Rhabdomyolysis and Metabolic Myopathy

Gene: OBSCN

Green List (high evidence)

OBSCN (obscurin, cytoskeletal calmodulin and titin-interacting RhoGEF)
EnsemblGeneIds (GRCh38): ENSG00000154358
EnsemblGeneIds (GRCh37): ENSG00000154358
OMIM: 608616, Gene2Phenotype
OBSCN is in 3 panels

3 reviews

Ee Ming Wong (Victorian Clinical Genetics Services)

Green List (high evidence)

-Six unrelated individuals with severe, recurrent rhabdomyolysis carrying bi-allelic loss of function variants
-Three of six probands experienced acute renal failure
-None presented with cardiac involvement/symptoms of cardiac disease
-Patient muscles demonstrated reduced OBSCN expression and loss of obscurin protein
Sources: Literature
Created: 1 Feb 2022, 11:33 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Rhabdomyolysis, MONDO:0005290

Publications

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

Eleanor Williams (Genomics England)

Red List (low evidence)

Additional evidence to question the pathogenicity of reported variants:
PMID: 33438037 - Fukuzawa et al 2021 - look at protein–protein interactions and protein domain stability, using quantitative biochemical and biophysical approaches on the proposed pathogenic R4344Q variant which is found in 15% of African Americans, along with the previously reported R4444W variant. They find no evidence for a pathogenetic effect.
Created: 6 Jul 2021, 12:08 p.m. | Last Modified: 6 Jul 2021, 12:08 p.m.
Panel Version: 0.8229

Publications

Paul De Fazio (Victorian Clinical Genetics Services)

Red List (low evidence)

Limited evidence by ClinGen working group.

Via ClinGen: 8 probands in 3 publications but only 3 probands from 1 publication were though to have pathogenic variants (others were excluded based on population frequency and expert review).

No additional case reports were found. A mouse model lends some support to the association of this gene with heart disease although not HCM specifically.
Sources: Literature
Created: 29 Jul 2020, 6:33 a.m.

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

Phenotypes
Hypertrophic cardiomyopathy

Publications

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
Phenotypes
  • Rhabdomyolysis, MONDO:0005290, OBSCN-related
OMIM
608616
Clinvar variants
Variants in OBSCN
Penetrance
unknown
Publications
Panels with this gene

History Filter Activity

1 Feb 2022, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: OBSCN were changed from Rhabdomyolysis, MONDO:0005290 to Rhabdomyolysis, MONDO:0005290, OBSCN-related

1 Feb 2022, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

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

1 Feb 2022, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

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

1 Feb 2022, Gel status: 0

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

Ee Ming Wong (Victorian Clinical Genetics Services)

gene: OBSCN was added gene: OBSCN was added to Rhabdomyolysis. Sources: Literature Mode of inheritance for gene: OBSCN was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: OBSCN were set to PMID: 34957489 Phenotypes for gene: OBSCN were set to Rhabdomyolysis, MONDO:0005290 Penetrance for gene: OBSCN were set to unknown Review for gene: OBSCN was set to GREEN gene: OBSCN was marked as current diagnostic