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Undiagnosed metabolic disorders v1.617 | ADA | Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes: Adenosine deaminase deficiency (Disorders of purine metabolism);Combined B and T cell defect;Infantile enterocolitis & monogenic inflammatory bowel disease;SCID | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.617 | ADA | Arina Puzriakova Phenotypes for gene: ADA were changed from Adenosine deaminase deficiency (Disorders of purine metabolism); Combined B and T cell defect; Infantile enterocolitis & monogenic inflammatory bowel disease; SCID to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.614 | ALAS2 | Arina Puzriakova Phenotypes for gene: ALAS2 were changed from X-linked dominant protoporphyria (Porphyrias with acute painful photosensitivity); X-linked sideroblastic anaemia (XLSA) (Porphyrias with acute painful photosensitivity); Erythropoietic protoporphyria, mild variant to Anemia, sideroblastic, 1, OMIM:300751; Protoporphyria, erythropoietic, X-linked, OMIM:300752 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.612 | TUSC3 | Arina Puzriakova Phenotypes for gene: TUSC3 were changed from TUSC3-CDG (Disorders of protein N-glycosylation); Mental retardation, autosomal recessive 7 to Intellectual developmental disorder, autosomal recessive 7, OMIM:611093 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.609 | ATP5E | Sarah Leigh Classified gene: ATP5E as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.609 | ATP5E | Sarah Leigh Gene: atp5e has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.607 | PIGM |
Sarah Leigh changed review comment from: A single PIGM variant (NM_145167.2(PIGM):c.-270C>G) has been associated with Glycosylphosphatidylinositol deficiency, (OMIM:610293) and as limited Gen2Phen gene for the same condition. To date, this variant has only been reported in people of Arab or Turkish descent. Microsatellite- and SNP-based haplotypes encompassing PIGM reported in PMID:19168132, suggested that a founder effect in the two families (one Arab and one Turkish) was unlikely. However, subsequent occurrences of the variant in two additional unrelated Arab families (PMID: 31445883) might suggest that this variant is confined within the Middle Eastern populations. Functional studies have shown that this variant reduces transcription of PIGM and blocks mannosylation of glycosylphosphatidylinositol anchor (PMID: 16767100).; to: A single PIGM variant (NM_145167.2(PIGM):c.-270C>G)(rs587776528) has been associated with Glycosylphosphatidylinositol deficiency, (OMIM:610293) and as limited Gen2Phen gene for the same condition. To date, this variant has only been reported in people of Arab or Turkish descent. Microsatellite- and SNP-based haplotypes encompassing PIGM reported in PMID:19168132, suggested that a founder effect in the two families (one Arab and one Turkish) was unlikely. However, subsequent occurrences of the variant in two additional unrelated Arab families (PMID: 31445883) might suggest that this variant is confined within the Middle Eastern populations. Functional studies have shown that this variant reduces transcription of PIGM and blocks mannosylation of glycosylphosphatidylinositol anchor (PMID: 16767100). |
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Undiagnosed metabolic disorders v1.607 | PIGM | Sarah Leigh Classified gene: PIGM as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.607 | PIGM | Sarah Leigh Gene: pigm has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.606 | PIGM |
Sarah Leigh edited their review of gene: PIGM: Added comment: A single PIGM variant (NM_145167.2(PIGM):c.-270C>G) has been associated with Glycosylphosphatidylinositol deficiency, (OMIM:610293) and as limited Gen2Phen gene for the same condition. To date, this variant has only been reported in people of Arab or Turkish descent. Microsatellite- and SNP-based haplotypes encompassing PIGM reported in PMID:19168132, suggested that a founder effect in the two families (one Arab and one Turkish) was unlikely. However, subsequent occurrences of the variant in two additional unrelated Arab families (PMID: 31445883) might suggest that this variant is confined within the Middle Eastern populations. Functional studies have shown that this variant reduces transcription of PIGM and blocks mannosylation of glycosylphosphatidylinositol anchor (PMID: 16767100).; Changed rating: GREEN |
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Undiagnosed metabolic disorders v1.605 | PIGM | Sarah Leigh Phenotypes for gene: PIGM were changed from Glycosylphosphatidylinositol deficiency 610293 to Glycosylphosphatidylinositol deficiency, OMIM:610293 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.603 | SEC23B |
Arina Puzriakova Added comment: Comment on mode of inheritance: There is limited evidence linking this gene with Cowden syndrome (monoallelic variants). Only one family has been reported to date (PMID:26522472). This gene:disease association is provisional in OMIM, 'limited' disease confidence category in G2P and is not listed in ClinGen (whereas CDAII is). Biallelic phenotype remains relevant to this panel (PMID: 35163229). On this basis, updating the MOI from 'Both mono- and biallelic' to 'Biallelic' only. |
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Undiagnosed metabolic disorders v1.601 | SLC6A20 | Sarah Leigh Classified gene: SLC6A20 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.601 | SLC6A20 | Sarah Leigh Gene: slc6a20 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.600 | SLC6A20 | Sarah Leigh edited their review of gene: SLC6A20: Added comment: The gene disease associations of SLC6A20 with Hyperglycinuria (OMIM:138500) and Iminoglycinuria, digenic (OMIM:242600) have been refuted in OMIM. The single SLC6A20 variant rs17279437 has been reclassified as a polymorphism, because it is present in 19,986 of 278,932 alleles and in 856 homozygotes in the gnomAD database (v2.1.1), for an allele frequency of 0.07165 (Personal Communication to OMIM from Hamosh, A. Baltimore, Md. 3rd April 2023).; Changed rating: RED; Changed phenotypes to: Hyperglycinuria 138500, Iminoglycinuria, digenic 242600 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.599 | COQ4 | Achchuthan Shanmugasundram Phenotypes for gene: COQ4 were changed from Disorders of CoQ10 biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Coenzyme Q10 deficiency, primary, 7; Disorders of ubiquinone metabolism and biosynthesis to Coenzyme Q10 deficiency, primary, 7, OMIM:616276 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.598 | SLC12A3 | Sarah Leigh Phenotypes for gene: SLC12A3 were changed from Gitelman syndrome (Disorder of magnesium metabolism); Renal tubular acidosis to Gitelman syndrome, OMIM: 263800; Gitelman syndrome, MONDO:0009904 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.587 | OGDH | Sarah Leigh Classified gene: OGDH as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.587 | OGDH | Sarah Leigh Gene: ogdh has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.581 | PC | Arina Puzriakova Phenotypes for gene: PC were changed from Pyruvate carboxylase deficiency (Disorders of gluconeogenesis); lactic acidosis, hypotonia, encephalopathy; Pyruvate carboxylase deficiency 266150; Pyruvate carboxylase deficiency to Pyruvate carboxylase deficiency, OMIM:266150 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.573 | SPG7 | Sarah Leigh edited their review of gene: SPG7: Added comment: Associated with relevant phenotype in OMIM and as definitive Gen2Phen gene. Numerous biallelic SPG7 variants have been reported (PMIDs: 9635427; 16534102; 17646629; 18200586, 20186691; 22571692) and at least five monoallelic SPG7 variants have been associated with Spastic paraplegia 7, autosomal recessive, OMIM:607259 (PMIDs: 18200586; 22571692). For this reason, the mode of inheritance for this gene should be BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form) autosomal or pseudoautosomal.; Changed rating: GREEN; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.573 | SPG7 | Sarah Leigh Phenotypes for gene: SPG7 were changed from Miscellaneous disorders/unknown function (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of mitochondrial DNA maintenance and integrity; Spastic paraplegia 7, autosomal recessive, 607259 to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.570 | COX10 | Arina Puzriakova Phenotypes for gene: COX10 were changed from Complex IV (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors); Isolated complex IV deficiency; Encephalopathy, progressive mitochondrial, with proximal renal tubulopathy due to cytochrome coxidase deficiency; Mitochondrial Diseases; Mitochondrial Respiratory Chain Complex IV Deficiency to Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046; Encephalopathy, progressive mitochondrial, with proximal renal tubulopathy due to cytochrome coxidase deficiency | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.569 | HFE | Arina Puzriakova Phenotypes for gene: HFE were changed from Hereditary haemochromatosis Type 1 (Disorder of iron metabolism); Hemochromatosis, 235200 to Hemochromatosis, OMIM:235200; Disorder of iron metabolism | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.565 | ADAR | Arina Puzriakova Phenotypes for gene: ADAR were changed from Aicardi-Goutieres syndrome 6 615010; Dyschromatosis symmetrica hereditaria 127400 to Aicardi-Goutieres syndrome 6, OMIM:615010; Dyschromatosis symmetrica hereditaria, OMIM:127400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.563 | ST3GAL3 | Sarah Leigh Phenotypes for gene: ST3GAL3 were changed from ST3GAL3-CDG (Disorders of protein N-glycosylation); Intellectual disability to Developmental and epileptic encephalopathy 15, OMIM:615006; developmental and epileptic encephalopathy, 15, MONDO:0014003; Intellectual developmental disorder, autosomal recessive 12, OMIM:611090; intellectual disability, autosomal recessive 12, MONDO:0012612 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.561 | TWNK | Arina Puzriakova Phenotypes for gene: TWNK were changed from Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of mitochondrial DNA maintenance and integrity; Progressive external ophthalmoplegia, autosomal dominant, 3, 609286; Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), 271245; Mitochondrial DNA Depletion Syndrome; Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions (monoallelic); Mitochondrial Membrane Protein-Associated Neurodegeneration (biallelic); Mitochondrial DNA Depletion Syndrome (biallelic) to Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), OMIM:271245; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, OMIM:609286; Perrault syndrome 5, OMIM:616138 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.558 | POLG2 | Arina Puzriakova Phenotypes for gene: POLG2 were changed from Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of mitochondrial DNA maintenance and integrity; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4,610131; Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions to Mitochondrial DNA depletion syndrome syndrome 16 (hepatic type), OMIM:618528; Mitochondrial DNA depletion syndrome 16B (neuroophthalmic type), OMIM:619425; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4, OMIM:610131 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.557 | CLPB | Arina Puzriakova Phenotypes for gene: CLPB were changed from 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, OMIM:616271 to 3-methylglutaconic aciduria, type VIIB, autosomal recessive, OMIM:616271; 3-methylglutaconic aciduria, type VIIA, autosomal dominant, OMIM: 619835; Neutropenia, severe congenital, 9, autosomal dominant, OMIM: 619813 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.553 | LYRM4 | Arina Puzriakova Classified gene: LYRM4 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.553 | LYRM4 | Arina Puzriakova Gene: lyrm4 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.551 | SDHA | Arina Puzriakova Added comment: Comment on mode of inheritance: This gene was recently included on a gene list provided by Carl Fratter (Oxford University Hospitals NHS Trust) on behalf of GMS Mitochondrial providers, indicating that the MOI should be updated from 'biallelic' only to 'both mono- and biallelic' on Mitochondrial GMS panels (R354 and R63). As there was sufficient supporting evidence for the change, the MOI has also been updated to 'both' on this panel to ensure all panels reflect correct knowledge. Heterozygous variants can be associated with abnormal mitochondrial accumulation and therefore also within the scope of the panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.550 | NDUFC2 | Arina Puzriakova Classified gene: NDUFC2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.550 | NDUFC2 | Arina Puzriakova Gene: ndufc2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.547 | NDUFA12 | Arina Puzriakova Classified gene: NDUFA12 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.547 | NDUFA12 | Arina Puzriakova Added comment: Comment on list classification: Gene was recently upgraded from Amber to Green on GMS panels and therefore also updating the rating here to ensure all panels display correct knowledge. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.547 | NDUFA12 | Arina Puzriakova Gene: ndufa12 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.545 | ATP5A1 | Arina Puzriakova Classified gene: ATP5A1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.545 | ATP5A1 | Arina Puzriakova Added comment: Comment on list classification: There is now sufficient evidence to support this gene-disease association and therefore ATP5A1 has been promoted to Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.545 | ATP5A1 | Arina Puzriakova Gene: atp5a1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.543 | ATP5A1 | Arina Puzriakova Added comment: Comment on mode of inheritance: Two families (with two affected sibs each) reported with recessive variants and supported by functional studies (PMIDs: 23599390; 23596069). Six unrelated patients have been reported with heterozygous variants; including one recurrent variant c.620G>A in four cases, c.545G>A and c.1037C>T in the remaining two, respectively (PMIDs: 34483339; 34954817). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.538 | PEX6 | Sarah Leigh changed review comment from: Comment on mode of inheritance: The mode of inheritance for PEX6 has been set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted, in order to highlight that unaffected parents may also carry rs61753230.; to: Comment on mode of inheritance: The mode of inheritance for PEX6 has been set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted for this gene, in order to highlight that unaffected parents may also carry rs61753230. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.534 | PRODH | Sarah Leigh Classified gene: PRODH as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.534 | PRODH |
Sarah Leigh Added comment: Comment on list classification: Evidence for the association of PRODH variants with Hyperprolinemia, type I, OMIM; 239500 has been classified as Definitive by ClinGen Aminoacidopathy Gene Curation Expert Panel on 04/27/2021 (https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_5f28c677-a9b4-4bb3-9aed-14af97ad9896-2021-04-27T160000.000Z). |
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Undiagnosed metabolic disorders v1.534 | PRODH | Sarah Leigh Gene: prodh has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.531 | SLC16A1 | Sarah Leigh changed review comment from: Comment on phenotypes: mainly ketosis with borderline reduction in glucose; Hyperinsulinemic hypoglycemia, familial, 7; to: Comment on phenotypes: Previous phenotype entry: mainly ketosis with borderline reduction in glucose; Hyperinsulinemic hypoglycemia, familial, 7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.531 | SLC16A1 | Sarah Leigh Added comment: Comment on phenotypes: mainly ketosis with borderline reduction in glucose; Hyperinsulinemic hypoglycemia, familial, 7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.531 | SLC16A1 | Sarah Leigh Phenotypes for gene: SLC16A1 were changed from mainly ketosis with borderline reduction in glucose; Hyperinsulinemic hypoglycemia, familial, 7 to Erythrocyte lactate transporter defect, OMIM:245340; Hyperinsulinemic hypoglycemia, familial, 7, OMIM:610021; Monocarboxylate transporter 1 deficiency, OMIM:616095 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.530 | SETX | Sarah Leigh Phenotypes for gene: SETX were changed from Secondary CoQ10 deficiency (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Amyotrophic lateral sclerosis/motor neuron disease; Charcot-Marie-Tooth disease; Hereditary ataxia to Spinocerebellar ataxia, autosomal recessive 1, OMIM:606002; Amyotrophic lateral sclerosis 4, juvenile, OMIM:602433 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.529 | SETX | Sarah Leigh edited their review of gene: SETX: Changed phenotypes to: Spinocerebellar ataxia, autosomal recessive 1, OMIM:606002, Amyotrophic lateral sclerosis 4, juvenile, OMIM:602433 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.529 | AFG3L2 | Arina Puzriakova Phenotypes for gene: AFG3L2 were changed from Miscellaneous disorders/unknown function (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of mitochondrial DNA maintenance and integrity; Spinocerebellar ataxia 28, 610246; Ataxia, spastic, 5, autosomal recessive, 614487 to Optic atrophy 12, OMIM:618977; Spinocerebellar ataxia 28, OMIM:610246; Spastic ataxia 5, autosomal recessive, OMIM:614487 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.527 | OPA1 | Arina Puzriakova Phenotypes for gene: OPA1 were changed from Disorders of mitochondrial dynamics, fusion and fission (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of mitochondrial DNA maintenance and integrity; Optic atrophy 1, 165500; {Glaucoma, normal tension, susceptibility to}, 606657; Optic atrophy plus syndrome, 125250; Mitochondrial DNA Depletion Syndrome; Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions to Optic atrophy 1, OMIM:165500; Optic atrophy plus syndrome, OMIM:125250; Mitochondrial DNA depletion syndrome 14 (encephalocardiomyopathic type), OMIM:616896; Behr syndrome, OMIM:210000 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.526 | MFN2 | Arina Puzriakova Phenotypes for gene: MFN2 were changed from Disorders of mitochondrial dynamics, fusion and fission (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of mitochondrial DNA maintenance and integrity; Charcot-Marie-Tooth disease, type 2A2, 609260; Hereditary motor and sensory neuropathy VI, 601152 to Charcot-Marie-Tooth disease, axonal, type 2A2A, OMIM:609260; Charcot-Marie-Tooth disease, axonal, type 2A2B, OMIM:617087; Hereditary motor and sensory neuropathy VIA, OMIM:601152 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.524 | C19orf12 | Sarah Leigh Phenotypes for gene: C19orf12 were changed from Neurodegeneration with brain iron accumulation (NBIA) (Disorder of iron metabolism); Neurodegeneration with brain iron accumulation 4, 614298; Mitochondrial Membrane Protein-Associated Neurodegeneration to ?Spastic paraplegia 43, autosomal recessive, OMIM:615043; Neurodegeneration with brain iron accumulation 4, OMIM: 614298 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.522 | GDAP1 | Arina Puzriakova Phenotypes for gene: GDAP1 were changed from Charcot Marie Tooth disease (CMT4A); Charcot-Marie-Tooth disease, axonal, type 2K; Charcot-Marie-Tooth disease, axonal, with vocal cord paresis; Charcot-Marie-Tooth disease, recessive intermediate, A; Charcot-Marie-Tooth disease, type 4A to Charcot-Marie-Tooth disease, axonal, type 2K, OMIM:607831; Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, OMIM:607706; Charcot-Marie-Tooth disease, recessive intermediate, A, OMIM:608340; Charcot-Marie-Tooth disease, type 4A, OMIM:214400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.520 | PEX6 | Sarah Leigh Phenotypes for gene: PEX6 were changed from Disorders of peroxisome biogenesis; Peroxisome biogenesis disorder 4A (Zellweger) 614862; Peroxisome biogenesis disorder 4B 614863 to Heimler syndrome 2, OMIM:616617; Peroxisome biogenesis disorder 4A (Zellweger), OMIM:614862; Peroxisome biogenesis disorder 4B, OMIM:614863 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.518 | PEX6 | Sarah Leigh Added comment: Comment on mode of inheritance: The mode of inheritance for PEX6 has been set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted, in order to highlight that unaffected parents may also carry rs61753230. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.517 | PNPT1 | Arina Puzriakova Phenotypes for gene: PNPT1 were changed from Disorders of mitochondrial protein import (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 13, 614932; Deafness, autosomal recessive 70, 614934; respiratory chain disorder; hearing loss to Combined oxidative phosphorylation deficiency 13, OMIM:614932; Deafness, autosomal recessive 70, OMIM:614934; Disorders of mitochondrial protein import (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Multiple respiratory chain complex deficiencies (disorders of protein synthesis) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.508 | CPT2 | Arina Puzriakova Added comment: Comment on mode of inheritance: MOI was updated from 'Biallelic' to 'Both mono- and biallelic'. Although most cases are associated with biallelic variants, symptomatic heterozygous patients have also been described (PMID: 15622536; 21913903; 23184072; 24843804). Severity of symptoms tends to correlate with residual CPT enzyme activity but it is plausible that heterozygotes may still be tested under this panel. Both MOIs are listed in OMIM for this phenotype (MIM# 255110) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.504 | MVK | Arina Puzriakova Phenotypes for gene: MVK were changed from Hyper-IgD syndrome 260920; Mevalonic aciduria 610377; Porokeratosis 3, multiple types 175900 to Hyper-IgD syndrome, OMIM:260920; Mevalonic aciduria, OMIM:610377; Porokeratosis 3, multiple types, OMIM:175900 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.502 | SLC30A10 | Arina Puzriakova Phenotypes for gene: SLC30A10 were changed from Hypermanganesemia with dystonia, polycythemia, and cirrhosis (Disorder of magnesium metabolism); Early onset dystonia; Parkinson Disease and Complex Parkinsonism; Hypermanganesemia with dystonia 1 613280 to Hypermanganesemia with dystonia 1, OMIM:613280 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.501 | HIBADH |
Zornitza Stark gene: HIBADH was added gene: HIBADH was added to Undiagnosed metabolic disorders. Sources: Literature Mode of inheritance for gene: HIBADH was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HIBADH were set to 34176136 Phenotypes for gene: HIBADH were set to organic aciduria Review for gene: HIBADH was set to RED Added comment: Single family reported with two siblings presenting with 3-Hydroxyisobutyric aciduria. Male sib with neurodevelopmental symptoms, female sibling asymptomatic. No functional studies Sources: Literature |
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Undiagnosed metabolic disorders v1.499 | IBA57 | Arina Puzriakova Phenotypes for gene: IBA57 were changed from ?Multiple mitochondrial dysfunctions syndrome 3, 615330; ?Spastic paraplegia 74, autosomal recessive to Multiple mitochondrial dysfunctions syndrome 3, OMIM:615330; ?Spastic paraplegia 74, autosomal recessive, OMIM:616451 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.497 | CLPB |
Arina Puzriakova Added comment: Comment on mode of inheritance: Updated MOI from 'Biallelic' to 'Both mono- and biallelic'. Association between biallelic variants and disease is well established, with more than 35 affected individuals reported. Recently, six unrelated individuals with de novo monoallelic missense variants in CLPB were identified (PMID: 34140661). The phenotype strongly overlapped with that observed in the recessive disease, including 3-MGA-uria in all cases. |
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Undiagnosed metabolic disorders v1.495 | CLPB | Arina Puzriakova Phenotypes for gene: CLPB were changed from 3-methylglutaconic aciduria with the following: cataract, renal cysts and nephrocalcinosis; progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder; cataract, neutropenia, epilepsy; congenital microcephaly and severe encephalopathy to 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, OMIM:616271 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.494 | FXN | Arina Puzriakova Phenotypes for gene: FXN were changed from Friedreich ataxia, 229300; Friedreich ataxia with retained reflexes, 229300; Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) to Friedreich ataxia, OMIM:229300; Friedreich ataxia with retained reflexes, OMIM:229300 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.493 | FXN | Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: FXN. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.493 | 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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.493 | 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.492 | CSTB | Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: CSTB. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.492 | CSTB | Arina Puzriakova Phenotypes for gene: CSTB were changed from Myoclonic epilepsy of Unverricht and Lundborg (Other metabolic disorders); Intellectual disability to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), OMIM:254800 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.489 | ATXN7 | Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.486 | GMPPB | Sarah Leigh Phenotypes for gene: GMPPB were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14 OMIM:615350; muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14 MONDO:0014140; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 14 OMIM:615351; muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14 MONDO:0014141; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 OMIM:615352; autosomal recessive limb-girdle muscular dystrophy type 2T MONDO:0014142 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.481 | C12orf65 | Arina Puzriakova Phenotypes for gene: C12orf65 were changed from Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 7, 613559; Spastic paraplegia 55, autosomal recessive, 615035 to Combined oxidative phosphorylation deficiency 7, OMIM:613559; Spastic paraplegia 55, autosomal recessive, OMIM:615035; Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Multiple respiratory chain complex deficiencies (disorders of protein synthesis) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.480 | SERAC1 | Arina Puzriakova Phenotypes for gene: SERAC1 were changed from Methylglutaconic aciduria with deafness, encephalopathy and Leigh-like syndrome (MEGDEL) (Organic acidurias); Disorders of mitochondrial membrane lipids (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Multiple respiratory chain complex deficiencies (disorders of protein synthesis); 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, 614739 to 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, OMIM:614739; Disorders of mitochondrial membrane lipids (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Multiple respiratory chain complex deficiencies (disorders of protein synthesis) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.479 | FDX2 | Sarah Leigh Phenotypes for gene: FDX2 were changed from Mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy 251900 to Mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy OMIM:251900; mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy MONDO:0020714 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.473 | APOA1 | Sarah Leigh Phenotypes for gene: APOA1 were changed from Apolipoprotein A-I deficiency (Disorders of high density lipoprotein metabolism); Amyloidosis, 3 or more types 105200; ApoA-I and apoC-III deficiency, combined; Corneal clouding, autosomal recessive; Hypoalphalipoproteinemia 604091 to Amyloidosis, 3 or more types OMIM:105200; familial visceral amyloidosis MONDO:0007099; ApoA-I and apoC-III deficiency, combined OMIM:618463; Hypoalphalipoproteinemia, primary, 2, with or without corneal clouding OMIM:618463; hypoalphalipoproteinemia, primary, 2 MONDO:0032766 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.471 | COQ2 |
Ivone Leong Added comment: Comment on phenotypes: Previously: Disorders of CoQ10 biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Disorders of ubiquinone metabolism and biosynthesis;Coenzyme Q10 deficiency, primary, 1, 607426;Coenzyme Q10 deficiency;{Multiple system atrophy, susceptibility to}, 146500 |
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Undiagnosed metabolic disorders v1.471 | COQ2 | Ivone Leong Phenotypes for gene: COQ2 were changed from Disorders of CoQ10 biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of ubiquinone metabolism and biosynthesis; Coenzyme Q10 deficiency, primary, 1, 607426; Coenzyme Q10 deficiency; {Multiple system atrophy, susceptibility to}, 146500 to Coenzyme Q10 deficiency, primary, 1, OMIM:607426 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.468 | ALDH18A1 | Sarah Leigh Added comment: Comment on phenotypes: Hypoprolinaemia, Cutis laxa, autosomal recessive, type IIIa (Disorders of ornithine or proline metabolism);Cutis laxa, autosomal recessive, type IIIA (Delta-1-pyrroline 5 carboxylic acid synthetase deficiency) 219150 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.468 | ALDH18A1 | Sarah Leigh Phenotypes for gene: ALDH18A1 were changed from Hypoprolinaemia, Cutis laxa, autosomal recessive, type IIIa (Disorders of ornithine or proline metabolism); Cutis laxa, autosomal recessive, type IIIA (Delta-1-pyrroline 5 carboxylic acid synthetase deficiency) 219150 to Cutis laxa, autosomal dominant 3 OMIM:616603; cutis laxa, autosomal dominant 3 MONDO:0014706; Cutis laxa, autosomal recessive, type IIIA OMIM:219150; ALDH18A1-related de Barsy syndrome MONDO:0009053; Spastic paraplegia 9A, autosomal dominant OMIM:601162; hereditary spastic paraplegia 9A MONDO:0011006; Spastic paraplegia 9B, autosomal recessive OMIM:616586; autosomal recessive complex spastic paraplegia type 9B MONDO:0014702 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.466 | ATAD3A | Arina Puzriakova Phenotypes for gene: ATAD3A were changed from Lactic acidosis; Methylglutaconic aciduria; Neurological abnormalities; Cerebellar hypoplasia; Optic atrophy; Hypertrophic cardiomyopathy; Scoliosis; Spinal muscular atrophy to Harel-Yoon syndrome, OMIM:617183; Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal, OMIM:618810; Lactic acidosis; Methylglutaconic aciduria | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.461 | SLC17A5 | Arina Puzriakova Phenotypes for gene: SLC17A5 were changed from Salla disease 604369; Sialic acid storage disorder, infantile 269920 to Salla disease, OMIM:604369; Sialic acid storage disorder, infantile, OMIM:269920 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.458 | NFU1 | Arina Puzriakova Phenotypes for gene: NFU1 were changed from Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Multiple mitochondrial dysfunctions syndrome 1 to Multiple mitochondrial dysfunctions syndrome 1, OMIM:605711; Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.451 | LARS2 | Arina Puzriakova Phenotypes for gene: LARS2 were changed from Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Perrault syndrome 4, 615300; Perrault syndrome to Perrault syndrome 4, OMIM:615300; Hydrops, lactic acidosis, and sideroblastic anemia, OMIM:617021; Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only); Multiple respiratory chain complex deficiencies (disorders of protein synthesis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.450 | CLN5 | Sarah Leigh Phenotypes for gene: CLN5 were changed from Ceroid lipofuscinosis, neuronal, 5 256731 to Ceroid lipofuscinosis, neuronal, 5 OMIM:256731; neuronal ceroid lipofuscinosis 5 MONDO:0009745 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.449 | GNE | Sarah Leigh Phenotypes for gene: GNE were changed from UDP-GlcNAc epimerase/kinase deficiency (Disorders of multiple glycosylation and other glycosylation pathways); Sialuria (Other lysosomal disorders); Nonaka myopathy 605820; ADUDP-GlcNAc epimerase/kinase deficiency (Disorders of multiple glycosylation and other glycosylation pathways) to Sialuria OMIM:269921; sialuria MONDO:0010028; Nonaka myopathy OMIM:605820; GNE myopathy MONDO:0011603 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.445 | NDUFC2 | Sarah Leigh Classified gene: NDUFC2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.445 | NDUFC2 | Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.445 | NDUFC2 | Sarah Leigh Gene: ndufc2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.444 | NDUFC2 | Sarah Leigh commented on gene: NDUFC2: Associated with relevant phenotype in OMIM, but not Gen2Phen. At least 2 variants have been reported in two unrelated cases, together with supportive functional evidence (PMID 32969598). There are also 2 families with complex I deficiency with reported by Carl Fratter (10 May 2019, Oxford University Hospitals NHS Trust). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.442 | MAGT1 | Sarah Leigh Phenotypes for gene: MAGT1 were changed from Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia 300853 to Congenital disorder of glycosylation, type Icc OMIM:301031; congenital disorder of glycosylation, type ICC MONDO:0026729; Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia OMIM:300853; X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia MONDO:0010455 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.441 | MSMO1 | Arina Puzriakova Phenotypes for gene: MSMO1 were changed from Sterol-C4-methyl oxidase deficiency (Disorders of sterol biosynthesis); Microcephaly, congenital cataract, and psoriasiform dermatitis, 616834; (SC4MOL DEFICIENCY) to Sterol-C4-methyl oxidase deficiency (Disorders of sterol biosynthesis); Microcephaly, congenital cataract, and psoriasiform dermatitis, OMIM:616834; Microcephaly-congenital cataract-psoriasiform dermatitis syndrome, MONDO:0014793 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.440 | GLS | Arina Puzriakova Classified gene: GLS as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.440 | GLS |
Arina Puzriakova Added comment: Comment on list classification: Upgraded from Red to Amber. There are sufficient cases, supported by functional data, to rate this gene Green - however, detection of the 5' UTR triplet expansion (PMID:30970188) must first be 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 keeping Amber until the STR is validated or additional cases arise. |
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Undiagnosed metabolic disorders v1.440 | GLS | Arina Puzriakova Gene: gls has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.439 | GLS | Arina Puzriakova Phenotypes for gene: GLS were changed from Glucosidase 1 deficiency (Disorders of protein N-glycosylation) 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.436 | GLS | Arina Puzriakova reviewed gene: GLS: Rating: GREEN; 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.434 | HS2ST1 | Ivone Leong Classified gene: HS2ST1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.434 | HS2ST1 | Ivone Leong Gene: hs2st1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.433 | HS2ST1 |
Ivone Leong gene: HS2ST1 was added gene: HS2ST1 was added to Undiagnosed metabolic disorders. Sources: Literature Mode of inheritance for gene: HS2ST1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: HS2ST1 were set to 33159882 Phenotypes for gene: HS2ST1 were set to Intellectual disability; dysmorphic features; congenital anomalies Review for gene: HS2ST1 was set to GREEN Added comment: This gene is not associated with a relevant phenotype in OMIM or Gene2Phenotype. Only 2 of 3 unrelated families with affected individuals described in PMID: 33159882 were reported to have ID. The affected individuals in the third family could not be assessed for ID. Other features affected individuals had were muscular hypotonia, hypoplasia/agenesis of corpus callosum, skeletal abnormalities, uni/bilateral renal agenesis (2/3) and craniofacial dysmorphism. There is enough evidence to support a gene-disease association, so this gene has been rated Green. Sources: Literature |
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Undiagnosed metabolic disorders v1.432 | AASS | Arina Puzriakova Phenotypes for gene: AASS were changed from Hyperlysinaemia (Disorders of histidine, tryptophan or lysine metabolism); Intellectual disability; Hyperlysinemia 238700 to Hyperlysinemia, OMIM:238700; Hyperlysinemia (disease), MONDO:0009388 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.425 | ALG14 | Arina Puzriakova Classified gene: ALG14 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.425 | ALG14 | Arina Puzriakova Gene: alg14 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.424 | AHCY | Arina Puzriakova Classified gene: AHCY as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.424 | AHCY | Arina Puzriakova Added comment: Comment on list classification: Promoted from Red to Green - multiple unrelated families with this neurometabolic disorder caused by biallelic variants in AHCY. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.424 | AHCY | Arina Puzriakova Gene: ahcy has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.423 | XYLT1 | Arina Puzriakova Phenotypes for gene: XYLT1 were changed from Desbuquois dysplasia 2 to Desbuquois dysplasia 2, 615777 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.420 | AHCY | Arina Puzriakova Classified gene: AHCY as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.420 | AHCY | Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to rate this gene GREEN at the next major review - multiple unrelated families with this neurometabolic disorder caused by variants in AHCY. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.420 | AHCY | Arina Puzriakova Gene: ahcy has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.417 | ALG14 | Sarah Leigh Classified gene: ALG14 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.417 | ALG14 | Sarah Leigh Added comment: Comment on list classification: Associated with Myasthenic syndrome, congenital, 15, without tubular aggregates 616227 in OMIM, but not associated with phenotype in Gen2Phen. At least 6 variants reported in at least 5 cases with varying phenotypes. PMID 23404334 reports compound heterozygous (p.P65L, P.R104*) sibs, who manifested with myasthenic syndromes, but did not have intellectural disability nor seizures and were 62 and 51 years old when reported. PMID 28733338 reports two compound heterozygous (p.D74N, pV141G), (p.D74N, p.R109Q) cases and a homozygous (p.D74N), with early and lethal neurodegeneration with myasthenic and myopathic features, but the cases died before intellectual disability was manifiest. However, seizures were evident in two compound heterozygous families. PMID 30221345 reports a homozygous splicing variant in a case with intellectual disability and seizures. Functional studies were presented showing that this variant resulting in exon skipping, however, this was not completely prenetrant as wild type protein was detected at a low level in the patient. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.417 | ALG14 | Sarah Leigh Gene: alg14 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.413 | DDC | Lothar Schlueter reviewed gene: DDC: Rating: GREEN; Mode of pathogenicity: None; Publications: 28100251, 30952622; Phenotypes: Aromatic L-amino acid decarboxylase deficiency 608643, floppy child, dystonia, hypotonia, developmental delay, oculogyric crisis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.411 | SETX | Catherine Snow Classified gene: SETX as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.411 | SETX | Catherine Snow Gene: setx has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.410 | SETX | Catherine Snow reviewed gene: SETX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Amyotrophic lateral sclerosis 4, juvenile, 602433, Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2, 606002; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.410 | SKIV2L | Catherine Snow Classified gene: SKIV2L as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.410 | SKIV2L | Catherine Snow Gene: skiv2l has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.409 | SLC12A3 | Catherine Snow Classified gene: SLC12A3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.409 | SLC12A3 | Catherine Snow Gene: slc12a3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.408 | SLC18A2 | Catherine Snow Classified gene: SLC18A2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.408 | SLC18A2 | Catherine Snow Gene: slc18a2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.407 | SLC35A2 | Catherine Snow Classified gene: SLC35A2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.407 | SLC35A2 | Catherine Snow Gene: slc35a2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.406 | SLC3A1 | Catherine Snow Classified gene: SLC3A1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.406 | SLC3A1 | Catherine Snow Gene: slc3a1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.403 | SLC6A3 | Catherine Snow Classified gene: SLC6A3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.403 | SLC6A3 | Catherine Snow Added comment: Comment on list classification: ted from Amber to Green. SLC6A3 is associated with an appropriate phenotype on OMIM. There are >3 unrelated cases listed on OMIM. Therefore, enough evidence for this gene to be promoted to Green status. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.403 | SLC6A3 | Catherine Snow Gene: slc6a3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.402 | RBP4 | Ivone Leong Classified gene: RBP4 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.402 | RBP4 | Ivone Leong Added comment: Comment on list classification: Promoted from Amber to Green. RBP4 is associated with retinoid metabolism on OMIM, but not on Gene2Phenotype. There are >3 unrelated cases listed on OMIM. Therefore, enough evidence for this gene to be promoted to Green status. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.402 | RBP4 | Ivone Leong Gene: rbp4 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.401 | SLC6A8 | Catherine Snow Classified gene: SLC6A8 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.401 | SLC6A8 | Catherine Snow Gene: slc6a8 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.400 | SLC7A9 | Catherine Snow Classified gene: SLC7A9 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.400 | SLC7A9 | Catherine Snow Gene: slc7a9 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.399 | NNT | Catherine Snow Classified gene: NNT as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.399 | NNT | Catherine Snow Gene: nnt has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.398 | NNT |
Catherine Snow gene: NNT was added gene: NNT was added to Undiagnosed metabolic disorders. Sources: Expert Review Mode of inheritance for gene: NNT was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NNT were set to 27129361; 28546232 Phenotypes for gene: NNT were set to Glucocorticoid deficiency 4, with or without mineralocorticoid deficiency, 614736 Review for gene: NNT was set to GREEN Added comment: Relevant phenotype in OMIM but not in Gene2Phenotype. Sufficient cases in OMIM to classify NNT as Green Sources: Expert Review |
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Undiagnosed metabolic disorders v1.397 | TRAP1 | Catherine Snow Classified gene: TRAP1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.397 | TRAP1 | Catherine Snow Gene: trap1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.396 | TRAP1 |
Catherine Snow gene: TRAP1 was added gene: TRAP1 was added to Undiagnosed metabolic disorders. Sources: Expert list Mode of inheritance for gene: TRAP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TRAP1 were set to 24152966 Phenotypes for gene: TRAP1 were set to VACTERL; CAKUT Review for gene: TRAP1 was set to GREEN Added comment: Not in OMIM or Gene2Phenotype. Recessive mutations reported in 2 families with CAKUT, and 3 families with VACTERL. Metabolism phenotype as the encoded protein has ATPase activity and interacts with tumor necrosis factor type I. Sources: Expert list |
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Undiagnosed metabolic disorders v1.395 | MRPL12 |
Catherine Snow gene: MRPL12 was added gene: MRPL12 was added to Undiagnosed metabolic disorders. Sources: Expert list Mode of inheritance for gene: MRPL12 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MRPL12 were set to 23603806 Phenotypes for gene: MRPL12 were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis) Review for gene: MRPL12 was set to RED Added comment: A single reported family in the literature therefore classified as Red. Sources: Expert list |
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Undiagnosed metabolic disorders v1.394 | LYRM4 |
Catherine Snow gene: LYRM4 was added gene: LYRM4 was added to Undiagnosed metabolic disorders. Sources: Expert Review Mode of inheritance for gene: LYRM4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LYRM4 were set to 23814038 Phenotypes for gene: LYRM4 were set to ?Combined oxidative phosphorylation deficiency 19, 615595 Review for gene: LYRM4 was set to AMBER Added comment: LYRM4 is in OMIM but not in Gene2Phenotype. Two related patients in PMID 23814038 and some functional work. As <3 unrelated patients, classifying LYRM4 as Amber. Sources: Expert Review |
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Undiagnosed metabolic disorders v1.393 | LARS | Catherine Snow Classified gene: LARS as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.393 | LARS | Catherine Snow Gene: lars has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.392 | LARS |
Catherine Snow changed review comment from: LARS1 has a relevant phenotype and is in OMIM, but not in Gene2Phenotype. PMID: 30349989 describes a premature girl who was identified to have compound hetrozygous variants in LARS1, this has caused infantile liver failure syndrome, type 1 (ILFS1). The paper also summarised the clinical features of reported patients with infantile liver failure syndrome type 1 caused by cytosolic leucine-tRNA synthetase deficiency, in total 6 compound hetrozygous variants identified in 14 patients in 7 families. Sufficient variants and relevant phenotype to upgrade LARS1 from Red to Green. Sources: Expert Review; to: LARS1 has a relevant phenotype and is in OMIM, but not in Gene2Phenotype. PMID: 30349989 describes a premature girl who was identified to have compound hetrozygous variants in LARS1, this has caused infantile liver failure syndrome, type 1 (ILFS1). The paper also summarised the clinical features of reported patients with infantile liver failure syndrome type 1 caused by cytosolic leucine-tRNA synthetase deficiency, in total 6 compound hetrozygous variants identified in 14 patients in 7 families. Sufficient variants and relevant phenotype to classify LARS1 as Green. Sources: Expert Review |
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Undiagnosed metabolic disorders v1.390 | TTC37 | Catherine Snow Classified gene: TTC37 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.390 | TTC37 | Catherine Snow Gene: ttc37 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.388 | ST3GAL3 | Catherine Snow Classified gene: ST3GAL3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.388 | ST3GAL3 | Catherine Snow Gene: st3gal3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.387 | ST3GAL3 | Catherine Snow reviewed gene: ST3GAL3: Rating: GREEN; Mode of pathogenicity: None; Publications: 21907012, 23252400, 31584066; Phenotypes: Epileptic encephalopathy, early infantile, 15, 615006: Mental retardation, autosomal recessive 12, 611090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.387 | TH | Catherine Snow reviewed gene: TH: Rating: GREEN; Mode of pathogenicity: None; Publications: 24753243; Phenotypes: Segawa syndrome, recessive, 605407; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.386 | WFS1 | Catherine Snow Classified gene: WFS1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.386 | WFS1 | Catherine Snow Added comment: Comment on list classification: Promoted from Amber to Green. WFS1 is associated with an appropriate phenotype on OMIM and Gene2Phenotype. There are >3 unrelated cases listed on OMIM. Therefore, enough evidence for this gene to be promoted to Green status. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.386 | WFS1 | Catherine Snow Gene: wfs1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.385 | VKORC1 | Catherine Snow changed review comment from: Comment on list classification: Promoted from Amber to Green. PTS is associated with an appropriate phenotype on OMIM and Gene2Phenotype. There are >3 unrelated cases listed on OMIM. Therefore, enough evidence for this gene to be promoted to Green status.; to: Comment on list classification: Promoted from Amber to Green. VKORC1 is associated with an appropriate phenotype on OMIM and Gene2Phenotype. There are >3 unrelated cases listed on OMIM. Therefore, enough evidence for this gene to be promoted to Green status. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.385 | VKORC1 | Catherine Snow Classified gene: VKORC1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.385 | VKORC1 | Catherine Snow Gene: vkorc1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.384 | VKORC1 | Catherine Snow reviewed gene: VKORC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Vitamin K-dependent clotting factors, combined deficiency of, 2, 607473, Warfarin resistance, 122700; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.384 | VIPAS39 | Catherine Snow Classified gene: VIPAS39 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.384 | VIPAS39 | Catherine Snow Gene: vipas39 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.382 | VPS33B | Catherine Snow Classified gene: VPS33B as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.382 | VPS33B | Catherine Snow Gene: vps33b has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.381 | VPS33B | Catherine Snow reviewed gene: VPS33B: Rating: GREEN; Mode of pathogenicity: None; Publications: 18853461; Phenotypes: Arthrogryposis, renal dysfunction, and cholestasis 1, 208085; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.381 | UQCRB | Catherine Snow Classified gene: UQCRB as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.381 | UQCRB | Catherine Snow Gene: uqcrb has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.379 | UMOD | Catherine Snow Classified gene: UMOD as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.379 | UMOD | Catherine Snow Gene: umod has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.378 | TUFM | Catherine Snow Classified gene: TUFM as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.378 | TUFM | Catherine Snow Gene: tufm has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.376 | TTPA | Catherine Snow Classified gene: TTPA as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.376 | TTPA | Catherine Snow Gene: ttpa has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.374 | TREX1 | Catherine Snow Classified gene: TREX1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.374 | TREX1 | Catherine Snow Gene: trex1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.372 | TCN2 | Catherine Snow Classified gene: TCN2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.372 | TCN2 | Catherine Snow Gene: tcn2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.370 | TAT | Catherine Snow Classified gene: TAT as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.370 | TAT | Catherine Snow Gene: tat has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.368 | STS |
Catherine Snow changed review comment from: Comment on list classification: Promoted from Amber to Green. This gene is associated with a relevant disease on OMIM and Gene2Phenotype and there is enough evidence to support a gene-disease association. This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype.; to: Comment on list classification: Promoted from Amber to Green. This gene is associated with a relevant disease on OMIM and Gene2Phenotype and there is enough evidence to support a gene-disease association. |
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Undiagnosed metabolic disorders v1.367 | STS | Catherine Snow Classified gene: STS as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.367 | STS | Catherine Snow Gene: sts has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.366 | STS | Catherine Snow reviewed gene: STS: Rating: GREEN; Mode of pathogenicity: None; Publications: 1539590, 29672931; Phenotypes: Ichthyosis, X-linked, 308100; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.366 | ISCA2 | Sarah Leigh Classified gene: ISCA2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.366 | ISCA2 | Sarah Leigh Gene: isca2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.364 | DNM2 | Sarah Leigh Classified gene: DNM2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.364 | DNM2 | Sarah Leigh Added comment: Comment on list classification: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: 1 case with multiple deletions and COX negative fibres; 5 cases presented in a poster with dominant DMN2 variants (had COX deficient muscle fibres, one case with the p.Arg369Trp revealed disruption of the dynamic mitochondrial network, https://doi.org/10.1016/j.nmd.2012.06.124). From panels: Possible mitochondrial disorder - nuclear genes (Version 0.187) and Mitochondrial DNA maintenance disorder (Version 0.8). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.364 | DNM2 | Sarah Leigh Gene: dnm2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.361 | SLC2A1 | Ivone Leong Classified gene: SLC2A1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.361 | SLC2A1 | Ivone Leong Added comment: Comment on list classification: Promoted from Amber to Green. SLC2A1 is associated with GLUT1 deficiency syndrome 1 and GLUT1 deficiency syndrome 2 on OMIM and Gene2Phenotype. There are >3 unrelated cases reported on OMIM. Therefore, there is enough evidence for this gene to be promoted to Green status. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.361 | SLC2A1 | Ivone Leong Gene: slc2a1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.360 | HSPA9 | Sarah Leigh Classified gene: HSPA9 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.360 | HSPA9 | Sarah Leigh Gene: hspa9 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.359 | HSPA9 | Sarah Leigh Added comment: Comment on phenotypes: Monoallelic variants reported in Anemia, sideroblastic, 4 182170. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.357 | FDX2 | Sarah Leigh Classified gene: FDX2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.357 | FDX2 |
Sarah Leigh Added comment: Comment on list classification: Based on reviews from Carl Fratter and Zornitza Stark (below). This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: 3 unrelated familties; iron sulfur pathway. From panel: Possible mitochondrial disorder - nuclear genes (Version 0.187). Promoted from red to amber, based on the expert review by Zornitza Stark (Australian Genomics) and the literature. FDX2 is associated with a phenotype in OMIM and not Gene2Phenotype. PMID: 24281368 describes a patient born of consanguineous Jewish Moroccan patents with episodic mitochondrial myopathy without optic atrophy or reversible leukoencephalopathy. The authors identified a homozygous missense variant in this gene (M1L). PMID: 30010796 describes 6 patients from 2 apparently unrelated Brazilian familes from the same geographical region with episodic mitochondrial myopathy. All affected individuals had the same homozygous variant (P144L). No haplotype analysis was performed. As there are only 2 different variants reported in this gene and no haplotype analysis was performed in PMID: 30010796 it was decided that there is currently not enough evidence to promote this gene to green status. |
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Undiagnosed metabolic disorders v1.357 | FDX2 | Sarah Leigh Gene: fdx2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.356 | FDX2 |
Sarah Leigh gene: FDX2 was added gene: FDX2 was added to Undiagnosed metabolic disorders. Sources: Literature Mode of inheritance for gene: FDX2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FDX2 were set to 24281368; 28803783; 30010796 Phenotypes for gene: FDX2 were set to Mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy 251900 Review for gene: FDX2 was set to GREEN Added comment: Sources: Literature |
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Undiagnosed metabolic disorders v1.350 | COX8A |
Sarah Leigh gene: COX8A was added gene: COX8A was added to Undiagnosed metabolic disorders. Sources: Literature Mode of inheritance for gene: COX8A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COX8A were set to 26685157 Phenotypes for gene: COX8A were set to ?Mitochondrial complex IV deficiency 220110 Review for gene: COX8A was set to RED Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 1 variant reported in a 12.5-year old girl, born of Turkish parents who were likely distantly related, with mitochondrial complex I deficiency. The proband died from cardiorespiratory failure associated with infection and metabolic crisis at 12.5 years. No further variants reported to date (30/09/2019). Sources: Literature |
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Undiagnosed metabolic disorders v1.349 | COQ7 | Sarah Leigh Classified gene: COQ7 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.349 | COQ7 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 2 variants reported in unrelated cases, together with supportive functional studies. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.349 | COQ7 | Sarah Leigh Gene: coq7 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.348 | COQ7 |
Sarah Leigh gene: COQ7 was added gene: COQ7 was added to Undiagnosed metabolic disorders. Sources: Literature Mode of inheritance for gene: COQ7 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COQ7 were set to 26084283; 28409910 Phenotypes for gene: COQ7 were set to ?Coenzyme Q10 deficiency, primary, 8 616733 Review for gene: COQ7 was set to GREEN Added comment: This gene was added as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: 3 unrelated individuals and functional studies. From panel: Possible mitochondrial disorder - nuclear genes (Version 0.187). Sources: Literature |
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Undiagnosed metabolic disorders v1.347 | TMEM126A | Sarah Leigh Classified gene: TMEM126A as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.347 | TMEM126A |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with the phenotype Optic atrophy 7 612989 in OMIM, but not associated with phenotype in Gen2Phen. At least 2 variants reported in unrelated cases. The red rating is based on Helen Britain's opinion that, the phenotype of Optic atrophy 7 612989 will not present via a metabolic team. TMEM126A is green on the Optic neuropathy panel. |
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Undiagnosed metabolic disorders v1.347 | TMEM126A | Sarah Leigh Gene: tmem126a has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.344 | PDK3 | Sarah Leigh Classified gene: PDK3 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.344 | PDK3 |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 2 variants reported in at least three unrelated cases, together with functional studies. |
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Undiagnosed metabolic disorders v1.344 | PDK3 | Sarah Leigh Gene: pdk3 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.342 | PDK1 |
Sarah Leigh changed review comment from: Comment on list classification: Not associated with phenotype in OMIM or in Gen2Phen. PDK1 is mentioned in the supplimentary material in PMID 27604308, however, no details of variants nor phenotypes are mentioned.; to: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Not associated with phenotype in OMIM or in Gen2Phen. PDK1 is mentioned in the supplimentary material in PMID 27604308, however, no details of variants nor phenotypes are mentioned. |
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Undiagnosed metabolic disorders v1.342 | NDUFA12 |
Sarah Leigh changed review comment from: Comment on list classification: Amber review collated by Carl Fratter May 2019 on behalf of GMS mitochondrial specialist test group: One case with a single homozygous terminating variant, together with functional studies.; to: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Amber review collated by Carl Fratter May 2019 on behalf of GMS mitochondrial specialist test group: One case with a single homozygous terminating variant, together with functional studies. |
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Undiagnosed metabolic disorders v1.342 | MRPS16 |
Sarah Leigh changed review comment from: Comment on list classification: Amber review collated by Carl Fratter May 2019 on behalf of GMS mitochondrial specialist test group: single homozygous terminating variant in two 'unrelated' cases, together with functional studies.; to: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Amber review collated by Carl Fratter May 2019 on behalf of GMS mitochondrial specialist test group: single homozygous terminating variant in two 'unrelated' cases, together with functional studies. |
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Undiagnosed metabolic disorders v1.342 | COX4I2 |
Sarah Leigh changed review comment from: Comment on list classification: This gene should remain Amber due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter. One homozygous variant (c.412G>A, p.E138K) reported in 5 Arab Muslim patients with exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis (612714) (PMID 19268275) and heterozygous variant (c.253C>T, p.R85W) found together with a heterozygous COX10 variant (c.1096G>T, p.V366L)(PMID 22592081).; to: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. This gene should remain Amber due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter. One homozygous variant (c.412G>A, p.E138K) reported in 5 Arab Muslim patients with exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis (612714) (PMID 19268275) and heterozygous variant (c.253C>T, p.R85W) found together with a heterozygous COX10 variant (c.1096G>T, p.V366L)(PMID 22592081). |
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Undiagnosed metabolic disorders v1.342 | COA5 | Sarah Leigh changed review comment from: Associated with phenotype in OMIM and as a possible G2P. At least 1 variant reported.; to: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with phenotype in OMIM and as a possible G2P. At least 1 variant reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.342 | ATP5E | Sarah Leigh changed review comment from: Comment on list classification: Updated information and Amber review collated by Carl Fratter May 2019 on behalf of GMS mitochondrial specialist test group: 1 reported case with functional studies.; to: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Updated information and Amber review collated by Carl Fratter May 2019 on behalf of GMS mitochondrial specialist test group: 1 reported case with functional studies. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.342 | ATP5A1 | Sarah Leigh changed review comment from: Comment on list classification: Two variants together with functional studies. The Amber rating is based on the views of Anna de Burca (Genomics England Clinical Fellow) that the interpretation of PMID 23599390 that the boys in this publication have inherited a heterozygous variant from their father while not expressing the maternal allele due to unknown variant affecting expression.; to: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. The Amber rating is based on the views of Anna de Burca (Genomics England Clinical Fellow) that the interpretation of PMID 23599390 that the boys in this publication have inherited a heterozygous variant from their father while not expressing the maternal allele due to unknown variant affecting expression. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.338 | PDK1 | Sarah Leigh Classified gene: PDK1 as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.338 | PDK1 | Sarah Leigh Added comment: Comment on list classification: Not associated with phenotype in OMIM or in Gen2Phen. PDK1 is mentioned in the supplimentary material in PMID 27604308, however, no details of variants nor phenotypes are mentioned. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.338 | PDK1 | Sarah Leigh Gene: pdk1 has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.335 | NDUFA12 | Sarah Leigh Classified gene: NDUFA12 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.335 | NDUFA12 | Sarah Leigh Added comment: Comment on list classification: Amber review collated by Carl Fratter May 2019 on behalf of GMS mitochondrial specialist test group: One case with a single homozygous terminating variant, together with functional studies. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.335 | NDUFA12 | Sarah Leigh Gene: ndufa12 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.333 | MRPS16 | Sarah Leigh Classified gene: MRPS16 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.333 | MRPS16 | Sarah Leigh Added comment: Comment on list classification: Amber review collated by Carl Fratter May 2019 on behalf of GMS mitochondrial specialist test group: single homozygous terminating variant in two 'unrelated' cases, together with functional studies. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.333 | MRPS16 | Sarah Leigh Gene: mrps16 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.332 | MRPS16 | Sarah Leigh Added comment: Comment on phenotypes: Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); CORPUS CALLOSUM, AGENESIS OF, WITH DYSMORPHISM AND FATAL LACTIC ACIDOSIS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.332 | MRPS16 | Sarah Leigh Phenotypes for gene: MRPS16 were changed from Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Combined oxidative phosphorylation deficiency 2, 610498; CORPUS CALLOSUM, AGENESIS OF, WITH DYSMORPHISM AND FATAL LACTIC ACIDOSIS to Combined oxidative phosphorylation deficiency 2 610498 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.330 | COX4I2 | Sarah Leigh Phenotypes for gene: COX4I2 were changed from Complex IV (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits); Exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis 612714 to Exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis 612714 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.328 | COX4I2 | Sarah Leigh Classified gene: COX4I2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.328 | COX4I2 |
Sarah Leigh Added comment: Comment on list classification: This gene should remain Amber due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter. One homozygous variant (c.412G>A, p.E138K) reported in 5 Arab Muslim patients with exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis (612714) (PMID 19268275) and heterozygous variant (c.253C>T, p.R85W) found together with a heterozygous COX10 variant (c.1096G>T, p.V366L)(PMID 22592081). |
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Undiagnosed metabolic disorders v1.328 | COX4I2 | Sarah Leigh Gene: cox4i2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.325 | ATP5E | Sarah Leigh Classified gene: ATP5E as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.325 | ATP5E | Sarah Leigh Gene: atp5e has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.320 | ATP5E | Sarah Leigh Classified gene: ATP5E as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.320 | ATP5E | Sarah Leigh Added comment: Comment on list classification: Updated information and Amber review collated by Carl Fratter May 2019 on behalf of GMS mitochondrial specialist test group: 1 reported case with functional studies. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.320 | ATP5E | Sarah Leigh Gene: atp5e has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.316 | ATP5A1 | Sarah Leigh changed review comment from: Comment on list classification: Two variants together with functional studies. The Amber rating is based on the views of Anna de Burca (Genomics England Clinical Fellow) that the interpretation of PMID 23599390 that the boys have inherited a heterozygous variant from their father while not expressing the maternal allele due to unknown variant affecting expression.; to: Comment on list classification: Two variants together with functional studies. The Amber rating is based on the views of Anna de Burca (Genomics England Clinical Fellow) that the interpretation of PMID 23599390 that the boys in this publication have inherited a heterozygous variant from their father while not expressing the maternal allele due to unknown variant affecting expression. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.315 | SPTLC1 | Catherine Snow Classified gene: SPTLC1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.315 | SPTLC1 | Catherine Snow Gene: sptlc1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.313 | SPTLC2 | Catherine Snow Classified gene: SPTLC2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.313 | SPTLC2 | Catherine Snow Gene: sptlc2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.312 | SPR | Catherine Snow changed review comment from: Promoted from Amber to Green. This gene is associated with a relevant disease on OMIM and Gene2Phenotype and there is enough evidence to support a gene-disease association. Sepiapterin reductase (SR) deficiency leads to altered tetrahydrobiopterin (BH4) biosynthesis and abnormal biogenic amine metabolism. Most individuals improve with L-dopa administration, therefore treatable tag has been added.; to: Promoted from Amber to Green. This gene is associated with a relevant disease in OMIM and Gene2Phenotype and there is enough evidence to support a gene-disease association. Sepiapterin reductase (SR) deficiency leads to altered tetrahydrobiopterin (BH4) biosynthesis and abnormal biogenic amine metabolism. Most individuals improve with L-dopa administration, therefore treatable tag has been added. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.311 | SPR | Catherine Snow Classified gene: SPR as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.311 | SPR | Catherine Snow Gene: spr has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.310 | SPR | Catherine Snow reviewed gene: SPR: Rating: GREEN; Mode of pathogenicity: None; Publications: 22018912, 22522443, 22018912, 24588500, 28189489, 21431957, 16650784; Phenotypes: Dystonia, dopa-responsive, due to sepiapterin reductase deficiency 612716; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.310 | SLC25A12 | Ivone Leong Classified gene: SLC25A12 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.310 | SLC25A12 | Ivone Leong Added comment: Comment on list classification: Promoted from Amber to Green. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 biallelic variants reported in unrelated cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.310 | SLC25A12 | Ivone Leong Gene: slc25a12 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.306 | SC5D | Ivone Leong Classified gene: SC5D as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.306 | SC5D | Ivone Leong Added comment: Comment on list classification: Promoted from Amber to Green. This gene is associated with a relevant disease on OMIM and Gene2Phenotype and there is enough evidence to support a gene-disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.306 | SC5D | Ivone Leong Gene: sc5d has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.305 | RNASEH2B | Ivone Leong changed review comment from: Comment on list classification: Demoted from Amber to Red. RNASEH2B is associated with Aicardi-Goutieres syndrome 2 on OMIM and Gene2Phenotype. There are 2 unrelated cases on OMIM supporting the gene-disease link between RNASEH2B with Aicardi-Goutieres syndrome; however, RNASEH2B does not appear to be associated with a metabolic phenotype. Therefore this gene has been demoted to red.; to: Comment on list classification: Demoted from Amber to Red. RNASEH2B is associated with Aicardi-Goutieres syndrome 2 on OMIM and Gene2Phenotype. There are 2 unrelated cases on OMIM about RNASEH2B causing Aicardi-Goutieres syndrome; however, RNASEH2B does not appear to be associated with a metabolic phenotype. Therefore this gene has been demoted to red. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.305 | RNASEH2C | Ivone Leong Classified gene: RNASEH2C as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.305 | RNASEH2C | Ivone Leong Added comment: Comment on list classification: Demoted from Amber to Red. RNASEH2C is associated with Aicardi-Goutieres syndrome 3 on OMIM and Gene2Phenotype. There are 2 unrelated cases from the same geographical region on OMIM about RNASEH2C causing Aicardi-Goutieres syndrome; however, RNASEH2C does not appear to be associated with a metabolic phenotype. Therefore this gene has been demoted to red. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.305 | RNASEH2C | Ivone Leong Gene: rnaseh2c has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.304 | RNASEH2B | Ivone Leong Classified gene: RNASEH2B as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.304 | RNASEH2B | Ivone Leong Added comment: Comment on list classification: Demoted from Amber to Red. RNASEH2B is associated with Aicardi-Goutieres syndrome 2 on OMIM and Gene2Phenotype. There are 2 unrelated cases on OMIM supporting the gene-disease link between RNASEH2B with Aicardi-Goutieres syndrome; however, RNASEH2B does not appear to be associated with a metabolic phenotype. Therefore this gene has been demoted to red. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.304 | RNASEH2B | Ivone Leong Gene: rnaseh2b has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.303 | RNASEH2A | Ivone Leong Classified gene: RNASEH2A as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.303 | RNASEH2A | Ivone Leong Gene: rnaseh2a has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.302 | HARS2 | Sarah Leigh Added comment: Comment on phenotypes: Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.302 | HARS2 | Sarah Leigh Phenotypes for gene: HARS2 were changed from Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); ?Perrault syndrome 2 614926 to ?Perrault syndrome 2 614926 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.301 | HARS2 | Sarah Leigh Added comment: Comment on publications: PMID: 21464306: One family reported, with five affected siblings who were compound heterozygous for variants L200V and V368L. Functional evidence in c.elegans was provided. PMID: 27650058: patients with sporadic Perrault syndrome IV-1 and VI-I were homozygous for the c.1010A>G (p.Tyr337Cys) variant. The patients were claimed not to be related, but originated from the same region in Morocco and the variant was characterised as being in the same haplotype, suggesting a founder effect. Found at a frequency of 1/121332 in Exac. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.300 | HARS2 | Sarah Leigh Classified gene: HARS2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.300 | HARS2 | Sarah Leigh Added comment: Comment on list classification: This gene was discussed on the NHSE GMS Mitochondrial Specialist Group Meeting call on 25th February 2019. It was confirmed that Perrault syndrome was relevant for this panel, and that there was enough evidence for the gene to be Green. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.300 | HARS2 | Sarah Leigh Gene: hars2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.299 | FECH | Sarah Leigh Added comment: Comment on phenotypes: Erythropoietic protoporphyria (Porphyrias with acute painful photosensitivity);Erythropoietic protoporphyria, mild variant | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.299 | FECH | Sarah Leigh Phenotypes for gene: FECH were changed from Erythropoietic protoporphyria (Porphyrias with acute painful photosensitivity); Erythropoietic protoporphyria, mild variant to Protoporphyria, erythropoietic, 1 177000 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.298 | FECH | Sarah Leigh Classified gene: FECH as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.298 | FECH | Sarah Leigh Added comment: Comment on list classification: Associated with phenotype in OMIM and not in Gen2Phen. At least 16 variants identified in unrelated cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.298 | FECH | Sarah Leigh Gene: fech has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.297 | DHODH | Sarah Leigh Added comment: Comment on phenotypes: Dihydroorotate dehydrogenase deficiency (Disorders of pyrimidine metabolism);Bilateral microtia;Deafness and congenital structural abnormalities;Unexplained skeletal dysplasia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.297 | DHODH | Sarah Leigh Phenotypes for gene: DHODH were changed from Dihydroorotate dehydrogenase deficiency (Disorders of pyrimidine metabolism); Bilateral microtia; Deafness and congenital structural abnormalities; Unexplained skeletal dysplasia to Miller syndrome 263750 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.295 | DHODH | Sarah Leigh Classified gene: DHODH as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.295 | DHODH | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 11 variants reported in 6 families (PMID 19915526), together with a knockout mouse model (PMID 27626380). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.295 | DHODH | Sarah Leigh Gene: dhodh has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.294 | DHCR24 | Sarah Leigh Added comment: Comment on phenotypes: Desmosterolosis (Disorders of sterol biosynthesis);Intellectual disability;Unexplained skeletal dysplasia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.294 | DHCR24 | Sarah Leigh Phenotypes for gene: DHCR24 were changed from Desmosterolosis (Disorders of sterol biosynthesis); Intellectual disability; Unexplained skeletal dysplasia to Desmosterolosis 602398 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.292 | DHCR24 | Sarah Leigh Classified gene: DHCR24 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.292 | DHCR24 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 7 variants reported in at least cases, two of the variants were in cis in a case which was compound heterozygous with another variant (PMID 11519011). Supportive functional studies were also presented. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.292 | DHCR24 | Sarah Leigh Gene: dhcr24 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.289 | DCXR | Sarah Leigh Classified gene: DCXR as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.289 | DCXR | Sarah Leigh Added comment: Comment on list classification: Associated with phenotype in OMIM and not in Gen2Phen. At least 2 variants identified within Ashkenazi Jewish population, that functional studies have shown to be loss of function variants that result in lack of the normal DCXR protein. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.289 | DCXR | Sarah Leigh Gene: dcxr has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.288 | DCXR | Sarah Leigh Classified gene: DCXR as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.288 | DCXR | Sarah Leigh Gene: dcxr has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.286 | CYP7B1 | Sarah Leigh Classified gene: CYP7B1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.286 | CYP7B1 | Sarah Leigh Added comment: Comment on list classification: At least 10 variants identified in unrelated cases of Spastic paraplegia 5A, autosomal recessive 270800 and one of these variants was also found in 3 unrelated cases of Bile acid synthesis defect, congenital, 3 613812, which is a more relevant phenotype for metabolic panels. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.286 | CYP7B1 | Sarah Leigh Gene: cyp7b1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.284 | PTS | Ivone Leong Classified gene: PTS as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.284 | PTS | Ivone Leong Added comment: Comment on list classification: Promoted from Amber to Green. PTS is associated with an appropriate phenotype on OMIM and Gene2Phenotype. There are >3 unrelated cases listed on OMIM. Therefore, enough evidence for this gene to be promoted to Green status. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.284 | PTS | Ivone Leong Gene: pts has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.283 | CYP7B1 | Sarah Leigh Classified gene: CYP7B1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.283 | CYP7B1 | Sarah Leigh Added comment: Comment on list classification: Associated with phenotype in OMIM and not in Gen2Phen. At least 10 variants identified in unrelated cases of Spastic paraplegia 5A, autosomal recessive 270800 and one of these variants was also found in a case of Bile acid synthesis defect, congenital, 3 613812. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.283 | CYP7B1 | Sarah Leigh Gene: cyp7b1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.280 | CTSC | Sarah Leigh Added comment: Comment on phenotypes: Other lysosomal disorders, Cathepsin-related disorders;Unexplained skeletal dysplasia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.280 | CTSC | Sarah Leigh Phenotypes for gene: CTSC were changed from Papillon-Lef vre syndrome (Other lysosomal disorders, Cathepsin-related disorders); Unexplained skeletal dysplasia to Haim-Munk syndrome 245010; Papillon-Lefevre syndrome 245000; Periodontitis 1, juvenile 170650 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.279 | CTSC | Sarah Leigh Classified gene: CTSC as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.279 | CTSC | Sarah Leigh Added comment: Comment on list classification: Associated with phenotype in OMIM and not in Gen2Phen. At least 13 variants identified in unrelated cases of Papillon-Lefevre syndrome 245000. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.279 | CTSC | Sarah Leigh Gene: ctsc has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.278 | CLDN19 | Sarah Leigh Added comment: Comment on phenotypes: Disorder of magnesium metabolism; Renal tract calcification (or Nephrolithiasis/nephrocalcinosis) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.278 | CLDN19 | Sarah Leigh Phenotypes for gene: CLDN19 were changed from Hypomagnesaemia type 5, renal with ocular involvement (Disorder of magnesium metabolism); Renal tract calcification (or Nephrolithiasis/nephrocalcinosis) to Hypomagnesemia 5, renal, with ocular involvement 248190 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.276 | CLDN19 | Sarah Leigh Classified gene: CLDN19 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.276 | CLDN19 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 5 variants reported in at least 6 unrelated cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.276 | CLDN19 | Sarah Leigh Gene: cldn19 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.275 | CLDN16 | Sarah Leigh Added comment: Comment on phenotypes: Disorder of magnesium metabolism; Renal tract calcification (or Nephrolithiasis/nephrocalcinosis) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.275 | CLDN16 | Sarah Leigh Phenotypes for gene: CLDN16 were changed from Hypomagnesaemia type 3, renal (Disorder of magnesium metabolism); Renal tract calcification (or Nephrolithiasis/nephrocalcinosis) to Hypomagnesemia 3, renal 248250 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.274 | CLDN16 | Sarah Leigh Classified gene: CLDN16 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.274 | CLDN16 | Sarah Leigh Added comment: Comment on list classification: Associated with phenotype in OMIM and not in Gen2Phen. At least 19 variants identified in unrelated cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.274 | CLDN16 | Sarah Leigh Gene: cldn16 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.271 | CISD2 | Sarah Leigh Classified gene: CISD2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.271 | CISD2 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as both RD and IF Gen2Phen gene. At least 3 variants reported in unrelated cases, together with segration and functional studies. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.271 | CISD2 | Sarah Leigh Gene: cisd2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.269 | APOB | Sarah Leigh Classified gene: APOB as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.269 | APOB | Sarah Leigh Added comment: Comment on list classification: Associated with phenotype in OMIM and not in Gen2Phen. At least 5 variants associated with Hypobetalipoproteinemia 615558 without other variants in other genes and 2 variants associated with Hypercholesterolemia, familial, 2 144010 in numberous cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.269 | APOB | Sarah Leigh Gene: apob has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.268 | ALPL | Sarah Leigh Added comment: Comment on phenotypes: Hypophosphatasia (Disorders of pyridoxine metabolism);Craniosynostosis syndromes phenotypes;Osteogenesis Imperfecta;Unexplained skeletal dysplasia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.268 | ALPL | Sarah Leigh Phenotypes for gene: ALPL were changed from Hypophosphatasia (Disorders of pyridoxine metabolism); Craniosynostosis syndromes phenotypes; Osteogenesis Imperfecta; Unexplained skeletal dysplasia to Hypophosphatasia, adult 146300; Hypophosphatasia, childhood 241510; Hypophosphatasia, infantile 241500; Odontohypophosphatasia 146300 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.266 | ALPL | Sarah Leigh Classified gene: ALPL as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.266 | ALPL | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 16 variants reported in hypophosphatasia, infantile 241500, some of these variants and others were found in childhood and adult Hypophosphatasia and two addtional variants were reported in a case of perinatal lethal hypophosphatasia (PMID 11745997). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.266 | ALPL | Sarah Leigh Gene: alpl has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.265 | IER3IP1 | Helen Brittain Gene: ier3ip1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.265 | IER3IP1 | Helen Brittain Classified gene: IER3IP1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.265 | IER3IP1 | Helen Brittain Gene: ier3ip1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.264 | ALDH3A2 | Sarah Leigh Classified gene: ALDH3A2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.264 | ALDH3A2 | Sarah Leigh Gene: aldh3a2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.263 | ALAS2 | Sarah Leigh Classified gene: ALAS2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.263 | ALAS2 | Sarah Leigh Gene: alas2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.262 | ADSL | Sarah Leigh Classified gene: ADSL as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.262 | ADSL | Sarah Leigh Gene: adsl has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.261 | ADA | Sarah Leigh Classified gene: ADA as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.261 | ADA | Sarah Leigh Gene: ada has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.260 | ACY1 | Sarah Leigh Classified gene: ACY1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.260 | ACY1 | Sarah Leigh Gene: acy1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.259 | ABHD12 | Sarah Leigh Classified gene: ABHD12 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.259 | ABHD12 | Sarah Leigh Gene: abhd12 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.258 | ABCG8 | Sarah Leigh Classified gene: ABCG8 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.258 | ABCG8 | Sarah Leigh Gene: abcg8 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.257 | ABCG5 | Sarah Leigh Classified gene: ABCG5 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.257 | ABCG5 | Sarah Leigh Gene: abcg5 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.256 | ALAS2 | Sarah Leigh edited their review of gene: ALAS2: Added comment: Associated with phenotype in OMIM and not in Gen2Phen. At least 18 variants identified in Anemia, sideroblastic, 1 300751 and two variants in Protoporphyria, erythropoietic, X-linked 300752 in six unrelated families, together with functional studies.; Changed rating: GREEN; Changed publications: 27604308, 1570328, 7560104, 12663458, 18760763; Changed phenotypes: Anemia, sideroblastic, 1 300751, Protoporphyria, erythropoietic, X-linked 300752 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.256 | ADA | Sarah Leigh edited their review of gene: ADA: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 30 variants reported associated with Adenosine deaminase deficiency.; Changed rating: GREEN; Changed publications: 27604308, 3684597, 2783588, 1680289; Changed phenotypes: Adenosine deaminase deficiency, partial 102700, Severe combined immunodeficiency due to ADA deficiency 102700, Combined B and T cell defect, SCID, Infantile enterocolitis & monogenic inflammatory bowel disease | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.256 | ABHD12 | Sarah Leigh edited their review of gene: ABHD12: Added comment: Associated with phenotype in OMIM and not in Gen2Phen. At least 7 variants identified in at least 6 unrelated cases; Changed rating: GREEN; Changed publications: 27604308, 20797687, 24697911 ; Changed phenotypes: Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract 612674, Hereditary ataxia, Posterior segment abnormalities, Congenital hearing impairment (profound/severe), PHARC syndrome (Disorders of complex lipid synthesis) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.256 | ABCG8 | Sarah Leigh edited their review of gene: ABCG8: Added comment: Associated with phenotype in OMIM and not in Gen2Phen. At least 9 variants identified in numberous unrelated cases; Changed rating: GREEN; Changed publications: 27604308, 11452359, 15996216, 11099417, 22981120; Changed phenotypes: Sitosterolemia 210250, Familial hypercholesterolaemia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.256 | ABCG5 | Sarah Leigh edited their review of gene: ABCG5: Added comment: Associated with phenotype in OMIM and not in Gen2Phen. At least 8 variants identified in unrelated cases; Changed rating: GREEN; Changed publications: 27604308, 11099417, 11138003, 20719861, 17976197; Changed phenotypes: Sitosterolemia 210250, Familial hypercholesterolaemia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.255 | PSPH | Sarah Leigh Phenotypes for gene: PSPH were changed from Phosphoserine phosphatase deficiency (Disorders of serine, glycine or glycerate metabolism); Intellectual disability; Unexplained skeletal dysplasia to Phosphoserine phosphatase deficiency 614023 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.254 | PSAT1 | Sarah Leigh Classified gene: PSAT1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.254 | PSAT1 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene for ?Phosphoserine aminotransferase deficiency 610992; Neu-Laxova syndrome 2 616038. At least 5 variants reported in 6 cases of Neu-Laxova syndrome 2 616038 and 2 variants in a case of ?Phosphoserine aminotransferase deficiency 610992. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.254 | PSAT1 | Sarah Leigh Gene: psat1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.252 | PSAT1 | Sarah Leigh Phenotypes for gene: PSAT1 were changed from Phosphoserine aminotransferase deficiency (Disorders of serine, glycine or glycerate metabolism); Unexplained skeletal dysplasia to ?Phosphoserine aminotransferase deficiency 610992; Neu-Laxova syndrome 2 616038 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.251 | PRPS1 | Sarah Leigh Classified gene: PRPS1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.251 | PRPS1 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for Arts syndrome 301835, Charcot-Marie-Tooth disease, X-linked recessive, 5 311070, Deafness, X-linked 1 304500 and Phosphoribosylpyrophosphate synthetase superactivity 300661. At least 22 variants have been reported across the phenotypes. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.251 | PRPS1 | Sarah Leigh Gene: prps1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.250 | PRPS1 | Sarah Leigh Phenotypes for gene: PRPS1 were changed from Phosphoribosyl pyrophosphate synthetase 1 defects (Disorders of purine metabolism); Charcot-Marie-Tooth disease; Congenital hearing impairment (profound/severe); Intellectual disability; Intellectual_disability to Arts syndrome 301835; Charcot-Marie-Tooth disease, X-linked recessive, 5 311070; Deafness, X-linked 1 304500; Gout, PRPS-related 300661; Phosphoribosylpyrophosphate synthetase superactivity 300661 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.247 | ATP5A1 | Sarah Leigh Classified gene: ATP5A1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.247 | ATP5A1 | Sarah Leigh Added comment: Comment on list classification: Two variants together with functional studies. The Amber rating is based on the views of Anna de Burca (Genomics England Clinical Fellow) that the interpretation of PMID 23599390 that the boys have inherited a heterozygous variant from their father while not expressing the maternal allele due to unknown variant affecting expression. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.247 | ATP5A1 | Sarah Leigh Gene: atp5a1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.245 | POR | Sarah Leigh Classified gene: POR as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.245 | POR | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 10 variants associated with Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis 201750 and 6 variants associated with Disordered steroidogenesis due to cytochrome P450 oxidoreductase 613571. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.245 | POR | Sarah Leigh Gene: por has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.244 | POR | Sarah Leigh Phenotypes for gene: POR were changed from Antley-Bixler syndrome with disordered steroidogenesis; Craniosynostosis syndromes phenotypes; Disorders of sex development; Unexplained skeletal dysplasia to Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis 201750; Disordered steroidogenesis due to cytochrome P450 oxidoreductase 613571 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.242 | PNP | Sarah Leigh Classified gene: PNP as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.242 | PNP | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 10 variants reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.242 | PNP | Sarah Leigh Gene: pnp has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.241 | PNP | Sarah Leigh Added comment: Comment on phenotypes: Purine nucleoside phosphorylase deficiency (Disorders of purine metabolism);SCID | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.241 | PNP | Sarah Leigh Phenotypes for gene: PNP were changed from Purine nucleoside phosphorylase deficiency (Disorders of purine metabolism); SCID to Immunodeficiency due to purine nucleoside phosphorylase deficiency 613179 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.240 | PINK1 | Sarah Leigh Classified gene: PINK1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.240 | PINK1 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 12 variants were reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.240 | PINK1 | Sarah Leigh Gene: pink1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.237 | PIGM | Sarah Leigh Classified gene: PIGM as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.237 | PIGM | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. At least 1 variant was reported in 2 unrelated families (PMID 16767100), together with supportive functional studies (PMID 17442906 & 25293775). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.237 | PIGM | Sarah Leigh Gene: pigm has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.235 | PIGM | Sarah Leigh Added comment: Comment on phenotypes: Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation;Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.235 | PIGM | Sarah Leigh Phenotypes for gene: PIGM were changed from Phosphatidylinositolglycan, class M deficiency (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation); Glycosylphosphatidylinositol deficiency 610293 to Glycosylphosphatidylinositol deficiency 610293 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.233 | PHGDH | Sarah Leigh Classified gene: PHGDH as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.233 | PHGDH | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for both phenotypes. At least 6 variants reported in 6 unrelated cases of Phosphoglycerate dehydrogenase deficiency 601815 and 4 variants reported in 4 unrelated cases of Neu-Laxova syndrome 1 256520. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.233 | PHGDH | Sarah Leigh Gene: phgdh has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.232 | PHGDH | Sarah Leigh Phenotypes for gene: PHGDH were changed from Phosphoglycerate dehydrogenase deficiency (Disorders of serine, glycine or glycerate metabolism); Intellectual disability; Unexplained skeletal dysplasia to Neu-Laxova syndrome 1 256520; Phosphoglycerate dehydrogenase deficiency 601815 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.230 | PEPD | Sarah Leigh Classified gene: PEPD as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.230 | PEPD | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 11 variants reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.230 | PEPD | Sarah Leigh Gene: pepd has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.228 | PDPR | Sarah Leigh Classified gene: PDPR as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.228 | PDPR | Sarah Leigh Added comment: Comment on list classification: Not associated with a phenotype in OMIM or in Gen2Phen. At least 1 variant reported in a case of global developmental delay, typical Joubert syndrome, according to PMID 25558065. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.228 | PDPR | Sarah Leigh Gene: pdpr has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.227 | PCSK9 | Sarah Leigh Added comment: Comment on mode of pathogenicity: Gain of function variants are responsible for Hypercholesterolemia, familial, 3 603776, while loss of function variants are responsible for {Low density lipoprotein cholesterol level QTL 1} 603776. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.226 | PCSK9 | Sarah Leigh Classified gene: PCSK9 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.226 | PCSK9 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 gain of function variants reported in unrelated cases of Hypercholesterolemia, familial, 3 603776 and at least 5 loss of function variants have been reported in unrelated cases of {Low density lipoprotein cholesterol level QTL 1} 603776. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.226 | PCSK9 | Sarah Leigh Gene: pcsk9 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.224 | PCSK9 | Sarah Leigh Phenotypes for gene: PCSK9 were changed from Autosomal dominant hypercholesterolemia-3 (Inherited hypercholesterolaemias); Familial hypercholesterolaemia to Hypercholesterolemia, familial, 3 603776; {Low density lipoprotein cholesterol level QTL 1} 603776 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.223 | PCK1 | Sarah Leigh Classified gene: PCK1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.223 | PCK1 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in unrelated cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.223 | PCK1 | Sarah Leigh Gene: pck1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.221 | PCK1 | Sarah Leigh Added comment: Comment on phenotypes: Phosphoenolpyruvate carboxykinase deficiency (Disorders of gluconeogenesis);Cytosolic phosphoenolpyruvate carboxykinase (PEPCK)) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.221 | PCK1 | Sarah Leigh Phenotypes for gene: PCK1 were changed from Phosphoenolpyruvate carboxykinase deficiency (Disorders of gluconeogenesis); ?Phosphoenolpyruvate carboxykinase-1, cytosolic, deficiency; (PCK1 DEFICIENCY, Cytosolic phosphoenolpyruvate carboxykinase (PEPCK)) to ?Phosphoenolpyruvate carboxykinase deficiency, cytosolic 261680 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.218 | PANK2 | Sarah Leigh Classified gene: PANK2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.218 | PANK2 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 13 variants reported for Neurodegeneration with brain iron accumulation 234200 and 3 variants in 2 unrelated cases of HARP syndrome 607236. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.218 | PANK2 | Sarah Leigh Gene: pank2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.216 | OPLAH | Sarah Leigh Classified gene: OPLAH as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.216 | OPLAH | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants have been reported. It is not clear whether the mode of inheritance is biallelic or monoallelic as homozygous and heterozygote cases have been seen. The PMID 21651516 reports two sibs who are homozygous for a terminating variant, the younger brother is 5-oxoprolinase deficiency, however, his clinically unaffected sister just has increased 5-oxoproline excretion. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.216 | OPLAH | Sarah Leigh Gene: oplah has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.213 | OCRL | Sarah Leigh Classified gene: OCRL as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.213 | OCRL | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for both Dent disease 2 300555 and Lowe syndrome 309000. At least 5variants reported in Dent disease 2 300555 and 4 variants in Lowe syndrome 309000. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.213 | OCRL | Sarah Leigh Gene: ocrl has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.212 | OCRL | Sarah Leigh Added comment: Comment on phenotypes: Lowe syndrome (Disorders of amino acid transport);Cataracts;Intellectual disability;Intellectual_disability;Renal tract calcification (or Nephrolithiasis/nephrocalcinosis) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.212 | OCRL | Sarah Leigh Phenotypes for gene: OCRL were changed from Lowe syndrome (Disorders of amino acid transport); Cataracts; Intellectual disability; Intellectual_disability; Renal tract calcification (or Nephrolithiasis/nephrocalcinosis) to Dent disease 2 300555; Lowe syndrome 309000 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.210 | NDUFB9 | Sarah Leigh Classified gene: NDUFB9 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.210 | NDUFB9 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 1 variant reported, together with supportive functional studies. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.210 | NDUFB9 | Sarah Leigh Gene: ndufb9 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.206 | MVK | Sarah Leigh changed review comment from: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 8 variants reported in Hyper-IgD syndrome 260920, 9 variants reported in Mevalonic aciduria 610377 and 8 variants reported in Porokeratosis 3, multiple types 175900.; to: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. Numerous variants reported for each phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.205 | MVK | Sarah Leigh Classified gene: MVK as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.205 | MVK | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 8 variants reported in Hyper-IgD syndrome 260920, 9 variants reported in Mevalonic aciduria 610377 and 8 variants reported in Porokeratosis 3, multiple types 175900. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.205 | MVK | Sarah Leigh Gene: mvk has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.204 | MVK | Sarah Leigh Added comment: Comment on phenotypes: Mevalonate kinase deficiency (Disorders of sterol biosynthesis);Infantile enterocolitis & monogenic inflammatory bowel disease | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.204 | MVK | Sarah Leigh Phenotypes for gene: MVK were changed from Mevalonate kinase deficiency (Disorders of sterol biosynthesis); Infantile enterocolitis & monogenic inflammatory bowel disease to Hyper-IgD syndrome 260920; Mevalonic aciduria 610377; Porokeratosis 3, multiple types 175900 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.203 | MTPAP | Sarah Leigh Added comment: Comment on phenotypes: Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.203 | MTPAP | Sarah Leigh Phenotypes for gene: MTPAP were changed from Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only); ?Spastic ataxia 4, autosomal recessive, 613672 to ?Spastic ataxia 4, autosomal recessive, 613672 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.201 | MTPAP | Sarah Leigh Classified gene: MTPAP as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.201 | MTPAP | Sarah Leigh Added comment: Comment on list classification: Associated with phenotype in OMIM and not in Gen2Phen. At least 2 variants identified in unrelated cases, and supportive functional studies. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.201 | MTPAP | Sarah Leigh Gene: mtpap has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.200 | MTFMT | Sarah Leigh Classified gene: MTFMT as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.200 | MTFMT | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 8 variants reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.200 | MTFMT | Sarah Leigh Gene: mtfmt has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.198 | MTFMT | Sarah Leigh Added comment: Comment on phenotypes: Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.198 | MTFMT | Sarah Leigh Phenotypes for gene: MTFMT were changed from Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Inherited white matter disorders to Combined oxidative phosphorylation deficiency 15 614947; Mitochondrial complex I deficiency, nuclear type 27 618248 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.197 | MRPL3 | Sarah Leigh Classified gene: MRPL3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.197 | MRPL3 | Sarah Leigh Added comment: Comment on list classification: This gene was rated as Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: 2 unrelated families (4 sibs + 1 unrelated case) and functional studies. From panel: Possible mitochondrial disorder - nuclear genes (Version 0.187). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.197 | MRPL3 | Sarah Leigh Gene: mrpl3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.195 | MRPL3 | Sarah Leigh Added comment: Comment on phenotypes: Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.195 | MRPL3 | Sarah Leigh Phenotypes for gene: MRPL3 were changed from Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Combined oxidative phosphorylation deficiency 9, 614582 to Combined oxidative phosphorylation deficiency 9, 614582 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.194 | MOCS2 | Sarah Leigh Classified gene: MOCS2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.194 | MOCS2 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 9 variants reported in at least 8 unrelated cases, together with supportive functional studies. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.194 | MOCS2 | Sarah Leigh Gene: mocs2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.191 | MOCS1 | Sarah Leigh Classified gene: MOCS1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.191 | MOCS1 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 5 variants reported unrelated cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.191 | MOCS1 | Sarah Leigh Gene: mocs1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.187 | MAOA | Sarah Leigh Classified gene: MAOA as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.187 | MAOA | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 4 variants reported in unrelated cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.187 | MAOA | Sarah Leigh Gene: maoa has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.185 | MAGT1 | Sarah Leigh Classified gene: MAGT1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.185 | MAGT1 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. At least 3 variants reported in unrelated cases, together with mouse knock-out model (PMID 29581357). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.185 | MAGT1 | Sarah Leigh Gene: magt1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.184 | MAGT1 | Sarah Leigh Phenotypes for gene: MAGT1 were changed from IAP-CDG (Disorders of protein N-glycosylation); Combined B and T cell defect to Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia 300853 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.183 | LIPC | Sarah Leigh Classified gene: LIPC as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.183 | LIPC | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in two unrelated families with Hepatic lipase deficiency, 614025. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.183 | LIPC | Sarah Leigh Gene: lipc has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.182 | LIPC | Sarah Leigh Classified gene: LIPC as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.182 | LIPC |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in two unrelated families with Hepatic lipase deficiency, 614025. |
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Undiagnosed metabolic disorders v1.182 | LIPC | Sarah Leigh Gene: lipc has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.180 | LIPC | Sarah Leigh Phenotypes for gene: LIPC were changed from {Diabetes mellitus, noninsulin-dependent} 125853; Hepatic lipase deficiency 614025; [High density lipoprotein cholesterol level QTL 12] 612797 to Hepatic lipase deficiency, 614025; [High density lipoprotein cholesterol level QTL 12] 612797; {Diabetes mellitus, noninsulin-dependent} 125853 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.178 | LIPC | Sarah Leigh Phenotypes for gene: LIPC were changed from Hepatic lipase deficiency (Inherited mixed hyperlipidaemias); Hepatic lipase deficiency, 614025; [High density lipoprotein cholesterol level QTL 12] 612797; {Diabetes mellitus, noninsulin-dependent} 125853 to {Diabetes mellitus, noninsulin-dependent} 125853; Hepatic lipase deficiency 614025; [High density lipoprotein cholesterol level QTL 12] 612797 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.177 | LDLRAP1 | Sarah Leigh Classified gene: LDLRAP1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.177 | LDLRAP1 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 11 variants reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.177 | LDLRAP1 | Sarah Leigh Gene: ldlrap1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.175 | LDLRAP1 | Sarah Leigh Added comment: Comment on phenotypes: Autosomal recessive hypercholesterolemia (Inherited hypercholesterolaemias);Familial hypercholesterolaemia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.175 | LDLRAP1 | Sarah Leigh Phenotypes for gene: LDLRAP1 were changed from Autosomal recessive hypercholesterolemia (Inherited hypercholesterolaemias); Familial hypercholesterolaemia to Hypercholesterolemia, familial, 4 603813 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.173 | LDLR | Sarah Leigh Classified gene: LDLR as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.173 | LDLR | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. Over 2000 variants reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.173 | LDLR | Sarah Leigh Gene: ldlr has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.171 | LDLR | Sarah Leigh Added comment: Comment on phenotypes: Disorder of low density lipoprotein receptor (Inherited hypercholesterolaemias);Familial hypercholesterolaemia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.171 | LDLR | Sarah Leigh Phenotypes for gene: LDLR were changed from Disorder of low density lipoprotein receptor (Inherited hypercholesterolaemias); Familial hypercholesterolaemia to Hypercholesterolemia, familial, 1 143890; LDL cholesterol level QTL2 143890 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.169 | LBR | Sarah Leigh Classified gene: LBR as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.169 | LBR | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for Greenberg skeletal dysplasia 215140. At least 15 variants have been reported, in 5 unrelated cases of Pelger-Huet anomaly 169400, 3 unrelated cases of Pelger-Huet anomaly with mild skeletal anomalies 618019, 5 unrelated cases of Greenberg skeletal dysplasia 215140 and in a single case of ?Reynolds syndrome 613471. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.169 | LBR | Sarah Leigh Gene: lbr has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.168 | LBR | Sarah Leigh Added comment: Comment on phenotypes: Greenberg skeletal dysplasia (Disorders of sterol biosynthesis);Fetal hydrops;Unexplained skeletal dysplasia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.168 | LBR | Sarah Leigh Phenotypes for gene: LBR were changed from Greenberg skeletal dysplasia (Disorders of sterol biosynthesis); Fetal hydrops; Unexplained skeletal dysplasia to ?Reynolds syndrome 613471; Greenberg skeletal dysplasia 215140; Pelger-Huet anomaly 169400; Pelger-Huet anomaly with mild skeletal anomalies 618019 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.167 | ISCU | Sarah Leigh Classified gene: ISCU as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.167 | ISCU | Sarah Leigh Added comment: 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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.167 | ISCU | Sarah Leigh Gene: iscu has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.165 | HSD17B10 | Sarah Leigh Classified gene: HSD17B10 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.165 | HSD17B10 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for 2-methyl-3-hydroxybutyrylL-coA dehydrogenase deficiency and for mental retardation syndromic X-linked type 10 . At least 8 variants reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.165 | HSD17B10 | Sarah Leigh Gene: hsd17b10 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.161 | HPS1 | Sarah Leigh Classified gene: HPS1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.161 | HPS1 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 7 variants reported in at least 5 unrelated cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.161 | HPS1 | Sarah Leigh Gene: hps1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.158 | HPD | Sarah Leigh Classified gene: HPD as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.158 | HPD | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene for both phenotypes. At least 4 variants reported in unrelated cases of Tyrosinemia, type III 276710 and 4 variants in 6 unrelated cases of Hawkinsinuria 140350 (at least 2 of these cases were compound heterozygotes). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.158 | HPD | Sarah Leigh Gene: hpd has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.156 | HPD | Sarah Leigh Added comment: Comment on phenotypes: 4-hydroxyphenylpyruvate dioxygenase deficiency (Disorders of phenylalanine or tyrosine metabolism);Intellectual disability | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.156 | HPD | Sarah Leigh Phenotypes for gene: HPD were changed from 4-hydroxyphenylpyruvate dioxygenase deficiency (Disorders of phenylalanine or tyrosine metabolism); Intellectual disability to Hawkinsinuria 140350; Tyrosinemia, type III 276710 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.155 | HADH | Sarah Leigh Classified gene: HADH as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.155 | HADH | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. Numerous variants reported in unrelated cases of Hyperinsulinemic hypoglycemia, familial, 4 609975. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.155 | HADH | Sarah Leigh Gene: hadh has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.152 | GNMT | Sarah Leigh Classified gene: GNMT as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.152 | GNMT | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 3 variants reported in 2 unrelated cases, with supportive functional data. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.152 | GNMT | Sarah Leigh Gene: gnmt has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.150 | GLUL | Sarah Leigh Classified gene: GLUL as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.150 | GLUL |
Sarah Leigh Added comment: Comment on list classification: This gene was part of an initial gene list collated by Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group. Additional information was not provided, such as mode of inheritance and phenotype. Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 3 variants reported in unrelated cases. |
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Undiagnosed metabolic disorders v1.150 | GLUL | Sarah Leigh Gene: glul has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.147 | GK | Sarah Leigh Classified gene: GK as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.147 | GK | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 8 variants reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.147 | GK | Sarah Leigh Gene: gk has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.145 | GK | Sarah Leigh Classified gene: GK as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.145 | GK | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 8 variants reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.145 | GK | Sarah Leigh Gene: gk has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.140 | GAMT | Sarah Leigh Classified gene: GAMT as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.140 | GAMT | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 5 variants reported in 4 unrelated cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.140 | GAMT | Sarah Leigh Gene: gamt has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.138 | FTCD | Sarah Leigh Classified gene: FTCD as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.138 | FTCD | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 15 variants reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.138 | FTCD | Sarah Leigh Gene: ftcd has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.136 | FGFR2 | Sarah Leigh Classified gene: FGFR2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.136 | FGFR2 | Sarah Leigh Added comment: Comment on list classification: Associated with 14 phenotypes in OMIM and as confirmed Gen2Phen gene for acrocephalosyndactyly type V, Antley-Bixler syndrome, Apert syndrome, Beare-Stevenson cutis gyrata syndrome, Crouzon syndrome, familial scaphocephaly syndrome, Jackson-Weiss syndrome, lacrimo-auriculo-dento-digital syndrome. At least 44 variants reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.136 | FGFR2 | Sarah Leigh Gene: fgfr2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.135 | FGFR2 | Sarah Leigh Phenotypes for gene: FGFR2 were changed from Antley-Bixler syndrome type without disordered steroidogenesis; Arthrogryposis; Bilateral microtia; Choanal atresia; Craniosynostosis syndromes phenotypes; Deafness and congenital structural abnormalities; Unexplained skeletal dysplasia to Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis 207410; Apert syndrome 101200; Beare-Stevenson cutis gyrata syndrome 123790; Bent bone dysplasia syndrome 614592; Craniofacial-skeletal-dermatologic dysplasia 101600; Craniosynostosis, nonspecific; Crouzon syndrome 123500; Gastric cancer, somatic 613659; Jackson-Weiss syndrome 123150; LADD syndrome 149730; Pfeiffer syndrome 101600; Saethre-Chotzen syndrome 101400; Scaphocephaly and Axenfeld-Rieger anomaly; Scaphocephaly, maxillary retrusion, and mental retardation 609579 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.132 | DPM3 | Sarah Leigh Classified gene: DPM3 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.132 | DPM3 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 2 variants reported as homozygotes in two unrelated cases, together with segregation and supportive functional studies. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.132 | DPM3 | Sarah Leigh Gene: dpm3 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.131 | DHDDS | Sarah Leigh changed review comment from: Amber review assigned as this gene is Green on the V1 panel(s) named as a phenotype(s); to: Amber review assigned as this gene is Green on the V1 panel(s) named as a phenotype(s) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.131 | TANGO2 | Sarah Leigh Classified gene: TANGO2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.131 | TANGO2 | Sarah Leigh Added comment: Comment on list classification: Based on recommendations of Helen Britain (Clinical Fellow, Genomics England) as cases will have of periods of decompensation that are associated with hypoglycaemia and hyperammonaemia. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.131 | TANGO2 | Sarah Leigh Gene: tango2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.130 | TANGO2 |
Sarah Leigh gene: TANGO2 was added gene: TANGO2 was added to Undiagnosed metabolic disorders. Sources: Other Mode of inheritance for gene: TANGO2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TANGO2 were set to Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration 616878 Review for gene: TANGO2 was set to GREEN Added comment: Sources: Other |
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Undiagnosed metabolic disorders v1.129 | STAT2 | Sarah Leigh Classified gene: STAT2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.129 | STAT2 | Sarah Leigh Added comment: Comment on list classification: Based on recommendation of Helen Britain (Clinical Fellow, Genomics England), that the majority of cases will be presenting in the context of overwhelming infection. The raised lactate and encephalomyopathy are potentially relevant phenotypes for this panel, however more evidence is needed on how common this presentation is, and whether it is always clearly associated with a proven infection. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.129 | STAT2 | Sarah Leigh Gene: stat2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.127 | IER3IP1 | Sarah Leigh Classified gene: IER3IP1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.127 | IER3IP1 | Sarah Leigh Added comment: Comment on list classification: Based on recommendation of Helen Britain (Clinical Fellow, Genomics England), that patients will present with features of microcephaly / neonatal diabetes / developmental delay, rather than metabolic disorder. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.127 | IER3IP1 | Sarah Leigh Gene: ier3ip1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.124 | POLG2 | Sarah Leigh Added comment: Comment on mode of inheritance: Reporting and characterization of a homozygous POLG2 variant in mitochondrial DNA depletion syndrome and in an autosomal recessive epilepsy family without ophthalmoplegia (PMID 27592148; 30157269; 31286721). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.123 | FXN | Sarah Leigh Phenotypes for gene: FXN were changed from Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Hereditary ataxia to Friedreich ataxia, 229300; Friedreich ataxia with retained reflexes, 229300; Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.122 | FXN | Sarah Leigh Classified gene: FXN as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.122 | FXN |
Sarah Leigh Added comment: Comment on list classification: Associated with phenotype in OMIM and not in Gen2Phen. At least 9 variants identified in unrelated cases. FXN is rated Red on the mitochondrial panels on the recommendation of the GMS mitochondrial specialist test group, including by Carl Fratter (Oxford University Hospitals NHS Trust). As it is associated with Friedreich’s ataxia, which is technically a mitochondrial disorder, but the phenotype is different to other mitochondrial conditions. |
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Undiagnosed metabolic disorders v1.122 | FXN | Sarah Leigh Gene: fxn has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.121 | RANBP2 | Sarah Leigh Classified gene: RANBP2 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.121 | RANBP2 | Sarah Leigh Added comment: Comment on list classification: Demoted RANBP2 from Green to Amber following review by Zornitza Stark and agreement from Helen Brittain (Genomics England clinical team). Recent papers report patients with symptoms (including seizures) after a viral illness (PMID:30796099, PMID:28336122, PMID:25128471). However, listed as a susceptibility locus in OMIM, and papers report incomplete penetrance: variant present in asymptomatic maternal grandmother in PMID:30796099 and in the father in PMID:28336122. Therefore further information (e.g. on penetrance) is required for a clear gene:disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.121 | RANBP2 | Sarah Leigh Gene: ranbp2 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.120 | PGAM2 | Sarah Leigh changed review comment from: Comment on list classification: Additional case with biallelic variant and rhabdomyolysis; to: Comment on list classification: Associated with phenotype in OMIM and not in Gen2Phen. At least 4 variants identified in 3 unrelated cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.120 | DHCR7 | Sarah Leigh Classified gene: DHCR7 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.120 | DHCR7 | Sarah Leigh Added comment: Comment on list classification: Associated with phenotype in OMIM and as confirmed Gen2Phen gene. At least 21 variants reported. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.120 | DHCR7 | Sarah Leigh Gene: dhcr7 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.118 | FUT8 | Louise Daugherty Classified gene: FUT8 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.118 | FUT8 | Louise Daugherty Gene: fut8 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.116 | HYAL1 | Sarah Leigh Phenotypes for gene: HYAL1 were changed from MPS IX, Natowicz (MPS IV, Morquio disease); ?Mucopolysaccharidosis type IX, 601492 to ?Mucopolysaccharidosis type IX, 601492 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.114 | ARSG | Sarah Leigh changed review comment from: Candidate gene for neuronal ceroid lipofuscinosis as reported in dogs and mice models (PubMed: 20679209, 22689975, 25452429, 26975023) and in a ; to: Candidate gene for neuronal ceroid lipofuscinosis as reported in dogs and mice models (PubMed: 20679209, 22689975, 25452429, 26975023) and in 5 affected members of 3 consanguineous Yemenite Jewish families (PMID 29300381). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.112 | ARSG | Sarah Leigh changed review comment from: Candidate gene for neuronal ceroid lipofuscinosis as reported in dogs and mice; to: Candidate gene for neuronal ceroid lipofuscinosis as reported in dogs and mice models (PubMed: 20679209, 22689975, 25452429, 26975023) and in a | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.112 | ARSG | Sarah Leigh Added comment: Comment on phenotypes: Including neuronal ceroid lipofuscinosis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.112 | ARSG | Sarah Leigh Phenotypes for gene: ARSG were changed from neuronal ceroid lipofuscinosis to Usher syndrome, type IV 618144 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.106 | UQCRQ | Sarah Leigh Classified gene: UQCRQ as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.106 | UQCRQ | Sarah Leigh Added comment: Comment on list classification: Amber review collated by Carl Fratter (May 2019) on behalf of GMS mitochondrial specialist test group: One variant reported in a consanguineous Israeli Bedouin kindred with Mitochondrial complex III deficiency, nuclear type 4 (615159)(PMID: 18439546). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.106 | UQCRQ | Sarah Leigh Gene: uqcrq has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.104 | MANBA | Sarah Leigh Classified gene: MANBA as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.104 | MANBA | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 9 variants reported in 6 unrelated cases. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.104 | MANBA | Sarah Leigh Gene: manba has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.103 | ASAH1 | Sarah Leigh Phenotypes for gene: ASAH1 were changed from Farber disease (Sphingolipidoses); Fetal hydrops; Intellectual disability to Spinal muscular atrophy with progressive myoclonic epilepsy 159950; Farber lipogranulomatosis 228000; Fetal hydrops; Intellectual disability | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.102 | ASAH1 | Sarah Leigh Classified gene: ASAH1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.102 | ASAH1 | Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 7 variants reported in 6 cases of Farber lipogranulomatosis 228000 and 5 variants in 3 cases of Spinal muscular atrophy with progressive myoclonic epilepsy 159950. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.102 | ASAH1 | Sarah Leigh Gene: asah1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.98 | PGAM2 | Sarah Leigh Classified gene: PGAM2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.98 | PGAM2 | Sarah Leigh Added comment: Comment on list classification: Additional case with biallelic variant and rhabdomyolysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.98 | PGAM2 | Sarah Leigh Gene: pgam2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.95 | ATAD3A | Ivone Leong Classified gene: ATAD3A as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.95 | ATAD3A |
Ivone Leong Added comment: Comment on list classification: New gene added by external expert and reviewed by curation team and the clinical team: Sufficient evidence has been provided by the external expert review for this gene to be rated green. Other aspects of the phenotype may warrant for this gene to be included on alternative specific panels (i.e. intellectual disability); however, not enough evidence is available at the moment. Therefore, this gene has also been added to the "watchlist" so that more cases can be collected. |
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Undiagnosed metabolic disorders v1.95 | ATAD3A | Ivone Leong Gene: atad3a has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.92 | SLC35A1 | Rebecca Foulger Classified gene: SLC35A1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.92 | SLC35A1 | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Green as agreed with Helen Brittain following review of 2018 paper (PMID:30115659) and promotion to Green on the 'Congenital disorders of glycosylation' panel. In addition to the 'leaky' polymorphism reported in PMID:15576474, there are 3 cases (PMIDs 23873973, 28856833, 30115659) to support causation of glycosylation disorder. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.92 | SLC35A1 | Rebecca Foulger Gene: slc35a1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.90 | ATAD3A |
Julia Baptista gene: ATAD3A was added gene: ATAD3A was added to Undiagnosed metabolic disorders. Sources: Literature Mode of inheritance for gene: ATAD3A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: ATAD3A were set to 27640307 Phenotypes for gene: ATAD3A were set to Lactic acidosis; Methylglutaconic aciduria; Neurological abnormalities; Cerebellar hypoplasia; Optic atrophy; Hypertrophic cardiomyopathy; Scoliosis; Spinal muscular atrophy Review for gene: ATAD3A was set to GREEN gene: ATAD3A was marked as current diagnostic Added comment: A raised plasma lactate was reported in 4/7 families and methylglutaconic aciduria in 3/7 families (PMID: 27640307). Multiple patients with a diagnosis are described as having "severe metabolic disease". Sources: Literature |
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Undiagnosed metabolic disorders v1.90 | RRM2B | Rebecca Foulger Phenotypes for gene: RRM2B were changed from Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Mitochondrial Ribonucelotide Reductase subunit 2 deficiency (Disorders of purine metabolism); Disorders of mitochondrial DNA maintenance and integrity; Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy), 612075; Progressive external ophthalmoplegia with mitochondrial DNA deletions (autosomal dominant); 5,613077Mitochondrial DNA depletion syndrome 8B (MNGIE type), 612075; Mitochondrial DNA Depletion Syndrome (recessive) to Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Mitochondrial Ribonucelotide Reductase subunit 2 deficiency (Disorders of purine metabolism); Disorders of mitochondrial DNA maintenance and integrity; Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy), 612075; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5, 613077; Mitochondrial DNA depletion syndrome 8B (MNGIE type), 612075; Mitochondrial DNA Depletion Syndrome (recessive) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.88 | TWNK | Rebecca Foulger Phenotypes for gene: TWNK were changed from Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) ; Disorders of mitochondrial DNA maintenance and integrity; Progressive external ophthalmoplegia, autosomal dominant, 3, 609286Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), 271245; Mitochondrial DNA Depletion Syndrome; Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions (monoallelic); Mitochondrial Membrane Protein-Associated Neurodegeneration (biallelic); Mitochondrial DNA Depletion Syndrome (biallelic) to Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of mitochondrial DNA maintenance and integrity; Progressive external ophthalmoplegia, autosomal dominant, 3, 609286; Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), 271245; Mitochondrial DNA Depletion Syndrome; Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions (monoallelic); Mitochondrial Membrane Protein-Associated Neurodegeneration (biallelic); Mitochondrial DNA Depletion Syndrome (biallelic) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.87 | SLC25A4 | Rebecca Foulger Phenotypes for gene: SLC25A4 were changed from Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of mitochondrial DNA maintenance and integrity; Disorders of mitochondrial protein transport; Progressive external ophthalmoplegia with mitochondrial DNA deletions 3, 609283Mitochondrial DNA depletion syndrome 12 (cardiomyopathic type), 615418; Progressive External Ophthalmoplegia with Mitochondrial DNADeletions to Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of mitochondrial DNA maintenance and integrity; Disorders of mitochondrial protein transport; Progressive external ophthalmoplegia with mitochondrial DNA deletions 3, 609283; Mitochondrial DNA depletion syndrome 12 (cardiomyopathic type), 615418; Progressive External Ophthalmoplegia with Mitochondrial DNADeletions | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.83 | GLRA1 | Louise Daugherty Phenotypes for gene: GLRA1 were changed from Hyperekplexia, hereditary 1, autosomal dominant or recessive 149400 to Hyperekplexia, hereditary 1, 149400 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.82 | RPIA |
Sarah Leigh commented on gene: RPIA: Review by Konstantinos Varvagiannis for the Genetic Epilepsy syndromes panel. 9 Dec 2018, 1:44 a.m. Panel version: 0.1488 Biallelic pathogenic variants in RPIA cause Ribose 5-phosphate isomerase deficiency, MIM 608611. PMID: 14988808 is the first report on the disorder with molecular (incl. genetic) confirmation of the diagnosis. A patient initially investigated for early developmental delay, leukoencephalopathy, seizures with onset at 4 years, with subsequent neurologic regression and peripheral neuropathy at the age of 7, was suspected to have a disorder of the pentose phosphate pathway on the basis of highly elevated polyols on brain MRS and body fluid analysis. Reduced ribose 5-phosphate isomerase activity was shown in fibroblasts. Genetic testing demonstrated the presence of a missense (NM_144563.2:c.404C>T or p.Ala135Val - previously referred to as A61V) as well as a frameshift variant (NM_144563.2:c.762delG or p.Asn255Ilefs). Additional extensive supportive functional studies were published a few years later (PMID: 20499043). [This patient was initially described in PMID: 10589548]. PMID: 28801340 is a report on a second patient. This individual presented with delayed early development (independent walking and speech achieved at 2 and 5 years respectively), seizures and regression at the age of 7 with MRI white matter abnormalities. Review of magnetic resonance spectroscopy (MRS) was suggestive of elevated polyols (arabitol and ribitol). In line with this, genetic testing revealed a homozygous missense variant in RPIA (NM_144563.2:c.592T>C or p.Phe198Leu). Urine analysis confirmed elevated excretion of polyols, thus confirming the diagnosis. PMID: 30088433 reports on a boy with neonatal onset leukoencephalopathy and developmental delay having undergone early metabolic testing and aCGH (the latter at the age of 16 months). Persistance of his delay motivated exome sequencing at the age of approx. 4.5 years which demonstrated 2 RPIA variants (NM_144563.2:c.253G>A or p.Ala85Thr and NM_144563.2:c.347-1G>A). Measurement of ribitol and arabitol in urine demonstrated significant elevations (>20x) consistent with this diagnosis. 2 of the 3 patients described in the literature presented seizures. As a result this gene can be considered for inclusion in this panel as amber. [This gene is also present in the Undiagnosed metabolic disorders gene panel as red. Please consider upgrade based on these further publications.]. Sources: Literature |
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Undiagnosed metabolic disorders v1.81 | RPIA | Sarah Leigh Classified gene: RPIA as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.81 | RPIA | Sarah Leigh Added comment: Comment on list classification: Based on additional variants reported in PMIDs 28801340; 30088433. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.81 | RPIA | Sarah Leigh Gene: rpia has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.80 | RPIA | Sarah Leigh Classified gene: RPIA as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.80 | RPIA | Sarah Leigh Gene: rpia has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.79 | ATXN7_CAG | Louise Daugherty Classified STR: ATXN7_CAG as No list | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.79 | ATXN7_CAG | Louise Daugherty Added comment: Comment on list classification: Removed STR from Panel. This STR was not listed on the recent GMC STRs document supplied by Arianna Tucci. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders v1.78 | ISCA-37440-Loss |
Louise Daugherty Region: ISCA-37440-Loss was added Region: ISCA-37440-Loss was added to Undiagnosed metabolic disorders. Sources: ClinGen,Expert Review Green Mode of inheritance for Region: ISCA-37440-Loss was set to BIALLELIC, autosomal or pseudoautosomal Publications for Region: ISCA-37440-Loss were set to 11524703; 18234729; 16385448 Phenotypes for Region: ISCA-37440-Loss were set to mild/moderate mental retardation; facial dysmorphism; Hypotonia-cystinuria syndrome (HCS); 2p21 deletion syndrome; rapid weight gain in late childhood; failure to thrive; growth hormone deficiency; 606407; lactic acidemia; respiratory chain complex IV deficiency; hyperphagia; minor facial dysmorphism; severe somatic and developmental delay; nephrolithiasis; cystinuria; neonatal seizures; hypotonia |
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Undiagnosed metabolic disorders | GPD1 | Ellen McDonagh classified GPD1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | DNAJC19 | Ellen McDonagh classified DNAJC19 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | RPL10 | Sarah Leigh classified RPL10 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | KYNU | Ellen McDonagh classified KYNU as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | HAAO | Ellen McDonagh classified HAAO as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | HTRA2 | Sarah Leigh classified HTRA2 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | HAAO | Ellen McDonagh classified HAAO as amber | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | KYNU | Ellen McDonagh classified KYNU as amber | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | EPG5 | Ellen McDonagh classified EPG5 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | NGLY1 | Ellen McDonagh classified NGLY1 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | DNAJC12 | Rebecca Foulger classified DNAJC12 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | DNAJC12 | Rebecca Foulger classified DNAJC12 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | PIGT | Sarah Leigh classified PIGT as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | ATP7A | Sarah Leigh classified ATP7A as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | HPRT1 | Sarah Leigh classified HPRT1 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | WDR45 | Sarah Leigh classified WDR45 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | SLC39A14 | Sarah Leigh classified SLC39A14 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | PLA2G6 | Sarah Leigh classified PLA2G6 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | FA2H | Sarah Leigh classified FA2H as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | CP | Sarah Leigh classified CP as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | ATP7B | Sarah Leigh classified ATP7B as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | ATP13A2 | Sarah Leigh classified ATP13A2 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | ADAR | Sarah Leigh classified ADAR as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | HYAL1 | Sarah Leigh classified HYAL1 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | DBH | Sarah Leigh classified DBH as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | Sarah Leigh promoted panel to version 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | SLCO1B3 | Sarah Leigh classified SLCO1B3 as red | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | SLCO1B1 | Sarah Leigh classified SLCO1B1 as red | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | SI | Arianna Tucci reviewed SI | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | TALDO1 | Sarah Leigh classified TALDO1 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | DPM2 | Ellen McDonagh classified DPM2 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | ATIC | Richard Scott classified ATIC as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | SI | Sarah Leigh commented on SI | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | RBCK1 | Sarah Leigh classified RBCK1 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | SLC52A3 | Sarah Leigh classified SLC52A3 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | SLC52A2 | Sarah Leigh classified SLC52A2 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | HCFC1 | Sarah Leigh classified HCFC1 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | GLRA1 | Sarah Leigh classified GLRA1 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | GABRG2 | Sarah Leigh classified GABRG2 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | DBH | Sarah Leigh classified DBH as red | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | GCSH | Sarah Leigh classified GCSH as red | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | SLC36A2 | Sarah Leigh classified SLC36A2 as red | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | SLC6A19 | Sarah Leigh classified SLC6A19 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | QDPR | Sarah Leigh classified QDPR as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | PRKAG2 | Sarah Leigh classified PRKAG2 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | PHKA1 | Sarah Leigh classified PHKA1 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | PGK1 | Sarah Leigh classified PGK1 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | PAH | Sarah Leigh classified PAH as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | MAT1A | Sarah Leigh classified MAT1A as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | LAMP2 | Sarah Leigh classified LAMP2 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | L2HGDH | Sarah Leigh classified L2HGDH as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | HEXB | Sarah Leigh classified HEXB as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | HEXA | Sarah Leigh classified HEXA as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | GYG1 | Sarah Leigh classified GYG1 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | GLDC | Sarah Leigh classified GLDC as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | GCH1 | Sarah Leigh classified GCH1 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | GCDH | Sarah Leigh classified GCDH as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | GALK1 | Sarah Leigh classified GALK1 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | G6PC3 | Sarah Leigh classified G6PC3 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | G6PC3 | Sarah Leigh classified G6PC3 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | FUCA1 | Sarah Leigh classified FUCA1 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | DDC | Sarah Leigh classified DDC as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | D2HGDH | Sarah Leigh classified D2HGDH as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | CTSK | Sarah Leigh classified CTSK as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | CTSD | Sarah Leigh classified CTSD as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | CTSA | Sarah Leigh classified CTSA as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | CBS | Sarah Leigh classified CBS as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | ASPA | Sarah Leigh classified ASPA as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | AMT | Sarah Leigh classified AMT as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | AMN | Sarah Leigh classified AMN as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | ABCD4 | Sarah Leigh classified ABCD4 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | SUMF1 | Sarah Leigh classified SUMF1 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | SMPD1 | Sarah Leigh classified SMPD1 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | SLC17A5 | Sarah Leigh classified SLC17A5 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | PPT1 | Sarah Leigh classified PPT1 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | PFKM | Sarah Leigh classified PFKM as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | NPC2 | Sarah Leigh classified NPC2 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | NPC1 | Sarah Leigh classified NPC1 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | NAGA | Sarah Leigh classified NAGA as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | MTRR | Sarah Leigh classified MTRR as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | MTR | Sarah Leigh classified MTR as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | MMADHC | Sarah Leigh classified MMADHC as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | MMACHC | Sarah Leigh classified MMACHC as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | MFSD8 | Sarah Leigh classified MFSD8 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | MCCC2 | Sarah Leigh classified MCCC2 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | MCCC1 | Sarah Leigh classified MCCC1 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | MAN2B1 | Sarah Leigh classified MAN2B1 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | LPIN1 | Sarah Leigh classified LPIN1 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | LIPA | Sarah Leigh classified LIPA as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | HYAL1 | Sarah Leigh classified HYAL1 as red | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | GYS1 | Sarah Leigh classified GYS1 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | GM2A | Sarah Leigh classified GM2A as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | GM2A | Sarah Leigh classified GM2A as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | GALC | Sarah Leigh classified GALC as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | GAA | Sarah Leigh classified GAA as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | ENO3 | Sarah Leigh classified ENO3 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | CYP27A1 | Sarah Leigh classified CYP27A1 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | CLN8 | Sarah Leigh classified CLN8 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | CLN6 | Sarah Leigh classified CLN6 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | CLN5 | Sarah Leigh classified CLN5 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | CLN3 | Sarah Leigh classified CLN3 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | CD320 | Sarah Leigh classified CD320 as red | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | ARSA | Sarah Leigh classified ARSA as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | ALDH5A1 | Sarah Leigh classified ALDH5A1 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | AGA | Sarah Leigh classified AGA as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | RYR1 | Ellen McDonagh classified RYR1 as amber | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | BCKDK | Sarah Leigh classified BCKDK as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | BCKDK | Sarah Leigh classified BCKDK as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | BCKDK | Sarah Leigh classified BCKDK as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | CUBN | Sarah Leigh classified CUBN as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | ALDH4A1 | Sarah Leigh classified ALDH4A1 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | GALE | Sarah Leigh classified GALE as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | TPP1 | Sarah Leigh classified TPP1 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | DPYS | Sarah Leigh classified DPYS as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | AASS | Sarah Leigh classified AASS as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | GALT | Sarah Leigh classified GALT as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | UMPS | Sarah Leigh classified UMPS as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | SLC30A10 | Sarah Leigh classified SLC30A10 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | ALDH7A1 | Sarah Leigh classified ALDH7A1 as green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Undiagnosed metabolic disorders | ALDH7A1 | Sarah Leigh classified ALDH7A1 as green |