Rhabdomyolysis and Metabolic Myopathy

Gene: CASQ1

Green List (high evidence)

CASQ1 (calsequestrin 1)
EnsemblGeneIds (GRCh38): ENSG00000143318
EnsemblGeneIds (GRCh37): ENSG00000143318
OMIM: 114250, Gene2Phenotype
CASQ1 is in 5 panels

3 reviews

Ain Roesley (Victorian Clinical Genetics Services)

Green List (high evidence)

Established association.

p.Asp244Gly is a founder variant
Created: 4 Apr 2022, 12:52 a.m. | Last Modified: 4 Apr 2022, 12:52 a.m.
Panel Version: 0.12498

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Myopathy, vacuolar, with CASQ1 aggregates MIM#616231

Publications

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

Elena Savva (Victorian Clinical Genetics Services)

I don't know

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, mostly adult
Sources: Expert list
Created: 15 Jun 2020, 4:06 a.m.

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

Phenotypes
Myopathy, vacuolar, with CASQ1 aggregates 616231

Publications

Mode of pathogenicity
Other

Bryony Thompson (Royal Melbourne Hospital)

Green List (high evidence)

Exercise intolerance has been reported as the presenting symptom in at least 5 cases, mainly with the described founder mutation (p.Asp244Gly).
Sources: Literature
Created: 29 May 2020, 3:14 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Myopathy, vacuolar, with CASQ1 aggregates MIM#616231

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Expert list
  • Expert Review Green
  • Literature
Phenotypes
  • Myopathy, vacuolar, with CASQ1 aggregates MIM#616231
OMIM
114250
Clinvar variants
Variants in CASQ1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

29 May 2020, Gel status: 3

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: casq1 has been classified as Green List (High Evidence).

29 May 2020, Gel status: 3

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: casq1 has been classified as Green List (High Evidence).

29 May 2020, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Bryony Thompson (Royal Melbourne Hospital)

gene: CASQ1 was added gene: CASQ1 was added to Rhabdomyolysis RMH. Sources: Literature Mode of inheritance for gene: CASQ1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CASQ1 were set to 30258016 Phenotypes for gene: CASQ1 were set to Myopathy, vacuolar, with CASQ1 aggregates MIM#616231 Review for gene: CASQ1 was set to GREEN