Rhabdomyolysis and metabolic muscle disorders
Gene: OBSCN
Comment on list classification: As recommended by Natalie Bibb and Andrew Swale, this gene is proposed for promotion to green as it is already green on the acute rhabdomyolysis panel (R419, https://panelapp.genomicsengland.co.uk/panels/1141/) based on recommendation by the NHS Genomic Medicine Service.Created: 23 Aug 2023, 12:40 p.m. | Last Modified: 23 Aug 2023, 12:40 p.m.
Panel Version: 3.18
Six unrelated individuals with biallelic loss of function variants (2 homozygous and 4 heterozygous cases with 10 different variants) in OBSCN gene presented with severe recurrent rhabdomyolysis between 12 and 27 years of age. The triggers for rhabdomyolysis in 2 cases were heat and exercise, in 2 only exercise, in 1 following long travel periods, and in 1 the episodes occurred spontaneously.
This gene has already been rated green in the 'Rhabdomyolysis and Metabolic Myopathy' panel in PanelApp Australia (https://panelapp.agha.umccr.org/panels/3084/gene/OBSCN/) and been associated with relevant phenotype in OMIM (MIM #620235).Created: 23 Aug 2023, 12:37 p.m. | Last Modified: 23 Aug 2023, 12:37 p.m.
Panel Version: 3.14
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
{Rhabdomyolysis, susceptibility to, 1}, OMIM:620235
Publications
The rating of this gene has been updated to green and the mode of inheritance set to "BIALLELIC, autosomal or pseudoautosomal" following NHS Genomic Medicine Service approval.Created: 11 Oct 2023, 11:17 a.m. | Last Modified: 11 Oct 2023, 11:42 a.m.
Panel Version: 3.37
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: 1.46
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Comment when marking as ready: Not associated with phenotype in OMIM or G2P. No variants reported to date, however, expert reviewer quoted unpublished observations and so this gene has now been tagged with the "watchlist" tagCreated: 4 Jan 2017, 1:23 p.m.
Tag Q3_23_promote_green was removed from gene: OBSCN. Tag Q3_23_NHS_review was removed from gene: OBSCN.
Source Expert Review Green was added to OBSCN. Source NHS GMS was added to OBSCN. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Phenotypes for gene: OBSCN were changed from {Rhabdomyolysis, susceptibility to, 1}, OMIM:620235 to {Rhabdomyolysis, susceptibility to, 1}, OMIM:620235
Phenotypes for gene: OBSCN were changed from to {Rhabdomyolysis, susceptibility to, 1}, OMIM:620235
Tag watchlist was removed from gene: OBSCN. Tag Q3_23_promote_green tag was added to gene: OBSCN. Tag Q3_23_NHS_review tag was added to gene: OBSCN.
Gene: obscn has been classified as Amber List (Moderate Evidence).
Gene: obscn has been classified as Amber List (Moderate Evidence).
Mode of inheritance for gene: OBSCN was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mode of inheritance for gene: OBSCN was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Mode of inheritance for gene: OBSCN was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OBSCN were set to 18477606
Panel promoted to V1 4th January 2017
This gene has been classified as Red List (Low Evidence).
This gene has been classified as Red List (Low Evidence).
Publications for OBSCN were set to 18477606
Mode of inheritance for OBSCN was changed to Unknown
This gene has been classified as Red List (Low Evidence).
OBSCN was created by Ros Quinlivan
OBSCN was added to Rhabdomyolysis and metabolic muscle disorderspanel. Sources: Expert Review