Rhabdomyolysis and metabolic muscle disorders

Gene: OBSCN

Green List (high evidence)

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

• 34957489

Green List (high evidence)

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

• 33438037

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 No variants reported to date, however, expert reviewer quoted unpublished observations and so this gene has now been tagged with the "watchlist" tag

Created: 4 Jan 2017, 1:23 p.m.

Red List (low evidence)