapping what seen in association with other diseases associated with the triad.

Created: 19 Sep 2025, 10:40 a.m. | Last Modified: 19 Sep 2025, 10:40 a.m.

Panel Version: 6.35

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Vacuolar myopathy with CASQ1 aggregates (VMCQA)

Publications

• PMID: 30258016