Undiagnosed metabolic disorders
Gene: SLC6A19EnsemblGeneIds (GRCh38): ENSG00000174358
EnsemblGeneIds (GRCh37): ENSG00000174358
OMIM: 608893, Gene2Phenotype
SLC6A19 is in 7 panels
3 reviews
Achchuthan Shanmugasundram (Genomics England Curator)
Comment on mode of inheritance: As reviewed by Tracy Lester, SLC6A19 is associated with Hartnup disorder (MIM #234500), which is caused by biallelic variants. SLC6A19 is currently associated with Hyperglycinuria (MIM #138500) and Iminoglycinuria (MIM #242600) in both PanelApp and PanelApp Australia and hence the MOI was set to both monoallelic and biallelic. However, these phenotypes are caused by SLC36A2.
The association in PanelApp was due to the speculation in PMID:19033659 that combination of variants in SLC36A2 with variants in SLC6A20 or SLC6A19 may have contributed to these phenotypes in three of the reported families. The identified variant from SLC6A19 has now been classified as polymorphism because it was present in 62,195 of 282,492 alleles and in 7,227 homozygotes in the gnomAD database (v2.1.1), for an allele frequency of 0.2202 (https://www.omim.org/entry/608893?search=slc6a19&highlight=slc6a19#allelicVariants)
Hence, the MOI should be updated to 'BIALLELIC, autosomal or pseudoautosomal' in this panel.Created: 11 Jun 2024, 5:04 p.m. | Last Modified: 11 Jun 2024, 5:15 p.m.
Panel Version: 1.619
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Hartnup disorder, OMIM:234500
Tracy Lester (Genetics laboratory, Oxford UK)
I am not sure why this gene has been added with monoallelic inheritance as an option as Hartnup is a recessive condition. Suggest inheritance is changed to biallelic onlyCreated: 20 Feb 2024, 10:14 a.m. | Last Modified: 20 Feb 2024, 10:14 a.m.
Panel Version: 1.613
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Variants in this GENE are reported as part of current diagnostic practice
Sarah Leigh (Genomics England Curator)
Comment when marking as ready: Associated with phenotypes in OMIM, not in G2P / DD. At least 6 variants reported in 8 cases of Hartnup disorder 234500Created: 19 Jan 2017, 11:16 a.m.
Details
- Mode of Inheritance
- BIALLELIC, autosomal or pseudoautosomal
- Sources
-
- Expert Review Green
- Radboud University Medical Center, Nijmegen
- UKGTN
- Literature
- Phenotypes
-
- Hartnup disorder, OMIM:234500
- OMIM
- 608893
- Clinvar variants
- Variants in SLC6A19
- Penetrance
- Complete
- Publications
- Panels with this gene
History Filter Activity
Set mode of inheritance
Achchuthan Shanmugasundram (Genomics England Curator)Mode of inheritance for gene: SLC6A19 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Removed Tag, Removed Tag
Achchuthan Shanmugasundram (Genomics England Curator)Tag Q2_24_MOI was removed from gene: SLC6A19. Tag Q2_24_expert_review was removed from gene: SLC6A19.
Removed Tag
Achchuthan Shanmugasundram (Genomics England Curator)Tag Q2_24_NHS_review was removed from gene: SLC6A19.
Added Tag, Added Tag
Achchuthan Shanmugasundram (Genomics England Curator)Tag Q2_24_expert_review tag was added to gene: SLC6A19. Tag Q2_24_NHS_review tag was added to gene: SLC6A19.
Added Tag
Achchuthan Shanmugasundram (Genomics England Curator)Tag Q2_24_MOI tag was added to gene: SLC6A19.
Set Phenotypes
Achchuthan Shanmugasundram (Genomics England Curator)Phenotypes for gene: SLC6A19 were changed from Hartnup disorder 234500 AR; Hyperglycinuria 138500 AD; Iminoglycinuria, digenic 242600 AR to Hartnup disorder, OMIM:234500
Set mode of inheritance
Achchuthan Shanmugasundram (Genomics England Curator)Mode of inheritance for gene: SLC6A19 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
panel promoted to version 1
Sarah Leigh (Genomics England Curator)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
Gene classified by Genomics England curator
Sarah Leigh (Genomics England Curator)This gene has been classified as Green List (High Evidence).
Set publications
Sarah Leigh (Genomics England Curator)Publications for SLC6A19 were set to 27604308; 20399395; 19335424
Set Phenotypes
Sarah Leigh (Genomics England Curator)Phenotypes for SLC6A19 were set to Hartnup disorder 234500 AR; Hyperglycinuria 138500 AD; Iminoglycinuria, digenic 242600 AR
Gene classified by Genomics England curator
Sarah Leigh (Genomics England Curator)This gene has been classified as Green List (High Evidence).
Upload gene information
Sarah Leigh (Genomics England Curator)SLC6A19 was added to Undiagnosed metabolic disorderspanel. Sources: UKGTN,Radboud University Medical Center, Nijmegen
Set Mode of Inheritance
Sarah Leigh (Genomics England Curator)Model of inheritance for gene SLC6A19 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Added New Source
Sarah Leigh (Genomics England Curator)SLC6A19 was added to Undiagnosed metabolic disorderspanel. Sources: Literature
Created
Sarah Leigh (Genomics England Curator)SLC6A19 was created by sleigh