Undiagnosed metabolic disordersGene: ISCU
Comment on mode of inheritance: PMID 29079705 reports a novel de novo dominant variant missense p.G97V variant has been reported and therefore this may represent a specific mechanism of action. Further evidence is needed to determine which (if any) other monoallelic variants will cause disease beyond mitochondrial myopathy, which justifies the mode of inheritance recorded.
Created: 23 Jun 2020, 2:06 p.m. | Last Modified: 23 Jun 2020, 2:10 p.m.
Panel Version: 1.415
Comment on list classification: Sufficient published reported biallelic cases, with supportive functional studies. The most frequent reported variant c.343+382G>C g.108567650G>C is deep in intron five of the gene and strengthens a weak splicing acceptor site, with consequent retention of a 100-bp intronic sequence upstream of the known terminal exon, introduction of a stop codon and decreased levels of ISCU mRNA and protein (PMID 18304497). This may be missed by standard sequencing.
Created: 15 Aug 2019, 12:20 p.m. | Last Modified: 15 Aug 2019, 12:20 p.m.
Panel Version: 1.167
Amber review assigned as this gene is Green on the V1 panel(s) named as a phenotype(s)
Created: 6 Jan 2017, 1:59 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Rhabdomyolysis and metabolic muscle disorders
Mode of inheritance for gene: ISCU was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Gene: iscu has been classified as Green List (High Evidence).
Tag non-coding-known-pathogenic tag was added to gene: ISCU.
Publications for gene: ISCU were set to 27604308
Construction of “Undiagnosed Metabolic Disorders” (UDM) panel • The 614 genes from the neurometabolic gene panel (PMID: 27604308) added • Green genes downloaded from V1 metabolic panels (Cerebral folate deficiency, Congenital disorders of glycosylation, Hyperammonaemia, Ketotic hypoglycaemia, Mitochondrial disorders, Mucopolysaccharideosis, Gaucher, Fabry, Peroxisomal disorders), sources replaced with "Expert review green", then loaded as a review onto UDM panel, resulting in 367 green genes and 333 red (therefore 86 new green genes included from the additional metabolic panels that weren't previously on the UDM panel) • Downloaded green genes from all panels. Removed genes from none V1 panels. Removed genes from the metabolic panels mentioned above. Compared the remaining genes with the red genes from UDM panel. Loaded as an "Expert review Amber" review to the overlapping genes, (the panel name where the genes came from was used as the phenotype) • Used variant information from PMID 27604308 to review the genes on this panel • Reviewed genes on UDM panel with genes from Emory "Inherited Metabolic Disorders: Sequencing Panel" and UKGTN “Inborn Errors of Metabolism 226 panel”, changing status where appropriate, added 14 UKGTN genes that had not be listed before • Review 10 red genes that had not previously been reviewed, 4/10 were reclassified as green • Review the remaining 145 red genes that had not previously been reviewed (shared between reviewers EM, RF, LD, AT, HB, ON & SL), resulting in 60 green, 11 amber, 70 red, 4 I don’t know reviews) • Reviewed genes from PMID: 24816252 as a publication to genes found in the Inborn error or metabolism Genes metabolomics GWAS paper (figure 5). 2 new genes added
ISCU was added to Undiagnosed metabolic disorderspanel. Source: Expert Review Amber Model of inheritance for gene ISCU was set to BIALLELIC, autosomal or pseudoautosomal
ISCU was added to Undiagnosed metabolic disorderspanel. Sources: Literature
ISCU was created by sleigh