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Likely inborn error of metabolism - targeted testing not possible v2.257 | GLS_GCA | Eleanor Williams Tag for-review was removed from STR: GLS_GCA. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v2.223 | GLS | Sarah Leigh Tag for-review was removed from gene: GLS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v2.223 | GLS | Sarah Leigh commented on gene: GLS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v2.196 | GLS_GCA | Arina Puzriakova Phenotypes for STR: GLS_GCA were changed from Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733 to Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v2.195 | GLS | Arina Puzriakova edited their review of gene: GLS: Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v2.195 | GLS | Arina Puzriakova commented on gene: GLS: Added 'watchlist_MOI' tag to highlight monoallelic phenotype (MIM# 618339) which is also relevant to this panel, but as there is only a single case reported to date this is not yet sufficient to update the MOI. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v2.195 | GLS | Arina Puzriakova Phenotypes for gene: GLS were changed from Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733; Developmental and epileptic encephalopathy 71, OMIM:618328; Developmental and epileptic encephalopathy, 71, MONDO:0032678; ?Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, OMIM:618339; Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, MONDO:0032685 to Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Developmental and epileptic encephalopathy 71, OMIM:618328; ?Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, OMIM:618339 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v2.194 | GLS | Arina Puzriakova Tag watchlist_moi tag was added to gene: GLS. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v2.50 | GLS_GCA | Arina Puzriakova Classified STR: GLS_GCA as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v2.50 | GLS_GCA | Arina Puzriakova Str: gls_gca has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v2.49 | GLS_GCA |
Arina Puzriakova STR: GLS_GCA was added STR: GLS_GCA was added to Inborn errors of metabolism. Sources: Literature STR, NGS Not Validated, for-review tags were added to STR: GLS_GCA. Mode of inheritance for STR: GLS_GCA was set to BIALLELIC, autosomal or pseudoautosomal Publications for STR: GLS_GCA were set to 30970188 Phenotypes for STR: GLS_GCA were set to Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733 Review for STR: GLS_GCA was set to GREEN Added comment: GLS is associated with relevant phenotypes in OMIM, but currently is not in Gene2Phenoype. ---------- - PMID: 30970188 (2019) - Three unrelated cases who presented with an early-onset global developmental delay, progressive ataxia, and elevated levels of glutamine (MIM# 618412). One patient also showed cerebellar atrophy. All 3 individuals harboured a large trinucleotide (GCA) repeat expansion in the 5' UTR (length: 680-1,500-copy repeats). The repeat expansion was found in homozygosity in 1 case, and occurred in compound heterozygosity with an SNV in the other two cases (missense and frameshift variant, respectively). Functional analysis showed the repeat expansion results in reduced expression and glutaminase deficiency. Sources: Literature |
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Likely inborn error of metabolism - targeted testing not possible v2.48 | GLS | Arina Puzriakova Classified gene: GLS as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v2.48 | GLS |
Arina Puzriakova Added comment: Comment on list classification: There are sufficient cases, supported by functional data, to rate this gene Green - however, detection of the 5' UTR triplet expansion (PMID:30970188) has not yet been validated within the Genomics England pipeline. When excluding cases with the STR, the remaining evidence is not sufficient for inclusion as diagnostic-grade and therefore this gene is tagged 'for-review' to assess whether it should be downgraded to Amber until the STR is validated or additional cases arise. |
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Likely inborn error of metabolism - targeted testing not possible v2.48 | GLS | Arina Puzriakova Gene: gls has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v2.47 | GLS | Arina Puzriakova Phenotypes for gene: GLS were changed from Glucosidase 1 deficiency (Disorders of protein N-glycosylation); Epileptic encephalopathy, early infantile, 71 618328; Global developmental delay, progressive ataxia, and elevated glutamine 618412 to Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733; Developmental and epileptic encephalopathy 71, OMIM:618328; Developmental and epileptic encephalopathy, 71, MONDO:0032678; ?Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, OMIM:618339; Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, MONDO:0032685 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v2.46 | GLS | Arina Puzriakova Publications for gene: GLS were set to 27604308; 30575854; 29468182 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v2.45 | GLS | Arina Puzriakova Added comment: Comment on mode of inheritance: As evidence for pathogenicity of monoallelic variants is limited (currently only 1 case), MOI will remain as 'Biallelic' until further cases emerge that support an association between monoallelic variants and disease. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v2.45 | GLS | Arina Puzriakova Mode of inheritance for gene: GLS was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v2.44 | GLS |
Arina Puzriakova Tag STR tag was added to gene: GLS. Tag for-review tag was added to gene: GLS. |
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Likely inborn error of metabolism - targeted testing not possible v2.44 | GLS | Arina Puzriakova reviewed gene: GLS: Rating: ; Mode of pathogenicity: None; Publications: 30970188, 30575854, 30239721; Phenotypes: Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412, Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733, Developmental and epileptic encephalopathy 71, OMIM:618328, Developmental and epileptic encephalopathy, 71, MONDO:0032678, ?Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, OMIM:618339, Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, MONDO:0032685; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v1.414 | GLS | Ellen McDonagh edited their review of gene: GLS: Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v1.414 | GLS | Ellen McDonagh changed review comment from: Comment on phenotypes: This gene now appears in OMIm with a disease due to new publications.; to: Comment on phenotypes: This gene now appears in OMIM with a disease due to new publications. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v1.414 | GLS | Ellen McDonagh Added comment: Comment on phenotypes: This gene now appears in OMIm with a disease due to new publications. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v1.414 | GLS | Ellen McDonagh Phenotypes for gene: GLS were changed from Glucosidase 1 deficiency (Disorders of protein N-glycosylation) to Glucosidase 1 deficiency (Disorders of protein N-glycosylation); Epileptic encephalopathy, early infantile, 71 618328; Global developmental delay, progressive ataxia, and elevated glutamine 618412 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v1.413 | GLS | Ellen McDonagh Classified gene: GLS as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v1.413 | GLS | Ellen McDonagh Added comment: Comment on list classification: Due to expert review, evidence of 2 unrelated families for loss-of-function variants and further evidence for the role of this gene with an STR reported, this gene has been promoted from Red to Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v1.413 | GLS | Ellen McDonagh Gene: gls has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v1.412 | GLS | Ellen McDonagh Mode of inheritance for gene: GLS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v1.411 | GLS | Ellen McDonagh Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v1.411 | GLS | Ellen McDonagh Added comment: Comment on publications: PMID: 30575854 - 2 families reported with 4 infants who had homozyous/compound heterozygous loss-of-function variants in this gene resulting in early neonatal epileptic encephalopathy with glutaminase deficiency and a lethal outcome. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v1.411 | GLS | Ellen McDonagh Publications for gene: GLS were set to 27604308; 30575854; 29468182 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v1.411 | GLS | Ellen McDonagh Added comment: Comment on publications: PMID: 30575854 - 2 families reported with 4 infants who had homozyous/compound heterozygous loss-of-function variants in this gene resulting in early neonatal epileptic encephalopathy with glutaminase deficiency and a lethal outcome. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v1.411 | GLS | Ellen McDonagh Publications for gene: GLS were set to 27604308; 30575854; 29468182 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v1.410 | GLS | Ellen McDonagh Added comment: Comment on publications: PMID: 30970188 - short tandem repeat (STR) reported in this gene to cause an inborn error of metabolism. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v1.410 | GLS | Ellen McDonagh Publications for gene: GLS were set to 27604308; 30575854; 29468182 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v1.409 | GLS | Ellen McDonagh Publications for gene: GLS were set to 27604308 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v1.47 | GLS |
Ivone Leong Source NHS GMS was added to GLS. Source London North GLH was added to GLS. |
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Likely inborn error of metabolism - targeted testing not possible v0.4 | GLS | Ellen McDonagh Added phenotypes Glucosidase 1 deficiency (Disorders of protein N-glycosylation) for gene: GLS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Likely inborn error of metabolism - targeted testing not possible v0.4 | GLS |
Ellen McDonagh gene: GLS was added gene: GLS was added to Inborn errors of metabolism. Sources: Expert Review Red Mode of inheritance for gene: GLS was set to Unknown Publications for gene: GLS were set to 27604308 Phenotypes for gene: GLS were set to Glucosidase 1 deficiency (Disorders of protein N-glycosylation) |