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Likely inborn error of metabolism - targeted testing not possible v4.137 ADA Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes: Combined B and T cell defect;Adenosine deaminase deficiency (Disorders of purine metabolism);SCID;Infantile enterocolitis & monogenic inflammatory bowel disease
Likely inborn error of metabolism - targeted testing not possible v4.137 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700 to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Likely inborn error of metabolism - targeted testing not possible v4.136 ADA Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes: Combined B and T cell defect;Adenosine deaminase deficiency (Disorders of purine metabolism);SCID;Infantile enterocolitis & monogenic inflammatory bowel disease
Likely inborn error of metabolism - targeted testing not possible v4.136 ADA Arina Puzriakova Phenotypes for gene: ADA were changed from Combined B and T cell defect; Adenosine deaminase deficiency (Disorders of purine metabolism); SCID; Infantile enterocolitis & monogenic inflammatory bowel disease to Severe combined immunodeficiency due to ADA deficiency, OMIM:102700; Adenosine deaminase deficiency, partial, OMIM:102700
Likely inborn error of metabolism - targeted testing not possible v4.132 ALAS2 Arina Puzriakova Phenotypes for gene: ALAS2 were changed from Erythropoietic protoporphyria, mild variant; X-linked sideroblastic anaemia (XLSA) (Porphyrias with acute painful photosensitivity); X-linked dominant protoporphyria (Porphyrias with acute painful photosensitivity) to Anemia, sideroblastic, 1, OMIM:300751; Protoporphyria, erythropoietic, X-linked, OMIM:300752
Likely inborn error of metabolism - targeted testing not possible v4.128 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
Likely inborn error of metabolism - targeted testing not possible v4.125 GSTZ1 Achchuthan Shanmugasundram Classified gene: GSTZ1 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v4.125 GSTZ1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reported in PMID:27876694 and reviewed by Saikat Santra, there are three boys and three girls with maleylacetoacetate isomerase deficiency (MAAID), identified by newborn screening with mildly elevated succinylacetone (SA) by mass spectrometry on dried blood spot.

Four of them were identified with homozygous GSTZ1 variants, one with compound heterozygous variants and one with heterozygous variant.

Hence, there is sufficient evidence available for the association of biallelic GSTZ1 variants with MAAID and this gene can be promoted to green rating in the next GMS review.
Likely inborn error of metabolism - targeted testing not possible v4.125 GSTZ1 Achchuthan Shanmugasundram Gene: gstz1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.122 GSTZ1 Saikat Santra gene: GSTZ1 was added
gene: GSTZ1 was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Literature,Expert Review,Eligibility statement prior genetic testing
Mode of inheritance for gene: GSTZ1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GSTZ1 were set to 27876694
Phenotypes for gene: GSTZ1 were set to Biochemical
Penetrance for gene: GSTZ1 were set to unknown
Review for gene: GSTZ1 was set to GREEN
Added comment: GSTZ1 is established as the molecular cause for maleylacetoacetate isomerase deficiency which is an established inherited metabolic disorder and associated with succinylacetone excretion so may be detected on newborn screening programmes for hereditary tyrosinaemia type1 (FAH). The committee established for developing the pathways for rolling this out recommended that genetic testing for GSTZ1 be made available via the R98 panel to help evaluate patients with mild hypersuccinylacetonaemia - but patients with elevated succinylacetone on routine metabolic testing would also benefit from this being available.
Sources: Literature, Expert Review, Eligibility statement prior genetic testing
Likely inborn error of metabolism - targeted testing not possible v4.122 COX5A Sarah Leigh edited their review of gene: COX5A: Added comment: To date, two COX5A variants have been associated with Mitochondrial complex IV deficiency, nuclear type 20 (OMIM:619064) in two unrelated cases (PMID: 28247525;35246835). Analysis of patient fibroblasts has revealed a reduced enzymatic activity and protein levels of complex IV and several of its subunits, plus, lentiviral complementation rescues the complex IV deficiency (PMID: 28247525;35246835).; Changed rating: GREEN
Likely inborn error of metabolism - targeted testing not possible v4.122 COX5A Sarah Leigh Classified gene: COX5A as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v4.122 COX5A Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism - targeted testing not possible v4.122 COX5A Sarah Leigh Gene: cox5a has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.118 VPS33A Sarah Leigh Classified gene: VPS33A as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v4.118 VPS33A Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism - targeted testing not possible v4.118 VPS33A Sarah Leigh Gene: vps33a has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.117 VPS33A Sarah Leigh gene: VPS33A was added
gene: VPS33A was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Other
Q4_23_promote_green tags were added to gene: VPS33A.
Mode of inheritance for gene: VPS33A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS33A were set to 28013294; 27547915; 31070736
Phenotypes for gene: VPS33A were set to Mucopolysaccharidosis-plus syndrome OMIM:617303; mucopolysaccharidosis-like syndrome with congenital heart defects and hematopoietic disorders MONDO:0015012
Review for gene: VPS33A was set to GREEN
Added comment: This gene has been copied from Lysosomal storage disorder panel:
Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least one variant was reported in two Turkish sisters (PMID 27547915) and in the Yakut population in the Russian Federation (PMID 28013294), where haplotype evidence suggested a founder effect in the Russian population. Supportive functional studies were also presented (PMID 31070736).
Sarah Leigh (Genomics England Curator), 17 Mar 2021
Single variant (R498W) reported in the Turkish and Yakut population. Functional studies support association of this gene to lysosomal dysfunction. Sources: Expert list
Zornitza Stark (Australian Genomics), 22 Jul 2020
Sources: Other
Likely inborn error of metabolism - targeted testing not possible v4.116 VPS16 Sarah Leigh Classified gene: VPS16 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v4.116 VPS16 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism - targeted testing not possible v4.116 VPS16 Sarah Leigh Gene: vps16 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.115 VPS16 Sarah Leigh Added comment: Comment on mode of inheritance: Biallelic variants are associated with a phenotype resembling a lysosomal storage disease. There are sufficient families (3) and functional data showing defects in the endolysosomal trafficking system to support inclusion for this allelic requirement. Monoallelic variants are linked to dystonia but only one study performed further analyses that suggested lysosomal dysfunction. Therefore while possible, it is unclear whether the 'Lysosomal storage disorder' panel would be applied in these cases. VPS16 will be flagged for GMS review with regards to the most appropriate MOI on this panel (biallelic or both bilalleic/monoallelic)
Arina Puzriakova (Genomics England Curator), 14 Jun 2021
Likely inborn error of metabolism - targeted testing not possible v4.114 VPS16 Sarah Leigh gene: VPS16 was added
gene: VPS16 was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Other
Q4_23_promote_green tags were added to gene: VPS16.
Mode of inheritance for gene: VPS16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS16 were set to 33938619; 34013567
Phenotypes for gene: VPS16 were set to Mucopolysaccharidosis-like syndrome (biallelic); Dystonia Associated with Lysosomal Abnormalities (monoallelic); Dystonia 30, OMIM:619291
Review for gene: VPS16 was set to GREEN
Added comment: Copied from Lysosomal storage disorder panel: Four individuals from three families were identified (PMIDs: 33938619; 34013567) exhibiting a mucopolysaccharidosis (MPS)-like lysosomal storage phenotype with short stature, coarse facies, DD or regression, peripheral neuropathy, skeletal dysplasia, neutropenia, and high-normal glycosaminoglycan excretion. All harboured homozygous variants in VPS16 which segregated with disease, including a missense variant in a sib pair (c.540G>T; p.Trp180Cys) and a recurrent intronic variant (c.2272‐18C>A) in two supposedly unrelated patients (although both of Middle Eastern descent). Fibroblasts of the two patients with the intronic variant showed accumulation of lysosomal compartments and autophagosomes with significantly decreased VPS16 mRNA and protein levels, as well as HOPS/CORVET complexes. Cellular phenotypes were rescued upon re-expression of wild-type VPS16. ----- Heterozygous variants, as well as a homozygous missense variant (c.156C>A) found in a consanguineous Chinese family (PMID:27174565), have been found to cause dystonia with variable onset (OMIM:619291). It has been suggested that the discrepancies in patient phenotypes are due to different mechanisms of pathogenicity, where variants causing dystonia do not affect the levels of endolysosomal tethering (HOPS/CORVET) complexes. More research is needed to clarify the mechanisms underlying VPS16-related dystonia as only limited functional data is currently available - Steel et al. 2020 (PMID:32808683) did perform electron microscopic studies of lymphocytes and fibroblasts derived from 2 unrelated patients, which showed vacuolar abnormalities suggestive of impaired lysosomal function. Sources: Literature
Arina Puzriakova (Genomics England Curator), 14 Jun 2021
Sources: Other
Likely inborn error of metabolism - targeted testing not possible v4.113 CLCN7 Sarah Leigh gene: CLCN7 was added
gene: CLCN7 was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Expert Review Amber,Literature
watchlist tags were added to gene: CLCN7.
Mode of inheritance for gene: CLCN7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CLCN7 were set to 31155284
Phenotypes for gene: CLCN7 were set to Hypopigmentation, organomegaly, and delayed myelination and development, OMIM:618541
Mode of pathogenicity for gene: CLCN7 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Likely inborn error of metabolism - targeted testing not possible v4.112 KCTD7 Sarah Leigh gene: KCTD7 was added
gene: KCTD7 was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Other
Mode of inheritance for gene: KCTD7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: KCTD7 were set to Epilepsy, progressive myoclonic 3, with or without intracellular inclusions OMIM:611726; progressive myoclonic epilepsy type 3 MONDO:0012721
Review for gene: KCTD7 was set to RED
Added comment: Although this gene is rated as Green on the Neuronal ceroid lipofuscinosis panel, it is not considered to be a metabolic gene and so is rated Red on this panel.
Sources: Other
Likely inborn error of metabolism - targeted testing not possible v4.111 GRN Sarah Leigh Entity copied from Neuronal ceroid lipofuscinosis v2.6
Likely inborn error of metabolism - targeted testing not possible v4.111 GRN Sarah Leigh gene: GRN was added
gene: GRN was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Expert Review Amber,NHS GMS,London North GLH
Q4_22_promote_green tags were added to gene: GRN.
Mode of inheritance for gene: GRN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRN were set to 22608501; 27021778; 28000352; 28404863; 30922528; 31855245
Phenotypes for gene: GRN were set to Ceroid lipofuscinosis, neuronal, 11 OMIM:614706; neuronal ceroid lipofuscinosis 11 MONDO:0013866
Likely inborn error of metabolism - targeted testing not possible v4.110 CTSF Sarah Leigh Classified gene: CTSF as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v4.110 CTSF Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism - targeted testing not possible v4.110 CTSF Sarah Leigh Gene: ctsf has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.109 CTSF Sarah Leigh gene: CTSF was added
gene: CTSF was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Expert list
Q4_23_promote_green tags were added to gene: CTSF.
Mode of inheritance for gene: CTSF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTSF were set to 23297359; 25274848
Phenotypes for gene: CTSF were set to Ceroid lipofuscinosis, neuronal, 13, Kufs type OMIM:615362; neuronal ceroid lipofuscinosis 13 MONDO:0014147
Likely inborn error of metabolism - targeted testing not possible v4.108 CLCN6 Sarah Leigh commented on gene: CLCN6: Although this gene is rated as Green on the Neuronal ceroid lipofuscinosis panel, it is not considered to be a metabolic gene and so is rated Red on this panel.
Likely inborn error of metabolism - targeted testing not possible v4.108 CLCN6 Sarah Leigh gene: CLCN6 was added
gene: CLCN6 was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Other
Mode of inheritance for gene: CLCN6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CLCN6 were set to 29667327; 26658788; 25794116; 21107136; 33217309; 16950870
Phenotypes for gene: CLCN6 were set to Neurodegeneration, childhood-onset, hypotonia, respiratory insufficiency and brain imaging abnormalities OMIM:619173
Review for gene: CLCN6 was set to RED
Added comment: Sources: Other
Likely inborn error of metabolism - targeted testing not possible v4.107 LMF1 Sarah Leigh Classified gene: LMF1 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v4.107 LMF1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism - targeted testing not possible v4.107 LMF1 Sarah Leigh Gene: lmf1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.106 LMF1 Sarah Leigh changed review comment from: PMID 17994020 and 19820022, both report homozygous terminating variants in severe hypertriglyceridemia, together with functional studies that showed significant reduction of LPL activity. PMID 30885219: heterozygous LMF1 c.1024C > T (p.Arg342*; rs776584760) in a patient with Hypertriglyceridemia and acute pancreatitis (HTG-AP). PMID: 30420299 reports at least 2 likely pathogenic (terminating variants) heterozygous LMF1 variants from 13 variants in severe hypertriglyceridemia patients. PMID: 29910226 reports a compound heterozygous variants (c.257C>T, p.P86L & c.1184C>T,p.T395I) which segrates with hypertriglyceridemia in the family. However PMID: 22239554 reports that a number of missense variants don't have an effect.; to: PMID 17994020 and 19820022, both report homozygous terminating variants in severe hypertriglyceridemia, together with functional studies that showed significant reduction of LPL activity. PMID 30885219: heterozygous LMF1 c.1024C > T (p.Arg342*; rs776584760) in a patient with Hypertriglyceridemia and acute pancreatitis (HTG-AP). PMID: 30420299 reports at least 2 likely pathogenic (terminating variants) heterozygous LMF1 variants from 13 variants in severe hypertriglyceridemia patients. PMID: 29910226 reports a compound heterozygous variants (c.257C>T, p.P86L & c.1184C>T,p.T395I) which segregates with hypertriglyceridemia in the family. However PMID: 22239554 reports that a number of missense variants don't have an effect.
Likely inborn error of metabolism - targeted testing not possible v4.106 LMF1 Sarah Leigh commented on gene: LMF1: PMID 17994020 and 19820022, both report homozygous terminating variants in severe hypertriglyceridemia, together with functional studies that showed significant reduction of LPL activity. PMID 30885219: heterozygous LMF1 c.1024C > T (p.Arg342*; rs776584760) in a patient with Hypertriglyceridemia and acute pancreatitis (HTG-AP). PMID: 30420299 reports at least 2 likely pathogenic (terminating variants) heterozygous LMF1 variants from 13 variants in severe hypertriglyceridemia patients. PMID: 29910226 reports a compound heterozygous variants (c.257C>T, p.P86L & c.1184C>T,p.T395I) which segrates with hypertriglyceridemia in the family. However PMID: 22239554 reports that a number of missense variants don't have an effect.
Likely inborn error of metabolism - targeted testing not possible v4.106 LMF1 Sarah Leigh gene: LMF1 was added
gene: LMF1 was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Expert list
Q4_23_promote_green tags were added to gene: LMF1.
Mode of inheritance for gene: LMF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LMF1 were set to 17994020; 19820022; 30885219; 30420299; 29910226; 22239554
Phenotypes for gene: LMF1 were set to Lipase deficiency, combined OMIM:246650; lipase deficiency, combined MONDO:0009527
Review for gene: LMF1 was set to GREEN
gene: LMF1 was marked as current diagnostic
Added comment: LMF1 Familial chylomicronaemia syndrome (FCS) panel.
Maggie Williams (North Bristol NHS Trust) [email protected]: Variants in this GENE are reported as part of current diagnostic practice
Sources: Expert list
Likely inborn error of metabolism - targeted testing not possible v4.105 GPIHBP1 Sarah Leigh Classified gene: GPIHBP1 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v4.105 GPIHBP1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism - targeted testing not possible v4.105 GPIHBP1 Sarah Leigh Gene: gpihbp1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.104 GPIHBP1 Sarah Leigh gene: GPIHBP1 was added
gene: GPIHBP1 was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Expert list
Q4_23_promote_green tags were added to gene: GPIHBP1.
Mode of inheritance for gene: GPIHBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GPIHBP1 were set to Hyperlipoproteinemia, type 1D OMIM:615947; hyperlipoproteinemia, type 1D MONDO:0014412
Review for gene: GPIHBP1 was set to GREEN
Added comment: GPIHBP1 copied from Familial chylomicronaemia syndrome (FCS) panel.
Maggie Williams (North Bristol NHS Trust)([email protected]): Variants in this GENE are reported as part of current diagnostic practice
Sources: Expert list
Likely inborn error of metabolism - targeted testing not possible v4.103 OSTC Sarah Leigh gene: OSTC was added
gene: OSTC was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Literature,Expert Review Red
Mode of inheritance for gene: OSTC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OSTC were set to 32267060
Phenotypes for gene: OSTC were set to Oligosaccharyltransferase complex-congenital disorders of glycosylation
Likely inborn error of metabolism - targeted testing not possible v4.102 EDEM3 Sarah Leigh Classified gene: EDEM3 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v4.102 EDEM3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism - targeted testing not possible v4.102 EDEM3 Sarah Leigh Gene: edem3 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.101 EDEM3 Sarah Leigh gene: EDEM3 was added
gene: EDEM3 was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Other
Q4_23_promote_green tags were added to gene: EDEM3.
Mode of inheritance for gene: EDEM3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EDEM3 were set to 34143952
Phenotypes for gene: EDEM3 were set to Congenital disorder of glycosylation, type 2V, OMIM:619493
Review for gene: EDEM3 was set to GREEN
Added comment: Reviews copied from entry on Congenital disorders of glycosylation panel.
There is sufficient evidence to promote this gene to Green at the next GMS panel update. EDEM3 is associated with a relevant phenotype in OMIM (MIM# 619493) and G2P with a 'strong' confidence level assertion. 12 individuals from 7 unrelated families identified by Polla et al. 2021 (PMID: 34143952) with various biallelic variants in the EDEM3 gene. Clinical characteristics were predominant for DD (12/12), ID (6/7), hypotonia (6/12) and facial dysmorphisms. (Arina Puzriakova (Genomics England Curator), 18 Jul 2022).
PMID: 34143952: 7 families (11 individuals) with 6x PTV and 2x missense variants with neurodevelopmental delay and variable facial dysmorphisms. The unaffected parents were all heterozygous carriers. Functional studies show loss of EDEM3 enzymatic activity. Sources: Literature (Zornitza Stark (Australian Genomics), 7 Aug 2021).
Sources: Other
Likely inborn error of metabolism - targeted testing not possible v4.100 CAMLG Sarah Leigh gene: CAMLG was added
gene: CAMLG was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Literature
Mode of inheritance for gene: CAMLG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAMLG were set to 35262690
Phenotypes for gene: CAMLG were set to Congenital disorder of glycosylation, type IIz, OMIM:620201
Likely inborn error of metabolism - targeted testing not possible v4.99 ALG10 Sarah Leigh gene: ALG10 was added
gene: ALG10 was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Literature,Expert Review Red
Mode of inheritance for gene: ALG10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALG10 were set to 33798445
Phenotypes for gene: ALG10 were set to Progressive myoclonus epilepsy; CDG
Likely inborn error of metabolism - targeted testing not possible v4.98 MAN2B2 Sarah Leigh gene: MAN2B2 was added
gene: MAN2B2 was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Literature,Expert Review Amber
Mode of inheritance for gene: MAN2B2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAN2B2 were set to 31775018; 35637269
Phenotypes for gene: MAN2B2 were set to congenital disorder of glycosylation, MONDO:0015286
Likely inborn error of metabolism - targeted testing not possible v4.97 COG3 Sarah Leigh gene: COG3 was added
gene: COG3 was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Literature,Expert Review Amber
Mode of inheritance for gene: COG3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COG3 were set to 37711075
Phenotypes for gene: COG3 were set to Congenital disorder of glycosylation, type IIbb, OMIM:620546
Likely inborn error of metabolism - targeted testing not possible v4.96 TRIT1 Eleanor Williams Phenotypes for gene: TRIT1 were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 35, OMIM :617873 to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 35, OMIM :617873; combined oxidative phosphorylation deficiency 35, MONDO:0054742
Likely inborn error of metabolism - targeted testing not possible v4.95 NUS1 Achchuthan Shanmugasundram Classified gene: NUS1 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v4.95 NUS1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As there is sufficient evidence available for the association of monoallelic NUS1 variants with intellectual disability and epilepsy, this gene can be promoted to green rating in the next GMS review.
Likely inborn error of metabolism - targeted testing not possible v4.95 NUS1 Achchuthan Shanmugasundram Gene: nus1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.87 LDHD Sarah Leigh Classified gene: LDHD as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v4.87 LDHD Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism - targeted testing not possible v4.87 LDHD Sarah Leigh Gene: ldhd has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.84 LDHD Sarah Leigh Classified gene: LDHD as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v4.84 LDHD Sarah Leigh Gene: ldhd has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.84 LDHD Sarah Leigh Classified gene: LDHD as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v4.84 LDHD Sarah Leigh Gene: ldhd has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.78 ACACA Sarah Leigh Classified gene: ACACA as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v4.78 ACACA Sarah Leigh Gene: acaca has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.77 LDHD Hannah Knight gene: LDHD was added
gene: LDHD was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Literature
Mode of inheritance for gene: LDHD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LDHD were set to 30931947; 31638601
Phenotypes for gene: LDHD were set to D-lactic aciduria with susceptibility to gout
Review for gene: LDHD was set to AMBER
Added comment: PMID: 30931947 (2019) reported two unrelated patients with homozygous missense variants in LDHD (p.Thr463Met and p.Trp374Cys)
PMID: 31638601 (2019) reported a 4-generation consanguineous Bedouin-Israeli family with autosomal recessive hyperuricemia. A homozygous missense variant in LDHD was identified (p.R370W)
Sources: Literature
Likely inborn error of metabolism - targeted testing not possible v4.77 ACACA Hannah Knight gene: ACACA was added
gene: ACACA was added to Likely inborn error of metabolism - targeted testing not possible. Sources: Literature
Mode of inheritance for gene: ACACA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACACA were set to 34552920
Phenotypes for gene: ACACA were set to Acetyl-CoA carboxylase deficiency
Review for gene: ACACA was set to AMBER
Added comment: PMID: 34552920 (2021) reported a baby who presented in her first two years of life with global developmental delay, microcephaly, hypotonia, and dysmorphic facial features. Two VUS's in ACACA were identified, and a decreased level of ACC1 and ACC1 enzyme activity was detected in patient-derived lymphocytes. In vitro studies revealed a disruption of lipid homeostasis in patient-derived lymphocytes, further inducing the deficit of cell motility capacity and that the deficiency could be partly attenuated by palmitate.
Sources: Literature
Likely inborn error of metabolism - targeted testing not possible v4.77 PIGM Sarah Leigh edited their review of gene: PIGM: Added comment: 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).; Changed rating: GREEN
Likely inborn error of metabolism - targeted testing not possible v4.77 PIGM Sarah Leigh Classified gene: PIGM as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v4.77 PIGM Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism - targeted testing not possible v4.77 PIGM Sarah Leigh Gene: pigm has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.76 PIGM Sarah Leigh Phenotypes for gene: PIGM were changed from Glycosylphosphatidylinositol deficiency 610293 to Glycosylphosphatidylinositol deficiency, OMIM:610293
Likely inborn error of metabolism - targeted testing not possible v4.74 PIGM Hannah Knight reviewed gene: PIGM: Rating: GREEN; Mode of pathogenicity: None; Publications: 31445883; Phenotypes: Glycosylphosphatidylinositol deficiency 610293; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism - targeted testing not possible v4.74 HSPA9 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.; to: Comment on list classification: As reviewed by Hannah Knight, there is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Likely inborn error of metabolism - targeted testing not possible v4.74 HSPA9 Achchuthan Shanmugasundram Classified gene: HSPA9 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v4.74 HSPA9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Likely inborn error of metabolism - targeted testing not possible v4.74 HSPA9 Achchuthan Shanmugasundram Gene: hspa9 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.69 ATP5B Sarah Leigh Classified gene: ATP5B as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v4.69 ATP5B Sarah Leigh Gene: atp5b has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.64 PTCD3 Sarah Leigh edited their review of gene: PTCD3: Added comment: PTCD3 variants are associated with ?Combined oxidative phosphorylation deficiency 51 (OMIM:619057), but not associated with phenotype in Gen2Phen. At least six variants have been reported in three unrelated cases, with OMIM:619057 (PMID: 30607703; 36450274). Functional studies also support the involvement of PTCD3 variants in this condition (PMID: 30607703; 36450274).; Changed rating: GREEN
Likely inborn error of metabolism - targeted testing not possible v4.63 PTCD3 Sarah Leigh Classified gene: PTCD3 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v4.63 PTCD3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism - targeted testing not possible v4.63 PTCD3 Sarah Leigh Gene: ptcd3 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.59 MRM2 Sarah Leigh Classified gene: MRM2 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v4.59 MRM2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism - targeted testing not possible v4.59 MRM2 Sarah Leigh Gene: mrm2 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.57 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, the MOI should be updated from 'Both mono- and biallelic' to 'Biallelic' only at the next GMS panel update.
Likely inborn error of metabolism - targeted testing not possible v4.52 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
Likely inborn error of metabolism - targeted testing not possible v4.52 GCSH Arina Puzriakova Phenotypes for gene: GCSH were changed from ?Glycine encephalopathy, OMIM:605899; Neurodevelopmental disorder, MONDO:0700092 to Multiple mitochondrial dysfunctions syndrome 7, OMIM:620423; Glycine encephalopathy; Transient neonatal hyperglycinemia
Likely inborn error of metabolism - targeted testing not possible v4.47 COQ4 Achchuthan Shanmugasundram Phenotypes for gene: COQ4 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, 7 to Coenzyme Q10 deficiency, primary, 7, OMIM:616276
Likely inborn error of metabolism - targeted testing not possible v4.46 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
Likely inborn error of metabolism - targeted testing not possible v4.44 LETM1 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM and as moderate Gen2Phen gene. PMID: 36055214 reports 12 LETM1 variants in 11 unrelated cases of Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction (OMIM: 620089), together with supportive functional studies.; to: LETM1 variants have been associated with Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction, OMIM:620089 and as moderate Gen2Phen gene for LETM1-related neurodevelopmental disorder.
PMID: 36055214 reports 10 LETM1 variants in 18 patients from 11 unrelated families with childhood-onset neurodegeneration with multisystem involvement, many of whom were gathered using the GeneMatcher Program. The most common clinical features of this cohort, where an assessment could be made, were: mitochondrial respiratory complex deficiencies 11/11 (100%), global developmental delay / intellectual disability 17/18 (94%), bilateral sensorineural hearing loss 11/14 (78%) , impaired vision 10/10 (100%), cerebellar ataxia 7/9 (78%), seizures 10/15 (67%), hypotonia 11/18 (61%) (PMID: 36055214, figure 1c).
Likely inborn error of metabolism - targeted testing not possible v4.35 LETM1 Sarah Leigh Classified gene: LETM1 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v4.35 LETM1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism - targeted testing not possible v4.35 LETM1 Sarah Leigh Gene: letm1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.33 LETM1 Sarah Leigh Phenotypes for gene: LETM1 were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis) to Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction, OMIM:620089
Likely inborn error of metabolism - targeted testing not possible v4.31 OGDH Sarah Leigh Classified gene: OGDH as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v4.31 OGDH Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism - targeted testing not possible v4.31 OGDH Sarah Leigh Gene: ogdh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.27 PNPLA2 Achchuthan Shanmugasundram Classified gene: PNPLA2 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v4.27 PNPLA2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next GMS update.
Likely inborn error of metabolism - targeted testing not possible v4.27 PNPLA2 Achchuthan Shanmugasundram Gene: pnpla2 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.27 PNPLA2 Achchuthan Shanmugasundram Classified gene: PNPLA2 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v4.27 PNPLA2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next GMS update.
Likely inborn error of metabolism - targeted testing not possible v4.27 PNPLA2 Achchuthan Shanmugasundram Gene: pnpla2 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.27 PNPLA2 Achchuthan Shanmugasundram Classified gene: PNPLA2 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v4.27 PNPLA2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next GMS update.
Likely inborn error of metabolism - targeted testing not possible v4.27 PNPLA2 Achchuthan Shanmugasundram Gene: pnpla2 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.27 PNPLA2 Achchuthan Shanmugasundram Classified gene: PNPLA2 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v4.27 PNPLA2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next GMS update.
Likely inborn error of metabolism - targeted testing not possible v4.27 PNPLA2 Achchuthan Shanmugasundram Gene: pnpla2 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.27 PNPLA2 Achchuthan Shanmugasundram Classified gene: PNPLA2 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v4.27 PNPLA2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next GMS update.
Likely inborn error of metabolism - targeted testing not possible v4.27 PNPLA2 Achchuthan Shanmugasundram Gene: pnpla2 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.23 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
Likely inborn error of metabolism - targeted testing not possible v4.18 NDUFB7 Arina Puzriakova Phenotypes for gene: NDUFB7 were changed from Congenital lactic acidosis; hypertrophic cardiomyopathy to ?Mitochondrial complex I deficiency, nuclear type 39, OMIM:620135
Likely inborn error of metabolism - targeted testing not possible v4.12 GFM2 Arina Puzriakova Phenotypes for gene: GFM2 were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Early-onset neurological presentations of mitochondrial disease to Combined oxidative phosphorylation deficiency 39, OMIM:618397
Likely inborn error of metabolism - targeted testing not possible v4.10 GATB Arina Puzriakova Phenotypes for gene: GATB were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis) to ?Combined oxidative phosphorylation deficiency 41, OMIM:618838
Likely inborn error of metabolism - targeted testing not possible v4.4 ATP5O Arina Puzriakova Classified gene: ATP5O as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v4.4 ATP5O Arina Puzriakova Added comment: Comment on list classification: There are now sufficient unrelated cases reported (3) to promote this gene to Green at the next GMS panel update.
Likely inborn error of metabolism - targeted testing not possible v4.4 ATP5O Arina Puzriakova Gene: atp5o has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v4.2 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 mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Likely inborn error of metabolism - targeted testing not possible v4.2 SPG7 Sarah Leigh Added comment: Comment on phenotypes: Miscellaneous disorders/unknown function (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Spastic paraplegia 7, autosomal recessive, 607259;Disorders of mitochondrial DNA maintenance and integrity
Likely inborn error of metabolism - targeted testing not possible v4.2 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Miscellaneous disorders/unknown function (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Spastic paraplegia 7, autosomal recessive, 607259; Disorders of mitochondrial DNA maintenance and integrity to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Likely inborn error of metabolism - targeted testing not possible v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2023-03-22
Likely inborn error of metabolism - targeted testing not possible v4.0 Arina Puzriakova promoted panel to version 4.0
Likely inborn error of metabolism - targeted testing not possible v3.21 Catherine Snow Panel name changed from Inborn errors of metabolism to Likely inborn error of metabolism - targeted testing not possible
List of related panels changed from Likely inborn error of metabolism - targeted testing not possible; Likely inborn error of metabolism; R98 to Likely inborn error of metabolism - targeted testing not possible; Likely inborn error of metabolism; Inborn errors of metabolism; R98
Likely inborn error of metabolism - targeted testing not possible v3.20 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.20 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism - targeted testing not possible v3.20 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.19 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.19 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism - targeted testing not possible v3.19 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.20 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.20 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism - targeted testing not possible v3.20 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.20 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.20 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism - targeted testing not possible v3.20 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.20 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.20 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism - targeted testing not possible v3.20 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.20 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.20 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism - targeted testing not possible v3.20 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.19 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.19 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism - targeted testing not possible v3.19 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.19 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.19 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism - targeted testing not possible v3.19 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.19 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.19 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism - targeted testing not possible v3.19 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.18 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.18 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism - targeted testing not possible v3.18 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.18 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.18 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism - targeted testing not possible v3.18 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.18 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.18 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism - targeted testing not possible v3.18 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.17 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.17 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism - targeted testing not possible v3.17 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.18 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.18 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism - targeted testing not possible v3.18 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.17 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.17 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism - targeted testing not possible v3.17 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.17 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.17 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism - targeted testing not possible v3.17 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.17 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.17 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism - targeted testing not possible v3.17 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.17 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.17 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to green at the next NHS GMS review.
Likely inborn error of metabolism - targeted testing not possible v3.17 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.17 GCSH Achchuthan Shanmugasundram Classified gene: GCSH as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.17 GCSH Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence for this gene to be promoted to GREEN at the next NHS GMS review.
Likely inborn error of metabolism - targeted testing not possible v3.17 GCSH Achchuthan Shanmugasundram Gene: gcsh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.13 SLC31A1 Achchuthan Shanmugasundram Classified gene: SLC31A1 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.13 SLC31A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases reported with neurodegeneration associated with copper deficiency.

This gene has been associated with phenotype in Gene2Phenotype, but not in OMIM.
Likely inborn error of metabolism - targeted testing not possible v3.13 SLC31A1 Achchuthan Shanmugasundram Gene: slc31a1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.13 SLC31A1 Achchuthan Shanmugasundram Classified gene: SLC31A1 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.13 SLC31A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases reported with neurodegeneration associated with copper deficiency.

This gene has been associated with phenotype in Gene2Phenotype, but not in OMIM.
Likely inborn error of metabolism - targeted testing not possible v3.13 SLC31A1 Achchuthan Shanmugasundram Gene: slc31a1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.13 SLC31A1 Achchuthan Shanmugasundram Classified gene: SLC31A1 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.13 SLC31A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases reported with neurodegeneration associated with copper deficiency.

This gene has been associated with phenotype in Gene2Phenotype, but not in OMIM.
Likely inborn error of metabolism - targeted testing not possible v3.13 SLC31A1 Achchuthan Shanmugasundram Gene: slc31a1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.12 SLC31A1 Achchuthan Shanmugasundram Classified gene: SLC31A1 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.12 SLC31A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases reported with neurodegeneration associated with copper deficiency.

This gene has been associated with phenotype in Gene2Phenotype, but not in OMIM.
Likely inborn error of metabolism - targeted testing not possible v3.12 SLC31A1 Achchuthan Shanmugasundram Gene: slc31a1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.12 SLC31A1 Achchuthan Shanmugasundram Classified gene: SLC31A1 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.12 SLC31A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases reported with neurodegeneration associated with copper deficiency.

This gene has been associated with phenotype in Gene2Phenotype, but not in OMIM.
Likely inborn error of metabolism - targeted testing not possible v3.12 SLC31A1 Achchuthan Shanmugasundram Gene: slc31a1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.12 SLC31A1 Achchuthan Shanmugasundram Classified gene: SLC31A1 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.12 SLC31A1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated AMBER as there are two unrelated cases reported with neurodegeneration associated with copper deficiency.

This gene has been associated with phenotype in Gene2Phenotype, but not in OMIM.
Likely inborn error of metabolism - targeted testing not possible v3.12 SLC31A1 Achchuthan Shanmugasundram Gene: slc31a1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.11 SLC31A1 Achchuthan Shanmugasundram gene: SLC31A1 was added
gene: SLC31A1 was added to Inborn errors of metabolism. Sources: Literature
Mode of inheritance for gene: SLC31A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC31A1 were set to 35913762; 36562171
Phenotypes for gene: SLC31A1 were set to Neurodevelopmental disorder, MONDO:0700092
Review for gene: SLC31A1 was set to AMBER
Added comment: PMID:35913762 reported an identical twin male infants identified with homozygous novel missense variant p.Arg95His in CTR1. The twins had hypotonia, global developmental delay, seizures, and rapid brain atrophy, consistent with profound central nervous system copper deficiency. In addition, the CSF copper levels were lower and functional studies including structural modelling of the variant showed impaired copper transport. Treatment with copper Histidinate in the patients' cultured cells and in the patients normalized CCO activity and enhanced mitochondrial respiration in vitro, and was associated with modest clinical improvements.

PMID:36562171 reported a newborn infant of consanguineous parents with a homozygous pathogenic variant p.Leu79Pro in CTR1. This infant was born with pulmonary hypoplasia. At two weeks of age, multifocal brain hemorrhages were diagnosed and the infant developed seizures. Laboratory investigations revealed very low serum concentrations of copper and ceruloplasmin. The infant died at one month of age.
Sources: Literature
Likely inborn error of metabolism - targeted testing not possible v3.10 CRLS1 Achchuthan Shanmugasundram Classified gene: CRLS1 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.10 CRLS1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are three unrelated cases and supporting functional evidence to link this gene with a mitochondrial metabolic disorder. This gene has already been associated with this phenotype in OMIM (MIM #620167).
Likely inborn error of metabolism - targeted testing not possible v3.10 CRLS1 Achchuthan Shanmugasundram Gene: crls1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.10 CRLS1 Achchuthan Shanmugasundram Classified gene: CRLS1 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.10 CRLS1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are three unrelated cases and supporting functional evidence to link this gene with a mitochondrial metabolic disorder. This gene has already been associated with this phenotype in OMIM (MIM #620167).
Likely inborn error of metabolism - targeted testing not possible v3.10 CRLS1 Achchuthan Shanmugasundram Gene: crls1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.9 CRLS1 Achchuthan Shanmugasundram Classified gene: CRLS1 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.9 CRLS1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are three unrelated cases and supporting functional evidence to link this gene with a mitochondrial metabolic disorder. This gene has already been associated with this phenotype in OMIM (MIM #620167).
Likely inborn error of metabolism - targeted testing not possible v3.9 CRLS1 Achchuthan Shanmugasundram Gene: crls1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.9 CRLS1 Achchuthan Shanmugasundram Classified gene: CRLS1 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v3.9 CRLS1 Achchuthan Shanmugasundram Added comment: Comment on list classification: This gene should be rated GREEN as there are three unrelated cases and supporting functional evidence to link this gene with a mitochondrial metabolic disorder. This gene has already been associated with this phenotype in OMIM (MIM #620167).
Likely inborn error of metabolism - targeted testing not possible v3.9 CRLS1 Achchuthan Shanmugasundram Gene: crls1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v3.8 CRLS1 Achchuthan Shanmugasundram gene: CRLS1 was added
gene: CRLS1 was added to Inborn errors of metabolism. Sources: Literature
Mode of inheritance for gene: CRLS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CRLS1 were set to 35147173
Phenotypes for gene: CRLS1 were set to Combined oxidative phosphorylation deficiency 57, OMIM:620167
Review for gene: CRLS1 was set to GREEN
Added comment: Three individuals from two unrelated families were identified with the same homozygous variant in CRLS1 (p.Ile109Asn). They presented with a mitochondrial disorder characterized by an evolving pattern of cardiomyopathy, encephalopathy, bilateral auditory neuropathy spectrum disorder, bull’s eye maculopathy, diabetes insipidus, autonomic instability and low complex IV activity in skeletal muscle.

A fourth individual was identified with a compound heterozygous CRLS1 variant (p.Ala172Asp/ p.Leu217Phe) that presented with developmental regression beginning in late infancy, with acquired microcephaly, sensorineural hearing loss and impaired vision.

Lipidomics in fibroblasts from 2 patients demonstrated that cardiolipin was reduced, cardiolipin acyl side chains had an abnormal distribution, and substrates of CRLS1 were abnormally elevated, including an elevation of phosphatidylglycerol.
Sources: Literature
Likely inborn error of metabolism - targeted testing not possible v3.3 COX10 Arina Puzriakova Phenotypes for gene: COX10 were changed from Encephalopathy, progressive mitochondrial, with proximal renal tubulopathy due to cytochrome coxidase deficiency; Mitochondrial Diseases; Mitochondrial Respiratory Chain Complex IV Deficiency; Isolated complex IV deficiency; Complex IV (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors) to Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046; Encephalopathy, progressive mitochondrial, with proximal renal tubulopathy due to cytochrome coxidase deficiency
Likely inborn error of metabolism - targeted testing not possible v3.2 SLC26A6 Arina Puzriakova gene: SLC26A6 was added
gene: SLC26A6 was added to Inborn errors of metabolism. Sources: Literature
watchlist tags were added to gene: SLC26A6.
Mode of inheritance for gene: SLC26A6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SLC26A6 were set to 35115415
Phenotypes for gene: SLC26A6 were set to Enteric hyperoxaluria and nephrolithiasis
Added comment: Cornière et al. 2022 (PMID: 35115415) identified a single family with a heterozygous missense VUS (c.1519C>T/p.R507W) in the SLC26A6 gene. However, the variant was found in 5 out of 280 674 alleles reported in gnomAD (Europeans and South Asians). In vitro studies showed that the variant affects both SLC26A6 transport activity and membrane surface expression, in turn reducing Cl− dependant oxalate transport. Cotransfection studies indicated a dominant-negative effect on WT. Slc26a6 null mice similarly displayed hyperoxalemia and hyperoxaluria which were caused by defective intestinal back-secretion of dietary oxalate (PMID: 21170874; 32660969)

SLC26A6 is currently not associated with any human phenotype in OMIM or G2P.
Sources: Literature
Likely inborn error of metabolism - targeted testing not possible v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2022-11-30
Likely inborn error of metabolism - targeted testing not possible v3.0 Eleanor Williams promoted panel to version 3.0
Likely inborn error of metabolism - targeted testing not possible v2.329 ARSK Arina Puzriakova Classified gene: ARSK as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.329 ARSK Arina Puzriakova Added comment: Comment on list classification: Rating Amber awaiting further cases.
Likely inborn error of metabolism - targeted testing not possible v2.329 ARSK Arina Puzriakova Gene: arsk has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.328 ARSK Arina Puzriakova gene: ARSK was added
gene: ARSK was added to Inborn errors of metabolism. Sources: Literature
Mode of inheritance for gene: ARSK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARSK were set to 34916232
Phenotypes for gene: ARSK were set to Mucopolysaccharidoses with short stature, coarse facial features and dysostosis multiplex
Review for gene: ARSK was set to AMBER
Added comment: Verheyen et al. 2022 (PMID: 34916232) reported four affected individuals of two unrelated consanguineous families with homozygous variants c.250C>T, p.(Arg84Cys) and c.560T>A, p.(Leu187Ter) in ARSK, respectively. Patients were affected with skeletal dysplasia, resembling spondyloepiphysial dysplasia. Reverse phenotyping in two individuals from one family revealed additional cardiac and ophthalmological abnormalities.
Sources: Literature
Likely inborn error of metabolism - targeted testing not possible v2.327 HFE Arina Puzriakova Phenotypes for gene: HFE were changed from Hemochromatosis, 235200; Hereditary haemochromatosis Type 1 (Disorder of iron metabolism) to Hemochromatosis, OMIM:235200
Likely inborn error of metabolism - targeted testing not possible v2.324 ADAR Arina Puzriakova Phenotypes for gene: ADAR were changed from Aicardi-Goutieres syndrome 6 to Aicardi-Goutieres syndrome 6, OMIM:615010; Dyschromatosis symmetrica hereditaria, OMIM:127400
Likely inborn error of metabolism - targeted testing not possible v2.320 ST3GAL3 Sarah Leigh Phenotypes for gene: ST3GAL3 were changed from Intellectual disability; Epileptic encephalopathy, early infantile, 15 615006; ST3GAL3-CDG (Disorders of protein N-glycosylation) 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
Likely inborn error of metabolism - targeted testing not possible v2.315 UQCRC1 Arina Puzriakova Classified gene: UQCRC1 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.315 UQCRC1 Arina Puzriakova Added comment: Comment on list classification: Rating Amber based on current evidence - three unrelated individuals with Parkinson's disease and heterozygous variants identified by one group (PMID: 33141179) but results have failed to be replicated in large European and Chinese cohorts (PMIDs: 33779694; 33248804)
Likely inborn error of metabolism - targeted testing not possible v2.315 UQCRC1 Arina Puzriakova Gene: uqcrc1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.311 PET117 Arina Puzriakova Phenotypes for gene: PET117 were changed from lesions in the medulla oblongata to Mitochondrial complex IV deficiency, nuclear type 19, OMIM:619063
Likely inborn error of metabolism - targeted testing not possible v2.310 NFS1 Arina Puzriakova Classified gene: NFS1 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.310 NFS1 Arina Puzriakova Added comment: Comment on list classification: There is now sufficient evidence to promote this gene to Green at the next GMS review - associated with relevant phenotype in OMIM (MIM#619386) but not yet in G2P. At least one variant reported in six cases from two unrelated families, together with supportive functional studies.
Likely inborn error of metabolism - targeted testing not possible v2.310 NFS1 Arina Puzriakova Gene: nfs1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.306 TWNK Arina Puzriakova Phenotypes for gene: TWNK were changed from Mitochondrial Membrane Protein-Associated Neurodegeneration (biallelic); Disorders of mitochondrial DNA maintenance and integrity; Mitochondrial DNA Depletion Syndrome (biallelic); Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); 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) 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
Likely inborn error of metabolism - targeted testing not possible v2.303 QRSL1 Arina Puzriakova Phenotypes for gene: QRSL1 were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 40, 618835 to Combined oxidative phosphorylation deficiency 40, OMIM:618835
Likely inborn error of metabolism - targeted testing not possible v2.300 POLG2 Arina Puzriakova Phenotypes for gene: POLG2 were changed from Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4,610131; Disorders of mitochondrial DNA maintenance and integrity; Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); 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
Likely inborn error of metabolism - targeted testing not possible v2.299 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
Likely inborn error of metabolism - targeted testing not possible v2.298 UQCRFS1 Arina Puzriakova Classified gene: UQCRFS1 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.298 UQCRFS1 Arina Puzriakova Gene: uqcrfs1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.286 NDUFB10 Arina Puzriakova Classified gene: NDUFB10 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.286 NDUFB10 Arina Puzriakova Gene: ndufb10 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.282 NDUFA8 Arina Puzriakova Classified gene: NDUFA8 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.282 NDUFA8 Arina Puzriakova Gene: ndufa8 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.278 NDUFA13 Arina Puzriakova Classified gene: NDUFA13 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.278 NDUFA13 Arina Puzriakova Gene: ndufa13 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.271 ATP5G3 Arina Puzriakova Classified gene: ATP5G3 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.271 ATP5G3 Arina Puzriakova Gene: atp5g3 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.267 ATP5A1 Arina Puzriakova Publications for gene: ATP5A1 were set to PMID: 23599390 (two siblings with a severe neonatal encephalopathy caused by complex V deficiency); PMID: 23596069 (newborn female with failure to thrive, microcephaly, encephalopathy, IUGR, hypotonia, bacteremia, pulmonary hypertension, heart failure, and mitchondrial depletion).
Likely inborn error of metabolism - targeted testing not possible v2.265 ATP5G3 Arina Puzriakova edited their review of gene: ATP5G3: Added comment: 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 rating should be upgraded from Amber to Green on Mitochondrial panels (R357 and R63). As there is sufficient supporting evidence, the rating should also be updated to Green on this panel at the next GMS review.; Changed rating: GREEN; Changed publications to: 34636445, 34954817; Changed phenotypes to: Dystonia, early-onset, and/or spastic paraplegia, OMIM:619681; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Likely inborn error of metabolism - targeted testing not possible v2.260 STT3A Arina Puzriakova Phenotypes for gene: STT3A were changed from ?Congenital disorder of glycosylation, type Iw 615596 to Congenital disorder of glycosylation, type Iw, autosomal dominant, OMIM:619714; Congenital disorder of glycosylation, type Iw, autosomal recessive, OMIM:615596
Likely inborn error of metabolism - targeted testing not possible v2.254 PRODH Sarah Leigh Classified gene: PRODH as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v2.254 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).
Likely inborn error of metabolism - targeted testing not possible v2.254 PRODH Sarah Leigh Gene: prodh has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.252 TRIT1 Eleanor Williams Phenotypes for gene: TRIT1 were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 35, OMIM:617873 to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 35, OMIM :617873
Likely inborn error of metabolism - targeted testing not possible v2.251 TRIT1 Eleanor Williams Phenotypes for gene: TRIT1 were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis); No OMIM phenotype; Combined oxidative phosphorylation deficiency 35 617873 to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 35, OMIM:617873
Likely inborn error of metabolism - targeted testing not possible v2.249 SLC16A1 Sarah Leigh changed review comment from: Comment on phenotypes: Hyperinsulinemic hypoglycemia, familial, 7;mainly ketosis with borderline reduction in glucose; to: Comment on phenotypes: Previous phenotype entry: Hyperinsulinemic hypoglycemia, familial, 7;mainly ketosis with borderline reduction in glucose
Likely inborn error of metabolism - targeted testing not possible v2.249 SLC16A1 Sarah Leigh Added comment: Comment on phenotypes: Hyperinsulinemic hypoglycemia, familial, 7;mainly ketosis with borderline reduction in glucose
Likely inborn error of metabolism - targeted testing not possible v2.249 SLC16A1 Sarah Leigh Phenotypes for gene: SLC16A1 were changed from Hyperinsulinemic hypoglycemia, familial, 7; mainly ketosis with borderline reduction in glucose to Erythrocyte lactate transporter defect, OMIM:245340; Hyperinsulinemic hypoglycemia, familial, 7, OMIM:610021; Monocarboxylate transporter 1 deficiency, OMIM:616095
Likely inborn error of metabolism - targeted testing not possible v2.248 SETX Sarah Leigh Phenotypes for gene: SETX were changed from Secondary CoQ10 deficiency (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Charcot-Marie-Tooth disease; Hereditary ataxia; Amyotrophic lateral sclerosis/motor neuron disease to Spinocerebellar ataxia, autosomal recessive 1, OMIM:606002; Amyotrophic lateral sclerosis 4, juvenile, OMIM:602433
Likely inborn error of metabolism - targeted testing not possible v2.247 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
Likely inborn error of metabolism - targeted testing not possible v2.247 AFG3L2 Arina Puzriakova Phenotypes for gene: AFG3L2 were changed from Spastic ataxia 5, autosomal recessive OMIM:614487; spastic ataxia 5 MONDO:0013776; Spinocerebellar ataxia 28 OMIM:610246; spinocerebellar ataxia type 28 MONDO:0012450 to Optic atrophy 12, OMIM:618977; Spinocerebellar ataxia 28, OMIM:610246; Spastic ataxia 5, autosomal recessive, OMIM:614487
Likely inborn error of metabolism - targeted testing not possible v2.245 OPA1 Arina Puzriakova Phenotypes for gene: OPA1 were changed from ?Mitochondrial DNA depletion syndrome 14 (encephalocardiomyopathic type) OMIM:616896; mitochondrial DNA depletion syndrome 14 (cardioencephalomyopathic type) MONDO:0014820; Optic atrophy 1 OMIM:165500; autosomal dominant optic atrophy, classic form MONDO:0008134; Optic atrophy plus syndrome OMIM:125250; optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy MONDO:0007429; Behr syndrome OMIM:210000; Behr syndrome MONDO:0008858 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
Likely inborn error of metabolism - targeted testing not possible v2.244 MFN2 Arina Puzriakova Phenotypes for gene: MFN2 were changed from Charcot-Marie-Tooth disease, type 2A2, 609260; Disorders of mitochondrial dynamics, fusion and fission (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of mitochondrial DNA maintenance and integrity; 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
Likely inborn error of metabolism - targeted testing not possible v2.243 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
Likely inborn error of metabolism - targeted testing not possible v2.241 SLC5A6 Arina Puzriakova Phenotypes for gene: SLC5A6 were changed from SLC5A6-related Neurodevelopmental Disorder to Neurodegeneration, infantile-onset, biotin-responsive, OMIM:618973
Likely inborn error of metabolism - targeted testing not possible v2.240 GDAP1 Arina Puzriakova Phenotypes for gene: GDAP1 were changed from Charcot Marie Tooth disease (CMT4A); Charcot-Marie-Tooth disease, type 4A; Charcot-Marie-Tooth disease, axonal, with vocal cord paresis; Charcot-Marie-Tooth disease, recessive intermediate, A; Charcot-Marie-Tooth disease, axonal, type 2K 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
Likely inborn error of metabolism - targeted testing not possible v2.238 PEX6 Sarah Leigh commented on gene: PEX6: For Peroxisome biogenesis disorder 4B (OMIM:614863), Falkenberg et al (PMID: 29220678) has identified Allelic Expression Imbalance (AEI) as a mechanism responsible for the condition. Affected patients (7 unrelated cases) were monoallelic for rs61753230 (c.2578C>T, p.Arg860Trp) and rs144286892 (c.∗442_445 delTAAA), with these variants being on the same chromosome (cis). It would appear that rs144286892 causes the over expression of the allele that it is on, resulting in over expression of rs61753230. The unaffected parents analysed were monoallelic for rs61753230 and biallelic for rs144286892, resulting in overexpression of both rs61753230 and wild type alleles (PMID: 29220678). Experimental evidence revealed that rs61753230 has a dominant-negative effect on the function of the PEX1- PEX6 complex in peroxisomal matrix protein import (PMID: 29220678).
Likely inborn error of metabolism - targeted testing not possible v2.238 PEX6 Sarah Leigh Added comment: Comment on mode of inheritance: The Q1_22_MOI tag has been added to this gene. The mode of inheritance for PEX6 should be 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.
Likely inborn error of metabolism - targeted testing not possible v2.237 PNPT1 Arina Puzriakova Phenotypes for gene: PNPT1 were changed from Deafness, autosomal recessive 70, 614934; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 13, 614932; respiratory chain disorder; hearing loss; Disorders of mitochondrial protein import (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) 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)
Likely inborn error of metabolism - targeted testing not possible v2.232 GATC Sarah Leigh Added comment: Comment on phenotypes: Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
Likely inborn error of metabolism - targeted testing not possible v2.232 GATC Sarah Leigh Phenotypes for gene: GATC were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis) to Combined oxidative phosphorylation deficiency 42, OMIM:618839
Likely inborn error of metabolism - targeted testing not possible v2.221 CPT2 Arina Puzriakova Added comment: Comment on mode of inheritance: MOI should be updated from 'Biallelic' to 'Both mono- and biallelic' at the next GMS review. 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)
Likely inborn error of metabolism - targeted testing not possible v2.218 XPNPEP3 Sarah Leigh edited their review of gene: XPNPEP3: Added comment: Associated with relevant phenotype in OMIM and as limited Gen2Phen gene. At least three variants were reported in three unrelated cases (PMID: 32660933; 20179356). Two of the variants were terminating (RCV000000069, RCV001554332) and the third was a missense variant (RCV000000068), that seems to activate a cryptic splice site; RT-PCR of lymphoblastoid cells showed that this resulted in the inclusion of intronic bases and a frameshift. Cilia-related function was examined by the suppression of zebrafish xpnpep3, resulting in phenotypes reminiscent of ciliopathy morphants, this effect was rescued by human XPNPEP3 that was devoid of a mitochondrial localization signal (PMID: 20179356).; Changed rating: GREEN
Likely inborn error of metabolism - targeted testing not possible v2.218 XPNPEP3 Sarah Leigh Classified gene: XPNPEP3 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.218 XPNPEP3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism - targeted testing not possible v2.218 XPNPEP3 Sarah Leigh Gene: xpnpep3 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.217 XPNPEP3 Sarah Leigh Phenotypes for gene: XPNPEP3 were changed from nephronophthisis-like nephropathy to Nephronophthisis-like nephropathy 1 OMIM:613159; nephronophthisis-like nephropathy 1 MONDO:0013163
Likely inborn error of metabolism - targeted testing not possible v2.214 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
Likely inborn error of metabolism - targeted testing not possible v2.212 SSBP1 Sarah Leigh changed review comment from: Comment on mode of inheritance: The moi for this gene could be changed to BOTH monoallelic and Biallelic as PMID: 34905022 reports a case of SSBP1-disease with biallelic SSBP1 variants.; to: Comment on mode of inheritance: The moi for this gene should be changed to BOTH monoallelic and Biallelic as PMID: 34905022 & 3155024 report two cases of SSBP1-disease associated with biallelic SSBP1 variants. The variant c.380G>A p.(Arg127Gln)(MAF of 0.00004) was found with c.394A>G p.(Ile132Val)(PMID: 34905022), which had previously been found as a homozygote in a single case (PMID: 31550240).
Likely inborn error of metabolism - targeted testing not possible v2.208 TARS2 Sarah Leigh Classified gene: TARS2 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.208 TARS2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism - targeted testing not possible v2.208 TARS2 Sarah Leigh Gene: tars2 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.207 TARS2 Sarah Leigh Phenotypes for gene: TARS2 were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis); ?Combined oxidative phosphorylation deficiency 21, 615918 to Combined oxidative phosphorylation deficiency 21 OMIM:615918; combined oxidative phosphorylation defect type 21 MONDO:0014398
Likely inborn error of metabolism - targeted testing not possible v2.206 TARS2 Sarah Leigh Added comment: Comment on publications: PMID: 24827421 - Compound heterozygous variants in TARS2 were reported in the proband and his affected sister - a missense mutation (c.845C>T, p.Pro282Leu) and a nucleotide change in position +3 of intron 6 (g.4255A>G, c.695+3A>G). The parents carrying one of the variants, one unaffected sister carried one variant, and the other unaffected sibling carried neither.
Likely inborn error of metabolism - targeted testing not possible v2.206 TARS2 Sarah Leigh Publications for gene: TARS2 were set to PMID: 24827421 - Compound heterozygous variants in TARS2 were reported in the proband and his affected sister - a missense mutation (c.845C>T, p.Pro282Leu) and a nucleotide change in position +3 of intron 6 (g.4255A>G, c.695+3A>G). The parents carrying one of the variants, one unaffected sister carried one variant, and the other unaffected sibling carried neither.
Likely inborn error of metabolism - targeted testing not possible v2.204 SLC30A10 Arina Puzriakova Phenotypes for gene: SLC30A10 were changed from Parkinson Disease and Complex Parkinsonism; Early onset dystonia; Hypermanganesemia with dystonia 1; Hypermanganesemia with dystonia, polycythemia, and cirrhosis (Disorder of magnesium metabolism) to Hypermanganesemia with dystonia 1, OMIM:613280
Likely inborn error of metabolism - targeted testing not possible v2.201 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
Likely inborn error of metabolism - targeted testing not possible v2.198 CLPB Arina Puzriakova Added comment: Comment on mode of inheritance: MOI should be updated from 'Biallelic' to 'Both mono- and biallelic' at the next GMS update.

Wortmann et al. 2021 (PMID: 34140661) published six unrelated individuals with one of four different de novo monoallelic missense variants in CLPB. The phenotype overlapped with that observed in the recessive disease including neurodevelopmental delay, seizures, 3-MGA-uria, and neutropenia. Some functional studies of heterozygous variants were performed.
Likely inborn error of metabolism - targeted testing not possible v2.197 CLPB Arina Puzriakova Phenotypes for gene: CLPB were changed from 3-methylglutaconic aciduria with the following: cataract, renal cysts and nephrocalcinosis; cataract, neutropenia, epilepsy; congenital microcephaly and severe encephalopathy; progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder to 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, OMIM:616271
Likely inborn error of metabolism - targeted testing not possible v2.196 FXN Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: FXN.
Likely inborn error of metabolism - targeted testing not possible v2.196 GLS_GCA Arina Puzriakova Phenotypes for STR: GLS_GCA were changed from Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733 to Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412
Likely inborn error of metabolism - targeted testing not possible v2.195 GLS Arina Puzriakova commented on gene: GLS: Added 'watchlist_MOI' tag to highlight monoallelic phenotype (MIM# 618339) which is also relevant to this panel, but as there is only a single case reported to date this is not yet sufficient to update the MOI.
Likely inborn error of metabolism - targeted testing not possible v2.195 GLS Arina Puzriakova Phenotypes for gene: GLS were changed from Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733; Developmental and epileptic encephalopathy 71, OMIM:618328; Developmental and epileptic encephalopathy, 71, MONDO:0032678; ?Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, OMIM:618339; Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, MONDO:0032685 to Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Developmental and epileptic encephalopathy 71, OMIM:618328; ?Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, OMIM:618339
Likely inborn error of metabolism - targeted testing not possible v2.193 CSTB Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: CSTB.
Likely inborn error of metabolism - targeted testing not possible v2.193 CSTB Arina Puzriakova Phenotypes for gene: CSTB were changed from Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) 254800 to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), OMIM:254800
Likely inborn error of metabolism - targeted testing not possible v2.191 ATXN7 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Likely inborn error of metabolism - targeted testing not possible v2.190 ATXN7 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATXN7.
Tag currently-ngs-unreportable tag was added to gene: ATXN7.
Likely inborn error of metabolism - targeted testing not possible v2.187 EHHADH Arina Puzriakova Classified gene: EHHADH as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.187 EHHADH Arina Puzriakova Added comment: Comment on list classification: Single family reported with additional functional data which is sufficient evidence to rate as Amber, awaiting further evidence.
Likely inborn error of metabolism - targeted testing not possible v2.187 EHHADH Arina Puzriakova Gene: ehhadh has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.186 EHHADH Arina Puzriakova Phenotypes for gene: EHHADH were changed from L-bifunctional protein deficiency; Metabolic acidosis; Increased amino acids in urine to ?Fanconi renotubular syndrome 3, OMIM:615605; L-bifunctional protein deficiency; Metabolic acidosis; Increased amino acids in urine
Likely inborn error of metabolism - targeted testing not possible v2.181 ACAT2 Arina Puzriakova Classified gene: ACAT2 as Red List (low evidence)
Likely inborn error of metabolism - targeted testing not possible v2.181 ACAT2 Arina Puzriakova Added comment: Comment on list classification: New gene added by Andžela Lazdāne. Currently associated with a provisional phenotype in OMIM (?ACAT2 deficiency, OMIM:614055) and not yet listed in G2P. In the 2 cases reported to date (PMIDs: 20597, 6150136), diagnoses were made based on molecular rather than genetic findings. Rating Red as at present there is no published evidence of deleterious variants in the ACAT2 gene leading to this phenotype.
Likely inborn error of metabolism - targeted testing not possible v2.181 ACAT2 Arina Puzriakova Gene: acat2 has been classified as Red List (Low Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.180 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
Likely inborn error of metabolism - targeted testing not possible v2.175 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); Spastic paraplegia 55, autosomal recessive, 615035; Combined oxidative phosphorylation deficiency 7, 613559 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)
Likely inborn error of metabolism - targeted testing not possible v2.174 SERAC1 Arina Puzriakova Phenotypes for gene: SERAC1 were changed from Disorders of mitochondrial membrane lipids (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Methylglutaconic aciduria with deafness, encephalopathy and Leigh-like syndrome (MEGDEL) (Organic acidurias); 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)
Likely inborn error of metabolism - targeted testing not possible v2.173 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
Likely inborn error of metabolism - targeted testing not possible v2.167 PIGS Arina Puzriakova gene: PIGS was added
gene: PIGS was added to Inborn errors of metabolism. Sources: Expert Review Amber,Expert list
for-review tags were added to gene: PIGS.
Mode of inheritance for gene: PIGS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGS were set to 30269814
Phenotypes for gene: PIGS were set to Glycosylphosphatidylinositol biosynthesis defect 18 618143
Likely inborn error of metabolism - targeted testing not possible v2.166 GMPPA Arina Puzriakova gene: GMPPA was added
gene: GMPPA was added to Inborn errors of metabolism. Sources: Expert Review Amber,Expert list
for-review tags were added to gene: GMPPA.
Mode of inheritance for gene: GMPPA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GMPPA were set to 24035193; 28574218
Phenotypes for gene: GMPPA were set to Alacrima, achalasia, and mental retardation syndrome (MIM# 615510)
Likely inborn error of metabolism - targeted testing not possible v2.161 CSGALNACT1 Arina Puzriakova gene: CSGALNACT1 was added
gene: CSGALNACT1 was added to Inborn errors of metabolism. Sources: Expert list,Expert Review Amber
for-review tags were added to gene: CSGALNACT1.
Mode of inheritance for gene: CSGALNACT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSGALNACT1 were set to 31705726; 31325655; 31705726
Phenotypes for gene: CSGALNACT1 were set to Congenital disorder of glycosylation; Skeletal dysplasia, mild, with joint laxity and advanced bone age OMIM:618870; skeletal dysplasia, mild, with joint laxity and advanced bone age MONDO:0030029
Likely inborn error of metabolism - targeted testing not possible v2.160 B4GALNT1 Arina Puzriakova gene: B4GALNT1 was added
gene: B4GALNT1 was added to Inborn errors of metabolism. Sources: Expert Review Amber,Expert list
Q2_21_rating tags were added to gene: B4GALNT1.
Mode of inheritance for gene: B4GALNT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B4GALNT1 were set to 23746551; 24103911
Phenotypes for gene: B4GALNT1 were set to Spastic paraplegia 26, autosomal recessive, OMIM:609195; Hereditary spastic paraplegia 26, MONDO:0012213
Likely inborn error of metabolism - targeted testing not possible v2.158 APOA1 Sarah Leigh Phenotypes for gene: APOA1 were changed from Corneal clouding, autosomal recessive; Apolipoprotein A-I deficiency (Disorders of high density lipoprotein metabolism); ApoA-I and apoC-III deficiency, combined; Amyloidosis, 3 or more types 105200; 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
Likely inborn error of metabolism - targeted testing not possible v2.156 COQ2 Ivone Leong Added comment: Comment on phenotypes: Previously:
{Multiple system atrophy, susceptibility to}, 146500;Coenzyme Q10 deficiency;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
Likely inborn error of metabolism - targeted testing not possible v2.156 COQ2 Ivone Leong Phenotypes for gene: COQ2 were changed from {Multiple system atrophy, susceptibility to}, 146500; Coenzyme Q10 deficiency; 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 to Coenzyme Q10 deficiency, primary, 1, OMIM:607426
Likely inborn error of metabolism - targeted testing not possible v2.154 EHHADH Andžela Lazdāne gene: EHHADH was added
gene: EHHADH was added to Inborn errors of metabolism. Sources: Literature
Mode of inheritance for gene: EHHADH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EHHADH were set to PMID: 33340416
Phenotypes for gene: EHHADH were set to L-bifunctional protein deficiency; Metabolic acidosis; Increased amino acids in urine
Review for gene: EHHADH was set to AMBER
Added comment: Fanconi renotubular syndrome type 3.
The EHHADH gene is included in international classification of inherited metabolic disorders (ICIMD), Disorders of peroxisomal fatty acid oxidation.
IEM Nosology Group (IEMbase): Disorders of peroxisomal β-oxidation.
Sources: Literature
Likely inborn error of metabolism - targeted testing not possible v2.154 IDH1 Andžela Lazdāne gene: IDH1 was added
gene: IDH1 was added to Inborn errors of metabolism. Sources: Literature
Mode of inheritance for gene: IDH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IDH1 were set to PMID: 33340416
Phenotypes for gene: IDH1 were set to Failure to thrive; Psychomotor delay; Feeding difficulties; Increased D-2-Hydroxyglutaric acid in urine
Review for gene: IDH1 was set to AMBER
Added comment: Isocitrate dehydrogenase 1 deficiency.

IEM Nosology Group (IEMbase):Disorders of the Krebs cycle. The IDH1 gene is included in International classification of inherited metabolic disorders (ICIMD), Disorders of the Krebs cycle.
Sources: Literature
Likely inborn error of metabolism - targeted testing not possible v2.154 ACAT2 Andžela Lazdāne commented on gene: ACAT2: ACAT2 gene is included in international classification of inherited metabolic
disorders (ICIMD).
Likely inborn error of metabolism - targeted testing not possible v2.153 PEX6 Sarah Leigh Phenotypes for gene: PEX6 were changed from Disorders of peroxisome biogenesis; Peroxisome biogenesis disorder 4B 614863; Peroxisome biogenesis disorder 4A (Zellweger) 614862 to Peroxisome biogenesis disorder 4A (Zellweger) OMIM:614862; peroxisome biogenesis disorder 4A (Zellweger) MONDO:0013930; Peroxisome biogenesis disorder 4B OMIM:614863; peroxisome biogenesis disorder 4B MONDO:0013931
Likely inborn error of metabolism - targeted testing not possible v2.152 PEX6 Sarah Leigh reviewed gene: PEX6: Rating: GREEN; Mode of pathogenicity: None; Publications: 29220678, 20301621; Phenotypes: Peroxisome biogenesis disorder 4A (Zellweger) OMIM:614862, peroxisome biogenesis disorder 4A (Zellweger) MONDO:0013930, Peroxisome biogenesis disorder 4B OMIM:614863, peroxisome biogenesis disorder 4B MONDO:0013931; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Likely inborn error of metabolism - targeted testing not possible v2.152 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
Likely inborn error of metabolism - targeted testing not possible v2.150 ATAD3A Arina Puzriakova Phenotypes for gene: ATAD3A were changed from Harel-Yoon syndrome 617183 to Harel-Yoon syndrome, OMIM:617183; Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal, OMIM:618810; Lactic acidosis; Methylglutaconic aciduria
Likely inborn error of metabolism - targeted testing not possible v2.144 FAR1 Arina Puzriakova Classified gene: FAR1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v2.144 FAR1 Arina Puzriakova Added comment: Comment on list classification: In view of the normal metabolic screening (excluding very specific functional work, which will not be in routine NHS practice) there is no clear alignment with the metabolic panels and therefore FAR1 should be demoted from Green to Red at the next GMS panel update (discussed with Helen Brittain, Genomic England Clinical Team)
Likely inborn error of metabolism - targeted testing not possible v2.144 FAR1 Arina Puzriakova Gene: far1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.142 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
Likely inborn error of metabolism - targeted testing not possible v2.141 NAXD Ivone Leong gene: NAXD was added
gene: NAXD was added to Inborn errors of metabolism. Sources: Expert Review Amber,Expert list
Q2_21_rating tags were added to gene: NAXD.
Mode of inheritance for gene: NAXD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAXD were set to 30576410; 33224489; 31755961
Phenotypes for gene: NAXD were set to Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2, OMIM:618321
Likely inborn error of metabolism - targeted testing not possible v2.138 NFU1 Arina Puzriakova Phenotypes for gene: NFU1 were changed from Multiple mitochondrial dysfunctions syndrome 1; Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) to Multiple mitochondrial dysfunctions syndrome 1, OMIM:605711; Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only))
Likely inborn error of metabolism - targeted testing not possible v2.137 NAXE Arina Puzriakova Phenotypes for gene: NAXE were changed from Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy 617186 to Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, OMIM:617186
Likely inborn error of metabolism - targeted testing not possible v2.136 ABCB7 Sarah Leigh Added comment: Comment on phenotypes: Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only));congenital cerebellar hypoplasia/atrophy (PMID: 26242992).;Disorders of iron homeostasis
Likely inborn error of metabolism - targeted testing not possible v2.136 ABCB7 Sarah Leigh Phenotypes for gene: ABCB7 were changed from Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); congenital cerebellar hypoplasia/atrophy (PMID: 26242992).; Anemia, sideroblastic, with ataxia; Disorders of iron homeostasis to Anemia, sideroblastic, with ataxia OMIM:301310; X-linked sideroblastic anemia with ataxia MONDO:0010524
Likely inborn error of metabolism - targeted testing not possible v2.135 AFG3L2 Sarah Leigh Added comment: Comment on phenotypes: Ataxia, spastic, 5, autosomal recessive, 614487;Miscellaneous disorders/unknown function (Mitochondrial respiratory chain disorders (caused by nuclear variants only));Spinocerebellar ataxia 28, 610246;Disorders of mitochondrial DNA maintenance and integrity
Likely inborn error of metabolism - targeted testing not possible v2.135 AFG3L2 Sarah Leigh Phenotypes for gene: AFG3L2 were changed from Ataxia, spastic, 5, autosomal recessive, 614487; Miscellaneous disorders/unknown function (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Spinocerebellar ataxia 28, 610246; Disorders of mitochondrial DNA maintenance and integrity to Spastic ataxia 5, autosomal recessive OMIM:614487; spastic ataxia 5 MONDO:0013776; Spinocerebellar ataxia 28 OMIM:610246; spinocerebellar ataxia type 28 MONDO:0012450
Likely inborn error of metabolism - targeted testing not possible v2.132 FXN Sarah Leigh Added comment: Comment on phenotypes: Friedreich ataxia, 229300;Friedreich ataxia with retained reflexes, 229300;Hereditary ataxia;Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only))
Likely inborn error of metabolism - targeted testing not possible v2.132 FXN Sarah Leigh Phenotypes for gene: FXN were changed from Friedreich ataxia, 229300; Friedreich ataxia with retained reflexes, 229300; Hereditary ataxia; 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; Friedreich ataxia 1 MONDO:0100340
Likely inborn error of metabolism - targeted testing not possible v2.127 OPA1 Sarah Leigh Added comment: Comment on phenotypes: Optic atrophy plus syndrome, 125250;{Glaucoma, normal tension, susceptibility to}, 606657;Disorders of mitochondrial DNA maintenance and integrity;Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions;Optic atrophy 1, 165500;Mitochondrial DNA Depletion Syndrome;Disorders of mitochondrial dynamics, fusion and fission (Mitochondrial respiratory chain disorders (caused by nuclear variants only))
Likely inborn error of metabolism - targeted testing not possible v2.127 OPA1 Sarah Leigh Phenotypes for gene: OPA1 were changed from Optic atrophy plus syndrome, 125250; {Glaucoma, normal tension, susceptibility to}, 606657; Disorders of mitochondrial DNA maintenance and integrity; Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions; Optic atrophy 1, 165500; Mitochondrial DNA Depletion Syndrome; Disorders of mitochondrial dynamics, fusion and fission (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) to ?Mitochondrial DNA depletion syndrome 14 (encephalocardiomyopathic type) OMIM:616896; mitochondrial DNA depletion syndrome 14 (cardioencephalomyopathic type) MONDO:0014820; Optic atrophy 1 OMIM:165500; autosomal dominant optic atrophy, classic form MONDO:0008134; Optic atrophy plus syndrome OMIM:125250; optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy MONDO:0007429; Behr syndrome OMIM:210000; Behr syndrome MONDO:0008858
Likely inborn error of metabolism - targeted testing not possible v2.124 NDUFB7 Sarah Leigh Phenotypes for gene: NDUFB7 were changed from No OMIM phenotype; Isolated complex I deficiency to Congenital lactic acidosis; hypertrophic cardiomyopathy
Likely inborn error of metabolism - targeted testing not possible v2.122 NDUFB7 Sarah Leigh Classified gene: NDUFB7 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.122 NDUFB7 Sarah Leigh Added comment: Comment on list classification: Comment on list classification: Not associated with relevant phenotype in OMIM or Gen2Phen. At least one biallelic splicing variant reported. RNA sequencing revealed that this variant disrupted normal splicing (PMID 33502047) and human knock-out cells have shown that NDUFB7 is one of the subunits strictly required for assembly of a functional mitochondrial complex I subunit, which is essential for cell viability (PMID 27626371).
Likely inborn error of metabolism - targeted testing not possible v2.122 NDUFB7 Sarah Leigh Gene: ndufb7 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.116 NDUFA12 Sarah Leigh Classified gene: NDUFA12 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.116 NDUFA12 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism - targeted testing not possible v2.116 NDUFA12 Sarah Leigh Gene: ndufa12 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.110 FBXL4 Sarah Leigh Added comment: Comment on phenotypes: fatal encephalopathy, lactic acidosis, and severe MTDNA depletion in muscle.;Disorders of mitochondrial DNA maintenance and integrity
Likely inborn error of metabolism - targeted testing not possible v2.110 FBXL4 Sarah Leigh Phenotypes for gene: FBXL4 were changed from fatal encephalopathy, lactic acidosis, and severe MTDNA depletion in muscle.; Disorders of mitochondrial DNA maintenance and integrity; Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type), 615471 to Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) OMIM:615471; mitochondrial DNA depletion syndrome 13 MONDO:0014198
Likely inborn error of metabolism - targeted testing not possible v2.109 COA7 Sarah Leigh Phenotypes for gene: COA7 were changed from to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 OMIM:618387; spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 MONDO:0020770
Likely inborn error of metabolism - targeted testing not possible v2.107 LARS2 Arina Puzriakova Phenotypes for gene: LARS2 were changed from Perrault syndrome; Perrault syndrome 4, 615300; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) 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
Likely inborn error of metabolism - targeted testing not possible v2.106 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
Likely inborn error of metabolism - targeted testing not possible v2.103 GNE Sarah Leigh Added comment: Comment on phenotypes: Nonaka myopathy 605820;Sialuria (Other lysosomal disorders);UDP-GlcNAc epimerase/kinase deficiency (Disorders of multiple glycosylation and other glycosylation pathways);ADUDP-GlcNAc epimerase/kinase deficiency (Disorders of multiple glycosylation and other glycosylation pathways)
Likely inborn error of metabolism - targeted testing not possible v2.103 GNE Sarah Leigh Phenotypes for gene: GNE were changed from Nonaka myopathy 605820; Sialuria (Other lysosomal disorders); UDP-GlcNAc epimerase/kinase deficiency (Disorders of multiple glycosylation and other glycosylation pathways); 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
Likely inborn error of metabolism - targeted testing not possible v2.66 NDUFC2 Sarah Leigh Classified gene: NDUFC2 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.66 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.
Likely inborn error of metabolism - targeted testing not possible v2.66 NDUFC2 Sarah Leigh Gene: ndufc2 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.65 NDUFC2 Sarah Leigh edited their review of gene: NDUFC2: Added comment: 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).; Changed rating: GREEN
Likely inborn error of metabolism - targeted testing not possible v2.64 NDUFC2 Sarah Leigh Added comment: Comment on phenotypes: Assigned a phenotype by OMIM 02/02/2021
Likely inborn error of metabolism - targeted testing not possible v2.63 POMK Sarah Leigh Classified gene: POMK as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.63 POMK Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism - targeted testing not possible v2.63 POMK Sarah Leigh Gene: pomk has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.56 GORAB Sarah Leigh Classified gene: GORAB as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.56 GORAB Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Likely inborn error of metabolism - targeted testing not possible v2.56 GORAB Sarah Leigh Gene: gorab has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.54 TRAPPC11 Sarah Leigh Phenotypes for gene: TRAPPC11 were changed from Muscular dystrophy, limb-girdle, autosomal recessive 18 OMIM:615356; autosomal recessive limb-girdle muscular dystrophy type 2S MONDO:0014144 to Muscular dystrophy, limb-girdle, autosomal recessive 18 OMIM:615356; autosomal recessive limb-girdle muscular dystrophy type 2S MONDO:0014144
Likely inborn error of metabolism - targeted testing not possible v2.53 TRAPPC11 Sarah Leigh Phenotypes for gene: TRAPPC11 were changed from Muscular dystrophy, limb-girdle, type 2S to Muscular dystrophy, limb-girdle, autosomal recessive 18 OMIM:615356; autosomal recessive limb-girdle muscular dystrophy type 2S MONDO:0014144
Likely inborn error of metabolism - targeted testing not possible v2.52 TRAPPC11 Sarah Leigh Classified gene: TRAPPC11 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.52 TRAPPC11 Sarah Leigh Gene: trappc11 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.51 AASS Zornitza Stark reviewed gene: AASS: Rating: AMBER; Mode of pathogenicity: None; Publications: 23570448; Phenotypes: Hyperlysinemia, MIM# 238700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism - targeted testing not possible v2.51 POMK Zornitza Stark gene: POMK was added
gene: POMK was added to Inborn errors of metabolism. Sources: Expert Review
Mode of inheritance for gene: POMK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POMK were set to 23519211; 24556084; 24925318
Phenotypes for gene: POMK were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 12 (MIM #615249)
Review for gene: POMK was set to GREEN
gene: POMK was marked as current diagnostic
Added comment: Other enzyme deficiencies causing dystroglycanopathies are included in the panel.
Sources: Expert Review
Likely inborn error of metabolism - targeted testing not possible v2.51 MSMO1 Arina Puzriakova Phenotypes for gene: MSMO1 were changed from Sterol-C4-methyl oxidase deficiency (Disorders of sterol biosynthesis); (SC4MOL DEFICIENCY); Microcephaly, congenital cataract, and psoriasiform dermatitis, 616834 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
Likely inborn error of metabolism - targeted testing not possible v2.50 GLS_GCA Arina Puzriakova Classified STR: GLS_GCA as Red List (low evidence)
Likely inborn error of metabolism - targeted testing not possible v2.50 GLS_GCA Arina Puzriakova Added comment: Comment on list classification: There are sufficient unrelated cases and supportive functional data for inclusion as diagnostic-grade.

However, detection of this 5' UTR triplet expansion must first be validated within the Genomics England pipeline. In the meantime, rating Red but will raise the STR for validation with the Rare Disease team.
Likely inborn error of metabolism - targeted testing not possible v2.50 GLS_GCA Arina Puzriakova Str: gls_gca has been classified as Red List (Low Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.49 GLS_GCA Arina Puzriakova STR: GLS_GCA was added
STR: GLS_GCA was added to Inborn errors of metabolism. Sources: Literature
STR, NGS Not Validated, for-review tags were added to STR: GLS_GCA.
Mode of inheritance for STR: GLS_GCA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for STR: GLS_GCA were set to 30970188
Phenotypes for STR: GLS_GCA were set to Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733
Review for STR: GLS_GCA was set to GREEN
Added comment: GLS is associated with relevant phenotypes in OMIM, but currently is not in Gene2Phenoype.
----------

- PMID: 30970188 (2019) - Three unrelated cases who presented with an early-onset global developmental delay, progressive ataxia, and elevated levels of glutamine (MIM# 618412). One patient also showed cerebellar atrophy.

All 3 individuals harboured a large trinucleotide (GCA) repeat expansion in the 5' UTR (length: 680-1,500-copy repeats). The repeat expansion was found in homozygosity in 1 case, and occurred in compound heterozygosity with an SNV in the other two cases (missense and frameshift variant, respectively). Functional analysis showed the repeat expansion results in reduced expression and glutaminase deficiency.
Sources: Literature
Likely inborn error of metabolism - targeted testing not possible v2.48 GLS Arina Puzriakova Classified gene: GLS as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v2.48 GLS Arina Puzriakova Added comment: Comment on list classification: There are sufficient cases, supported by functional data, to rate this gene Green - however, detection of the 5' UTR triplet expansion (PMID:30970188) has not yet been validated within the Genomics England pipeline.

When excluding cases with the STR, the remaining evidence is not sufficient for inclusion as diagnostic-grade and therefore this gene is tagged 'for-review' to assess whether it should be downgraded to Amber until the STR is validated or additional cases arise.
Likely inborn error of metabolism - targeted testing not possible v2.48 GLS Arina Puzriakova Gene: gls has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.47 GLS Arina Puzriakova Phenotypes for gene: GLS were changed from Glucosidase 1 deficiency (Disorders of protein N-glycosylation); Epileptic encephalopathy, early infantile, 71 618328; Global developmental delay, progressive ataxia, and elevated glutamine 618412 to Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412; Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733; Developmental and epileptic encephalopathy 71, OMIM:618328; Developmental and epileptic encephalopathy, 71, MONDO:0032678; ?Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, OMIM:618339; Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, MONDO:0032685
Likely inborn error of metabolism - targeted testing not possible v2.44 GLS Arina Puzriakova reviewed gene: GLS: Rating: ; Mode of pathogenicity: None; Publications: 30970188, 30575854, 30239721; Phenotypes: Global developmental delay, progressive ataxia, and elevated glutamine, OMIM:618412, Global developmental delay, progressive ataxia, and elevated glutamine, MONDO:0032733, Developmental and epileptic encephalopathy 71, OMIM:618328, Developmental and epileptic encephalopathy, 71, MONDO:0032678, ?Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, OMIM:618339, Infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development, MONDO:0032685; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism - targeted testing not possible v2.44 NUS1 Eleanor Williams Classified gene: NUS1 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.44 NUS1 Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber on advice from Genomics England clinical team. 1 case plus some functional data.
Likely inborn error of metabolism - targeted testing not possible v2.44 NUS1 Eleanor Williams Gene: nus1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.41 NUS1 Eleanor Williams edited their review of gene: NUS1: Added comment: Provisionally associated with ?Congenital disorder of glycosylation, type 1aa #617082 (AR) in OMIM based on family reported in Park et al 2014 (PMID: 25066056). They describe a family of Roma origin in which 2 out of 4 siblings presented with congenital scoliosis, severe neurological impairment, refractory epilepsy, hearing deficit and visual impairment with discrete bilateral macular lesions. A homozgyous missense mutation, R290H, was found in NUS1 (called NGBR in the paper) by exome sequencing. It segregated with the disease in the family. Patient fibroblasts showed reduced dolichol profiles and enhanced accumulation of free cholesterol as do fibroblasts from mice lacking NgBR.; Changed publications: 25066056; Changed phenotypes: ?Congenital disorder of glycosylation, type 1aa OMIM:617082, congenital disorder of glycosylation, type IAA MONDO:0014904
Likely inborn error of metabolism - targeted testing not possible v2.39 SHMT2 Arina Puzriakova Classified gene: SHMT2 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.39 SHMT2 Arina Puzriakova Gene: shmt2 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.38 SHMT2 Arina Puzriakova Classified gene: SHMT2 as Red List (low evidence)
Likely inborn error of metabolism - targeted testing not possible v2.38 SHMT2 Arina Puzriakova Added comment: Comment on list classification: New gene added as Amber but can be promoted to Green at the next GMS panel update (added 'for-review' tag)
Likely inborn error of metabolism - targeted testing not possible v2.38 SHMT2 Arina Puzriakova Gene: shmt2 has been classified as Red List (Low Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.37 SHMT2 Arina Puzriakova gene: SHMT2 was added
gene: SHMT2 was added to Inborn errors of metabolism. Sources: Literature
for-review tags were added to gene: SHMT2.
Mode of inheritance for gene: SHMT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SHMT2 were set to 33015733
Phenotypes for gene: SHMT2 were set to Neurodevelopmental disorder with cardiomyopathy, spasticity, and brain abnormalities, OMIM:619121
Review for gene: SHMT2 was set to GREEN
Added comment: PMID: 33015733 (2020) - 5 individuals from 4 families with a novel brain and heart developmental syndrome caused by biallelic SHMT2 pathogenic variants.

Clinical features include dysmorphism, congenital microcephaly, hypertrophic cardiomyopathy or atrial-septal defects, DD/ID and motor dysfunction, in the form of spastic paraparesis, ataxia, and/or peripheral neuropathy.

SHMT2 encodes the mitochondrial form of serine hydroxymethyltransferase. The enzyme transfers one-carbon units from serine to tetrahydrofolate (THF) and generates glycine and 5,10,methylene-THF.

While plasma metabolites were within normal range and SHMT2 protein levels not significantly altered in patient fibroblasts, the authors provide evidence for impaired enzymatic function eg. presence of the SHMT2 substrate (THF) in patient but not control (mitochondria-enriched) fibroblasts, decrease in glycine/serine ratios, impaired folate metabolism. Patient fibroblasts displayed impaired oxidative capacity (reduced ATP levels in a medium without glucose, diminished oxygen consumption rates). Mitochondrial membrane potential and ROS levels were also suggestive of redox malfunction.
Sources: Literature
Likely inborn error of metabolism - targeted testing not possible v2.36 HS2ST1 Ivone Leong Classified gene: HS2ST1 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.36 HS2ST1 Ivone Leong Gene: hs2st1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.35 HS2ST1 Ivone Leong gene: HS2ST1 was added
gene: HS2ST1 was added to Inborn errors of metabolism. Sources: Literature
for-review tags were added to gene: HS2ST1.
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 AMBER
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. This gene should be considered for Green gene rating status at the next review.
Sources: Literature
Likely inborn error of metabolism - targeted testing not possible v2.34 AASS Arina Puzriakova Phenotypes for gene: AASS were changed from Intellectual disability; Hyperlysinemia; Hyperlysinaemia (Disorders of histidine, tryptophan or lysine metabolism) to Hyperlysinemia, OMIM:238700; Hyperlysinemia (disease), MONDO:0009388
Likely inborn error of metabolism - targeted testing not possible v2.26 GALM Ivone Leong Classified gene: GALM as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.26 GALM Ivone Leong Gene: galm has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.25 GALM Ivone Leong gene: GALM was added
gene: GALM was added to Inborn errors of metabolism. Sources: Expert Review,Literature
for-review tags were added to gene: GALM.
Mode of inheritance for gene: GALM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GALM were set to 30451973; 30910422
Phenotypes for gene: GALM were set to Galactosemia IV, 618881
Review for gene: GALM was set to GREEN
Added comment: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with an appropriate phenotype in OMIM but not in Gene2Phenotype. There is enough evidence for this gene to be Green. The gene has been given an Amber rating and will be promoted to Green at the next review.

Review from Zornitza Stark (Australian Genomics) on the Cholestasis panel:
Homozygous and compound heterozygous variants (missense, nonsense and frameshift) found in 8 Japanese patients from unrelated families with unexplained galactosaemia. (No variants in GALT, GALK1, and GALE). In vitro expression analysis and enzyme activity assay of the patients’ peripheral blood mononuclear cells showed total lack of or compromised expression of GALM protein. One homozygote for one of these variants p.(Gly142Arg) in gnomAD (African population). (Wada, Y. et al 2019; PMID: 30451973) Note only two individuals were reported as having transient cholestasis. Sources: Literature
Zornitza Stark (Australian Genomics), 2 May 2020
Sources: Expert Review, Literature
Likely inborn error of metabolism - targeted testing not possible v2.24 SLC5A6 Sarah Leigh changed review comment from: Comment on list classification: Based on five variants in three unrelated cases, together with supportive aminal model studies.; to: Comment on list classification: Based on five variants in three unrelated cases, together with supportive animal model studies.
Likely inborn error of metabolism - targeted testing not possible v2.24 SLC5A6 Arina Puzriakova Classified gene: SLC5A6 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.24 SLC5A6 Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Likely inborn error of metabolism - targeted testing not possible v2.24 SLC5A6 Arina Puzriakova Gene: slc5a6 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.23 XYLT1 Arina Puzriakova Phenotypes for gene: XYLT1 were changed from Desbuquois dysplasia 2 to Desbuquois dysplasia 2, 615777
Likely inborn error of metabolism - targeted testing not possible v2.21 AHCY Arina Puzriakova Classified gene: AHCY as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.21 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.
Likely inborn error of metabolism - targeted testing not possible v2.21 AHCY Arina Puzriakova Gene: ahcy has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.21 AHCY Arina Puzriakova Classified gene: AHCY as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.21 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.
Likely inborn error of metabolism - targeted testing not possible v2.21 AHCY Arina Puzriakova Gene: ahcy has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.20 AHCY Arina Puzriakova Classified gene: AHCY as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.20 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.
Likely inborn error of metabolism - targeted testing not possible v2.20 AHCY Arina Puzriakova Gene: ahcy has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.20 AHCY Arina Puzriakova Classified gene: AHCY as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.20 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 due to variants in AHCY.
Likely inborn error of metabolism - targeted testing not possible v2.20 AHCY Arina Puzriakova Gene: ahcy has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.17 TKFC Arina Puzriakova Classified gene: TKFC as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.17 TKFC Arina Puzriakova Added comment: Comment on list classification: Additional cases required before inclusion on a diagnostic panel (added to watchlist).
Likely inborn error of metabolism - targeted testing not possible v2.17 TKFC Arina Puzriakova Gene: tkfc has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.16 TKFC Arina Puzriakova gene: TKFC was added
gene: TKFC was added to Inborn errors of metabolism. Sources: Literature
watchlist tags were added to gene: TKFC.
Mode of inheritance for gene: TKFC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TKFC were set to 32004446
Phenotypes for gene: TKFC were set to Triokinase and FMN cyclase deficiency syndrome, 618805
Review for gene: TKFC was set to AMBER
Added comment: Associated with phenotype in OMIM, and a possible gene for TKFC-related Cataracts and Multisystem Disease in G2P.

PMID: 32004446 (2020) - Two sib pairs from two unrelated consanguineous families with an inborn error of metabolism caused by distinct homozygous variants in TKFC. In Family 1, both sibs had congenital cataracts but otherwise presented disparate phenotypes. The older sister had DD (motor and speech) and cerebellar hypoplasia; while the younger sister had liver dysfunction and fatal cardiomyopathy at 11 weeks with severe lactic acidosis following a febrile illness. In Family 2, the brother exhibited global DD as well as bilateral cataracts at 22 months. He developed progressive non-cholestatic liver failure, and at 3yrs-10months he could not walk independently and had no words. His older sister, had delayed speech development and learning difficulties, but is otherwise well and did not have cataracts.

Both variants segregated with disease in each family, and some functional data of the variants using yeast cells.
Sources: Literature
Likely inborn error of metabolism - targeted testing not possible v2.14 ALG14 Sarah Leigh Classified gene: ALG14 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v2.14 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.
Likely inborn error of metabolism - targeted testing not possible v2.14 ALG14 Sarah Leigh Gene: alg14 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.10 SLC5A6 Sarah Leigh Classified gene: SLC5A6 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v2.10 SLC5A6 Sarah Leigh Added comment: Comment on list classification: Based on five variants in three unrelated cases, together with supportive aminal model studies.
Likely inborn error of metabolism - targeted testing not possible v2.10 SLC5A6 Sarah Leigh Gene: slc5a6 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v2.9 SLC5A6 Sarah Leigh gene: SLC5A6 was added
gene: SLC5A6 was added to Inborn errors of metabolism. Sources: Literature
Mode of inheritance for gene: SLC5A6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC5A6 were set to 27904971; 31392107; 31754459; 23104561; 29669219
Phenotypes for gene: SLC5A6 were set to SLC5A6-related Neurodevelopmental Disorder
Review for gene: SLC5A6 was set to GREEN
Added comment: Not associated with phenotype in OMIM and as possible Gen2Phen gene for SLC5A6-related Neurodevelopmental Disorder. At least 5 variants published in three unrelated famililies (4 cases total) with SLC5A6-related Neurodevelopmental Disorder, together with supportive functional studies (PMID 29669219; 23104561). One of the cases had mixed semiology seizures including focal dyscognitive, absence, tonic spasms and generalised convulsive seizures with electrographic features of encephalopathy with generalised and independent multifocal spike-wave discharges (PMID 31754459), another case had brain, immune, bone and intestinal dysfunction (PMID 27904971) and the third had metabolic dysfunction mimicking biotinidase deficiency (PMID 31392107). This condition could be treated with biotin supplementation and introduction of pantothenic acid supplementation (PMID 31392107).
Sources: Literature
Likely inborn error of metabolism - targeted testing not possible v2.8 QRSL1 Eleanor Williams Phenotypes for gene: QRSL1 were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis) to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 40, 618835
Likely inborn error of metabolism - targeted testing not possible v2.4 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
Likely inborn error of metabolism - targeted testing not possible v2.4 Sarah Leigh Panel version has been signed off
Likely inborn error of metabolism - targeted testing not possible v2.1 PCYT2 Sarah Leigh edited their review of gene: PCYT2: Added comment: Vaz et al. (2019 - PMID: 31637422 - DDD study among the co-authors) report on 5 individuals - from 4 families - with biallelic PCYT2 mutations. The phenotype corresponded to a complex hererditary paraplegia with global DD, regression (4/5), ID (mild in 3/5, severe in 2/5), spastic para-/tetraparesis, epilepsy (5/5 - variable onset 2-16 yrs - focal or tonic-clonic seizures) and progressive cerebral and cerebellar atrophy. Exome sequencing in all revealed biallelic PCYT2 variants, confirmed with Sanger s. in probands and their parents (NM_001184917.2 - corresponding to the canonical transcript used as Ref below): - P1 (Fam1) : 2 missense SNVs in trans configuration, c.730C>T or p.His244Tyr and c.920C>T or p.Pro307Leu - P2 (Fam2 - consanguineous of White British origin), P3 (Fam3 - Consanguineous of Turkish origin), P4,5 (Fam4 - consanguineous, unspecified origin) : homozygosity for c.1129C>T or p.Arg377Ter) affecting the last exon of 8/12 transcripts, including the canonical one. Individuals with the same genotype displayed variable degrees of ID (eg P3 - severe / P2, P4,5 - mild ID). For sibs in Fam4, homozygosity for a missense SACS variant led to consideration of the respective disorder (AR spastic ataxia of Charlevoix-Saguenay) though the variant was predicted to be tolerated in silico and notably the MRI images not suggestive. All variants were absent from / had extremely low AF in public databases, with no homozygotes. Posphatidylethanolamine (PE) is a membrane lipid, particularly enriched in human brain (45% of phospholypid fraction). PE is synthesized either via the CDP-ethanolamine pathway or by decarboxylation of phosphatidylserine in mitochondria. PCYT2 encodes CTP:phosophoethanolamine cytidyltransferase (ET) which is an ubiquitously expressed rate-limiting enzyme for PE biosynthesis in the former pathway. In silico, the 2 missense variants - localizing in the CTP catalytic domain 2 - were predicted to be damaging, as well as to affect protein stability. Fibroblasts of 3 patients (P1, P2, P3) representing all variants were studied: - Enzymatic activity was shown to be significantly reduced (though not absent) compared to controls. Abnormalities were noted upon Western Blot incl. absence in all 3 patients studied of one of the 2 bands normally found in controls (probably representing the longer isoform), reduced intensity in all 3 of another band probably corresponding to a shorter isoform, and presence of an additional band of intermediate molec. mass in patients with the truncating variant. - RT-PCR on mRNA from patient fibroblasts did not reveal (significant) reduction compared to controls. - Lipidomic profile of patient fibroblasts was compatible with the location of the block in the phospholipid biosynthesis pathway and different from controls. The lipidomic profile had similarities with what has been reported for EPT1 deficiency, the enzyme directly downstream of ET. The SELENO1-related phenotype (/EPT1 deficiency) is also highly overlapping. CRISPR-Cas9 was used to generate pcyt2 partial or complete knockout (ko) zebrafish, targeting either the final (ex13) or another exon (ex3) respectively. mRNA expression was shown to be moderately reduced in the first case and severely reduced/absent in the second, compared to wt. Similarly, complete-ko (ex3) led to significantly lower survival, with impaired though somewhat better survival of partial-ko (ex13) zebrafish. Complete knockout of Pcyt2 in mice is embryonically lethal (PMID cited: 17325045) while heterozygous mice develop features of metabolic syndrome (PMID cited: 22764088). Given lethality in knockout zebrafish / mice and the residual activity (15-20%) in patient fibroblasts, the variants reported were thought to be hypomorphic and complete loss of function possibly incompatible with life. PCYT2 is not associated with any phenotype in OMIM/G2P/SysID and not commonly included in gene panels for ID. As a result this gene could included in the ID / epilepsy panels with green (~/>3 indiv/fam/variants with the nonsense found in different populations, consistent phenotype, lipidomics, in silico/in vitro/in vivo evidence) or amber rating. [Please consider inclusion in other possibly relevant panels eg. for metabolic disorders, etc]. Sources: Literature
Konstantinos Varvagiannis (Other), 11 Nov 2019; Changed rating: GREEN
Likely inborn error of metabolism - targeted testing not possible v2.1 PCYT2 Sarah Leigh gene: PCYT2 was added
gene: PCYT2 was added to Inborn errors of metabolism. Sources: Literature
Mode of inheritance for gene: PCYT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCYT2 were set to 31637422; 17325045; 22764088
Phenotypes for gene: PCYT2 were set to Global developmental delay; Developmental regression; Intellectual disability; Spastic paraparesis; Seizures; Spastic tetraparesis; Cerebral atrophy; Cerebellar atrophy
Review for gene: PCYT2 was set to RED
Added comment: This gene was added by an external reviewer and rated Green on Hereditary spastic paraplegia gene panel (Version 1.210), and confirmed with Zerin Hyder (Genomics England Clinical Team) that this is appropriate to be Green on the Inborn errors of metabolism panel. The rating of this gene will be changed when the next reiteration of this panel is made.
Sources: Literature
Likely inborn error of metabolism - targeted testing not possible v2.0 Sarah Leigh promoted panel to version 2.0
Likely inborn error of metabolism - targeted testing not possible v1.426 Sarah Leigh Panel types changed to GMS Rare Disease Virtual; Component Of Super Panel; GMS signed-off
Likely inborn error of metabolism - targeted testing not possible v1.425 PDK3 Sarah Leigh changed review comment from: 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.; 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.
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.
The phenotype of ?Charcot-Marie-Tooth disease, X-linked dominant, 6 300905, is not relevant to the "Inborn errors of metabolism" panel, which is why it is rated Amber (clinical opinion of Helen Britain, GEL Clinical Fellow).
Likely inborn error of metabolism - targeted testing not possible v1.422 UPB1 Ellen McDonagh changed review comment from: Additional comments were provided by Dr Clare Beesley and colleagues (Great Ormond Street Hospital for Children NHS Foundation Trust) as part of the GMS Metabolic Specialist disease test group: 16 mutations reported in HGMD & several families have been reported in the literature. Heterologous expression of A85E mutant enzyme in E. coli yielded no residual activity (Van Kuilenburg et al., 2004, PMID: 15385443].; to: Additional comments were provided by Dr Clare Beesley and colleagues (Great Ormond Street Hospital for Children NHS Foundation Trust) as part of the GMS Metabolic Specialist disease test group: 16 mutations reported in HGMD & several families have been reported in the literature. Heterologous expression of A85E mutant enzyme in E. coli yielded no residual activity (Van Kuilenburg et al., 2004, PMID: 15385443).
Likely inborn error of metabolism - targeted testing not possible v1.422 UPB1 Ellen McDonagh commented on gene: UPB1: Additional comments were provided by Dr Clare Beesley and colleagues (Great Ormond Street Hospital for Children NHS Foundation Trust) as part of the GMS Metabolic Specialist disease test group: 16 mutations reported in HGMD & several families have been reported in the literature. Heterologous expression of A85E mutant enzyme in E. coli yielded no residual activity (Van Kuilenburg et al., 2004, PMID: 15385443].
Likely inborn error of metabolism - targeted testing not possible v1.422 TMEM199 Ellen McDonagh Classified gene: TMEM199 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.422 TMEM199 Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to feedback from the GMS Metabolic Specialist disease test group: 4 patients from 3 unrelated families reported in the literature. All patients had a type 2 pattern on serum transferrin isoelectric focusing (IEF), indicating abnormal N-glycosylation, as well as abnormal IEF of ApoC-III, indicating abnormal O-glycosylation (PMID:26833330).
Likely inborn error of metabolism - targeted testing not possible v1.422 TMEM199 Ellen McDonagh Gene: tmem199 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.421 ALG2 Ellen McDonagh Classified gene: ALG2 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.421 ALG2 Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Amber due to feedback from the GMS Metabolic Specialist disease test group. Information provided: 1 patient described with functional studies carried out: Expression of wildtype but not of mutant ALG2 cDNA restored the mannosyltransferase activity and the biosynthesis of dolichol-linked oligosaccharides both in patient fibroblasts and in yeast cells with an ALG2 mutation (PMID: 12684507).
Likely inborn error of metabolism - targeted testing not possible v1.421 ALG2 Ellen McDonagh Gene: alg2 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.420 BCAT2 Ellen McDonagh Classified gene: BCAT2 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.420 BCAT2 Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to expert review from representation of the GMS Metabolic disease specialist test group; multiple cases reported and this is a treatable.
Likely inborn error of metabolism - targeted testing not possible v1.420 BCAT2 Ellen McDonagh Gene: bcat2 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.417 UPB1 Ellen McDonagh Classified gene: UPB1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.417 UPB1 Ellen McDonagh Added comment: Comment on list classification: Based on new review by metabolic disease specialist on behalf of the GMS metabolic specialist tets group, and additional publications, this gene has been promoted from Red to Green.
Likely inborn error of metabolism - targeted testing not possible v1.417 UPB1 Ellen McDonagh Gene: upb1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.414 GLS Ellen McDonagh Phenotypes for gene: GLS were changed from Glucosidase 1 deficiency (Disorders of protein N-glycosylation) to Glucosidase 1 deficiency (Disorders of protein N-glycosylation); Epileptic encephalopathy, early infantile, 71 618328; Global developmental delay, progressive ataxia, and elevated glutamine 618412
Likely inborn error of metabolism - targeted testing not possible v1.413 GLS Ellen McDonagh Classified gene: GLS as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.413 GLS Ellen McDonagh Added comment: Comment on list classification: Due to expert review, evidence of 2 unrelated families for loss-of-function variants and further evidence for the role of this gene with an STR reported, this gene has been promoted from Red to Green.
Likely inborn error of metabolism - targeted testing not possible v1.413 GLS Ellen McDonagh Gene: gls has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.406 SLC25A32 Catherine Snow gene: SLC25A32 was added
gene: SLC25A32 was added to Inborn errors of metabolism. Sources: Expert Review Green,Expert list
Mode of inheritance for gene: SLC25A32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A32 were set to 26933868; 28443623
Phenotypes for gene: SLC25A32 were set to ?Exercise intolerance, riboflavin-responsive
Likely inborn error of metabolism - targeted testing not possible v1.406 PET117 Catherine Snow gene: PET117 was added
gene: PET117 was added to Inborn errors of metabolism. Sources: Expert Review Amber,Expert list
Mode of inheritance for gene: PET117 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PET117 were set to 28386624
Phenotypes for gene: PET117 were set to lesions in the medulla oblongata
Likely inborn error of metabolism - targeted testing not possible v1.405 COASY Catherine Snow Classified gene: COASY as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.405 COASY Catherine Snow Gene: coasy has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.405 COASY Catherine Snow Classified gene: COASY as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.405 COASY Catherine Snow Gene: coasy has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.405 COASY Catherine Snow Classified gene: COASY as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.405 COASY Catherine Snow Gene: coasy has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.404 COASY Catherine Snow gene: COASY was added
gene: COASY was added to Inborn errors of metabolism. Sources: Expert list
Mode of inheritance for gene: COASY was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COASY were set to 30089828
Phenotypes for gene: COASY were set to Neurodegeneration with brain iron accumulation 6, 615643; Pontocerebellar hypoplasia, type 12, 618266
Review for gene: COASY was set to AMBER
Added comment: COASY has sufficient evidence to be made Green however as it has been purposefully not rated by experts as Green on Mitochondrial Panels COASY will be rated as Amber.
Sources: Expert list
Likely inborn error of metabolism - targeted testing not possible v1.401 MRPS7 Catherine Snow Classified gene: MRPS7 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.401 MRPS7 Catherine Snow Gene: mrps7 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.401 MRPS7 Catherine Snow Classified gene: MRPS7 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.401 MRPS7 Catherine Snow Gene: mrps7 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.400 UQCC3 Catherine Snow changed review comment from: Comment on list classification: Promoting to Amber as some evidence is avaliable; to: Comment on list classification: Promoting to Amber as some evidence is available
Likely inborn error of metabolism - targeted testing not possible v1.399 UQCC3 Catherine Snow Classified gene: UQCC3 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.399 UQCC3 Catherine Snow Gene: uqcc3 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.399 UQCC3 Catherine Snow Classified gene: UQCC3 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.399 UQCC3 Catherine Snow Added comment: Comment on list classification: Promoting to Amber as some evidence is avaliable
Likely inborn error of metabolism - targeted testing not possible v1.399 UQCC3 Catherine Snow Gene: uqcc3 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.398 UQCC2 Catherine Snow Classified gene: UQCC2 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.398 UQCC2 Catherine Snow Added comment: Comment on list classification: This gene was promoted from Amber to Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter. Two unrelated cases reported, with functional supporting evidence.
Likely inborn error of metabolism - targeted testing not possible v1.398 UQCC2 Catherine Snow Gene: uqcc2 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.397 UQCC2 Catherine Snow Classified gene: UQCC2 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.397 UQCC2 Catherine Snow Added comment: Comment on list classification: This gene was promoted from Amber to Green due to the overall review and evidence assessment from the GMS mitochondrial specialist test group, submitted by Carl Fratter. Two unrelated cases reported, with functional supporting evidence.
Likely inborn error of metabolism - targeted testing not possible v1.397 UQCC2 Catherine Snow Gene: uqcc2 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.396 SLC25A4 Catherine Snow Added comment: Comment on mode of inheritance: The MOI was changed for consistency between panels Mitochondrial DNA maintenance disorder (code: 533) and Possible mitochondrial disorder - nuclear genes (code: 539).
Likely inborn error of metabolism - targeted testing not possible v1.395 ABCB7 Catherine Snow Added comment: Comment on mode of inheritance: Changed MOI for consistency amongst other panels. XLR in OMIM.
Likely inborn error of metabolism - targeted testing not possible v1.395 ABCB7 Catherine Snow Added comment: Comment on mode of inheritance: Changed MOI for consistency amongst other panels. XLR in OMIM.
Likely inborn error of metabolism - targeted testing not possible v1.393 Ellen McDonagh List of related panels changed from Likely inborn error of metabolism - targeted testing not possible to Likely inborn error of metabolism - targeted testing not possible; Likely inborn error of metabolism; R98
Likely inborn error of metabolism - targeted testing not possible v1.391 SETX Catherine Snow Classified gene: SETX as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.391 SETX Catherine Snow Gene: setx has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.390 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
Likely inborn error of metabolism - targeted testing not possible v1.390 SKIV2L Catherine Snow Classified gene: SKIV2L as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.390 SKIV2L Catherine Snow Gene: skiv2l has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.389 SLC12A3 Catherine Snow Classified gene: SLC12A3 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.389 SLC12A3 Catherine Snow Gene: slc12a3 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.388 SLC12A3 Catherine Snow Classified gene: SLC12A3 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.388 SLC12A3 Catherine Snow Gene: slc12a3 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.387 SLC18A2 Catherine Snow Classified gene: SLC18A2 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.387 SLC18A2 Catherine Snow Gene: slc18a2 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.387 SLC18A2 Catherine Snow Classified gene: SLC18A2 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.387 SLC18A2 Catherine Snow Gene: slc18a2 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.386 SLC35A2 Catherine Snow Classified gene: SLC35A2 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.386 SLC35A2 Catherine Snow Gene: slc35a2 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.386 SLC35A2 Catherine Snow Classified gene: SLC35A2 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.386 SLC35A2 Catherine Snow Gene: slc35a2 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.385 SLC3A1 Catherine Snow Classified gene: SLC3A1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.385 SLC3A1 Catherine Snow Gene: slc3a1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.384 SLC6A3 Catherine Snow Classified gene: SLC6A3 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.384 SLC6A3 Catherine Snow Gene: slc6a3 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.383 SDHC Ivone Leong changed review comment from: his 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 is present as an Amber gene on the Mitochondrial disorder with complex II deficiency (v 1.0) and Possible mitochondrial disorder - nuclear genes (v 1.12). Both GMS panels have been signed off by the GMS Metabolic Consensus Specialist Test Group. Therefore, this gene will remain Amber until further evidence is available.; 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.

This gene is present as an Amber gene on the Mitochondrial disorder with complex II deficiency (v 1.0) and Possible mitochondrial disorder - nuclear genes (v 1.12). Both GMS panels have been signed off by the GMS Metabolic Consensus Specialist Test Group. Therefore, this gene will remain Amber until further evidence is available.
Likely inborn error of metabolism - targeted testing not possible v1.383 RBP4 Ivone Leong Classified gene: RBP4 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.383 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.
Likely inborn error of metabolism - targeted testing not possible v1.383 RBP4 Ivone Leong Gene: rbp4 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.382 SLC6A8 Catherine Snow changed review comment from: 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.

Comment on list classification: Promoted from Amber to Green. SLC6A8 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.; 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.
Promoted from Amber to Green. SLC6A8 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.
Likely inborn error of metabolism - targeted testing not possible v1.382 SLC6A8 Catherine Snow Classified gene: SLC6A8 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.382 SLC6A8 Catherine Snow Gene: slc6a8 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.381 SLC7A9 Catherine Snow Classified gene: SLC7A9 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.381 SLC7A9 Catherine Snow Gene: slc7a9 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.379 UQCRC2 Catherine Snow Classified gene: UQCRC2 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.379 UQCRC2 Catherine Snow Added comment: Comment on list classification: Promoted from Red to Amber due to two unrelated cases/families - though this is for the same missense variant.
Likely inborn error of metabolism - targeted testing not possible v1.379 UQCRC2 Catherine Snow Gene: uqcrc2 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.375 NNT Catherine Snow Classified gene: NNT as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.375 NNT Catherine Snow Gene: nnt has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.374 TRAP1 Catherine Snow Classified gene: TRAP1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.374 TRAP1 Catherine Snow Gene: trap1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.374 TRAP1 Catherine Snow Classified gene: TRAP1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.374 TRAP1 Catherine Snow Gene: trap1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.372 LYRM4 Catherine Snow Classified gene: LYRM4 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.372 LYRM4 Catherine Snow Gene: lyrm4 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.372 LYRM4 Catherine Snow Classified gene: LYRM4 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.372 LYRM4 Catherine Snow Gene: lyrm4 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.367 LARS Catherine Snow Classified gene: LARS as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.367 LARS Catherine Snow Gene: lars has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.366 TTC37 Catherine Snow Classified gene: TTC37 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.366 TTC37 Catherine Snow Gene: ttc37 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.363 ST3GAL3 Catherine Snow Classified gene: ST3GAL3 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.363 ST3GAL3 Catherine Snow Gene: st3gal3 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.362 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
Likely inborn error of metabolism - targeted testing not possible v1.362 TREX1 Catherine Snow edited their review of gene: TREX1: Changed phenotypes: Aicardi-Goutieres syndrome 1, dominant and recessive, 225750
Likely inborn error of metabolism - targeted testing not possible v1.361 WFS1 Catherine Snow Classified gene: WFS1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.361 WFS1 Catherine Snow Gene: wfs1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.360 VKORC1 Catherine Snow Classified gene: VKORC1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.360 VKORC1 Catherine Snow Gene: vkorc1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.359 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
Likely inborn error of metabolism - targeted testing not possible v1.358 VIPAS39 Catherine Snow Classified gene: VIPAS39 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.358 VIPAS39 Catherine Snow Gene: vipas39 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.357 VIPAS39 Catherine Snow reviewed gene: VIPAS39: Rating: GREEN; Mode of pathogenicity: None; Publications: 22753090, 26808426; Phenotypes: Arthrogryposis, renal dysfunction, and cholestasis 2, 613404; Mode of inheritance: None
Likely inborn error of metabolism - targeted testing not possible v1.357 VPS33B Catherine Snow Classified gene: VPS33B as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.357 VPS33B Catherine Snow Gene: vps33b has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.356 VPS33B Catherine Snow Classified gene: VPS33B as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.356 VPS33B Catherine Snow Gene: vps33b has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.356 VPS33B Catherine Snow Classified gene: VPS33B as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.356 VPS33B Catherine Snow Gene: vps33b has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.355 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
Likely inborn error of metabolism - targeted testing not possible v1.354 UMOD Catherine Snow Classified gene: UMOD as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.354 UMOD Catherine Snow Gene: umod has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.353 TTPA Catherine Snow Classified gene: TTPA as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.353 TTPA Catherine Snow Gene: ttpa has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.353 TTPA Catherine Snow Classified gene: TTPA as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.353 TTPA Catherine Snow Gene: ttpa has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.353 TTPA Catherine Snow Classified gene: TTPA as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.353 TTPA Catherine Snow Gene: ttpa has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.352 TTPA Catherine Snow Classified gene: TTPA as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.352 TTPA Catherine Snow Gene: ttpa has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.351 TREX1 Catherine Snow Added comment: Comment on phenotypes: Aicardi-Goutieres syndrome 1, dominant and recessive TREX1 deficiency leads to the intracellular accumulation of DNA, and activation of the immune system by these accumulated NA.
Likely inborn error of metabolism - targeted testing not possible v1.350 TREX1 Catherine Snow Classified gene: TREX1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.350 TREX1 Catherine Snow 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
Likely inborn error of metabolism - targeted testing not possible v1.350 TREX1 Catherine Snow Gene: trex1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.347 TH Catherine Snow Classified gene: TH as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.347 TH Catherine Snow Gene: th has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.346 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
Likely inborn error of metabolism - targeted testing not possible v1.346 TCN2 Catherine Snow Classified gene: TCN2 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.346 TCN2 Catherine Snow Gene: tcn2 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.343 TAT Catherine Snow Classified gene: TAT as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.343 TAT Catherine Snow Gene: tat has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.340 STS Catherine Snow Classified gene: STS as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.340 STS Catherine Snow Gene: sts has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.339 STS Catherine Snow reviewed gene: STS: Rating: GREEN; Mode of pathogenicity: None; Publications: 1539590, 29672931; Phenotypes: Ichthyosis, X-linked, 308100; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Likely inborn error of metabolism - targeted testing not possible v1.339 ISCA2 Sarah Leigh Classified gene: ISCA2 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.339 ISCA2 Sarah Leigh Gene: isca2 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.336 ISCA2 Sarah Leigh Classified gene: ISCA2 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.336 ISCA2 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 different ethinicities.
Rated green based on review of Anna de Burca (Clinical Fellow, Genomic England).
Likely inborn error of metabolism - targeted testing not possible v1.336 ISCA2 Sarah Leigh Gene: isca2 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.331 SLC2A1 Ivone Leong Classified gene: SLC2A1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.331 SLC2A1 Ivone Leong 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.

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.
Likely inborn error of metabolism - targeted testing not possible v1.331 SLC2A1 Ivone Leong Gene: slc2a1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.330 HSPA9 Sarah Leigh Added comment: Comment on phenotypes: EVEN-PLUS syndrome of congenital malformations and skeletal dysplasia;Epiphyseal, Vertebral, Ear, Nose, plus associated findings.
Monoallelic variants reported in Anemia, sideroblastic, 4 182170.
Likely inborn error of metabolism - targeted testing not possible v1.330 HSPA9 Sarah Leigh Phenotypes for gene: HSPA9 were changed from EVEN-PLUS syndrome of congenital malformations and skeletal dysplasia; Epiphyseal, Vertebral, Ear, Nose, plus associated findings to Even-plus syndrome 616854
Likely inborn error of metabolism - targeted testing not possible v1.329 HSPA9 Sarah Leigh Classified gene: HSPA9 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.329 HSPA9 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 cases.
Likely inborn error of metabolism - targeted testing not possible v1.329 HSPA9 Sarah Leigh Gene: hspa9 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.328 FDX2 Sarah Leigh Classified gene: FDX2 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.328 FDX2 Sarah Leigh Added comment: Comment on list classification: Based on reviews from Carl Fratter and Zornitza Stark.
Likely inborn error of metabolism - targeted testing not possible v1.328 FDX2 Sarah Leigh Gene: fdx2 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.327 FDX2 Sarah Leigh Phenotypes for gene: FDX2 were changed from No OMIM phenotype?Mitochondrial myopathy with lactic acidosis, association with, 255125 to Mitochondrial myopathy, episodic, with optic atrophy and reversible leukoencephalopathy 251900
Likely inborn error of metabolism - targeted testing not possible v1.323 COX8A 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 1 variant reported in a 12.5-year old girl, born of Turkish parents who were likely distantly related, with mitochondrial complex I deficiency.
No further variants reported to date (30/09/2019).; to: Comment on list classification: 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).
Likely inborn error of metabolism - targeted testing not possible v1.323 COX8A Sarah Leigh Classified gene: COX8A as Red List (low evidence)
Likely inborn error of metabolism - targeted testing not possible v1.323 COX8A 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 in a 12.5-year old girl, born of Turkish parents who were likely distantly related, with mitochondrial complex I deficiency.
No further variants reported to date (30/09/2019).
Likely inborn error of metabolism - targeted testing not possible v1.323 COX8A Sarah Leigh Gene: cox8a has been classified as Red List (Low Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.321 COQ7 Sarah Leigh Classified gene: COQ7 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.321 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.
Likely inborn error of metabolism - targeted testing not possible v1.321 COQ7 Sarah Leigh Gene: coq7 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.318 MT-CO3 Louise Daugherty Phenotypes for gene: MT-CO3 were changed from to LEBER OPTIC ATROPHY; SEIZURES AND LACTIC ACIDOSIS; MITOCHONDRIAL COMPLEX IV DEFICIENCY
Likely inborn error of metabolism - targeted testing not possible v1.317 MT-CO3 Louise Daugherty Publications for gene: MT-CO3 were set to LEBER OPTIC ATROPHY; SEIZURES AND LACTIC ACIDOSIS; MITOCHONDRIAL COMPLEX IV DEFICIENCY
Likely inborn error of metabolism - targeted testing not possible v1.315 TMEM126A Sarah Leigh Classified gene: TMEM126A as Red List (low evidence)
Likely inborn error of metabolism - targeted testing not possible v1.315 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
Likely inborn error of metabolism - targeted testing not possible v1.315 TMEM126A Sarah Leigh Gene: tmem126a has been classified as Red List (Low Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.313 PDK3 Sarah Leigh Classified gene: PDK3 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.313 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.
Likely inborn error of metabolism - targeted testing not possible v1.313 PDK3 Sarah Leigh Gene: pdk3 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.311 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.
Likely inborn error of metabolism - targeted testing not possible v1.311 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.
Likely inborn error of metabolism - targeted testing not possible v1.311 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.
Likely inborn error of metabolism - targeted testing not possible v1.311 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).
Likely inborn error of metabolism - targeted testing not possible v1.311 COA5 Sarah Leigh changed review comment from: 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. No additional variants have been reported to date.; 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. Associated with phenotype in OMIM and as a possible G2P. At least 1 variant reported.
Likely inborn error of metabolism - targeted testing not possible v1.311 COA5 Sarah Leigh changed review comment from: Comment on list classification: No additional variants have been reported to date.; 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. No additional variants have been reported to date.
Likely inborn error of metabolism - targeted testing not possible v1.311 ATP5E Sarah Leigh changed review comment from: Comment on list classification: Based on 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. Based on Amber review collated by Carl Fratter May 2019 on behalf of GMS mitochondrial specialist test group: 1 reported case with functional studies.
Likely inborn error of metabolism - targeted testing not possible v1.311 ATP5A1 Sarah Leigh changed review comment from: Comment on list classification: 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: 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 mentioned in this article have inherited a heterozygous variant from their father while not expressing the maternal allele due to unknown variant affecting expression.
Likely inborn error of metabolism - targeted testing not possible v1.308 PDK1 Sarah Leigh Classified gene: PDK1 as Red List (low evidence)
Likely inborn error of metabolism - targeted testing not possible v1.308 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.
Likely inborn error of metabolism - targeted testing not possible v1.308 PDK1 Sarah Leigh Gene: pdk1 has been classified as Red List (Low Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.305 NDUFA12 Sarah Leigh Classified gene: NDUFA12 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.305 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.
Likely inborn error of metabolism - targeted testing not possible v1.305 NDUFA12 Sarah Leigh Gene: ndufa12 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.305 NDUFA12 Sarah Leigh Classified gene: NDUFA12 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.305 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.
Likely inborn error of metabolism - targeted testing not possible v1.305 NDUFA12 Sarah Leigh Gene: ndufa12 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.304 MRPS16 Sarah Leigh Classified gene: MRPS16 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.304 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.
Likely inborn error of metabolism - targeted testing not possible v1.304 MRPS16 Sarah Leigh Gene: mrps16 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.303 MRPS16 Sarah Leigh Added comment: Comment on phenotypes: Multiple respiratory chain complex deficiencies (disorders of protein synthesis);Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only));CORPUS CALLOSUM, AGENESIS OF, WITH DYSMORPHISM AND FATAL LACTIC ACIDOSIS
Likely inborn error of metabolism - targeted testing not possible v1.303 MRPS16 Sarah Leigh Phenotypes for gene: MRPS16 were changed from Combined oxidative phosphorylation deficiency 2, 610498; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); CORPUS CALLOSUM, AGENESIS OF, WITH DYSMORPHISM AND FATAL LACTIC ACIDOSIS to Combined oxidative phosphorylation deficiency 2 610498
Likely inborn error of metabolism - targeted testing not possible v1.301 COX4I2 Sarah Leigh Phenotypes for gene: COX4I2 were changed from Exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis, 612714; Mitochondrial Diseases; 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
Likely inborn error of metabolism - targeted testing not possible v1.299 COX4I2 Sarah Leigh Classified gene: COX4I2 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.299 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).
Likely inborn error of metabolism - targeted testing not possible v1.299 COX4I2 Sarah Leigh Gene: cox4i2 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.289 ATP5E Sarah Leigh Classified gene: ATP5E as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.289 ATP5E Sarah Leigh Added comment: Comment on list classification: Based on Amber review collated by Carl Fratter May 2019 on behalf of GMS mitochondrial specialist test group: 1 reported case with functional studies.
Likely inborn error of metabolism - targeted testing not possible v1.289 ATP5E Sarah Leigh Gene: atp5e has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.287 STAT2 Sarah Leigh Classified gene: STAT2 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.287 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.
Likely inborn error of metabolism - targeted testing not possible v1.287 STAT2 Sarah Leigh Gene: stat2 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.286 SPTLC1 Catherine Snow changed review comment from: Promoted from Amber to Green. This gene is associated with a relevant disease in OMIM and there is enough evidence to support a gene-disease association.

SPTLC1, encodes one of the two subunits of serine palmitoyltransferase (SPT), the enzyme catalyzing the first and rate-limiting step in the de novo synthesis of sphingolipids. PMID 20097765 reports that mutations in SPTLC1 cause a gain of function mechanism, which results in the formation of two atypical and neurotoxic sphingolipid metabolites.

Confirmed cases in Bristol (see review on Hereditary Neuropathy panel https://panelapp.genomicsengland.co.uk/panels/85/) and in sufficient publications.; to: Promoted from Amber to Green. This gene is associated with a relevant disease in OMIM and there is enough evidence to support a gene-disease association.

SPTLC1, encodes one of the two subunits of serine palmitoyltransferase (SPT), the enzyme catalyzing the first and rate-limiting step in the de novo synthesis of sphingolipids. PMID 20097765 reports that mutations in SPTLC1 cause a gain of function mechanism, which results in the formation of two atypical and neurotoxic sphingolipid metabolites.

Confirmed cases in Bristol (see review on Hereditary Neuropathy panel https://panelapp.genomicsengland.co.uk/panels/85/) and in sufficient publications.

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.
Likely inborn error of metabolism - targeted testing not possible v1.286 SPTLC1 Catherine Snow Classified gene: SPTLC1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.286 SPTLC1 Catherine Snow Gene: sptlc1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.283 SPTLC2 Catherine Snow Classified gene: SPTLC2 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.283 SPTLC2 Catherine Snow Gene: sptlc2 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.281 SPTLC2 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.
SPTLC2, encodes one of the two subunits of serine palmitoyltransferase (SPT), the enzyme catalyzing the first and rate-limiting step in the de novo synthesis of sphingolipids. PMID: 20920666 reports on three heterozygous missense mutations in the SPTLC2 subunit of SPT in four families and also confirmed cases in Bristol (see review on Hereditary Neuropathy panel https://panelapp.genomicsengland.co.uk/panels/85/).
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: 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.

SPTLC2, encodes one of the two subunits of serine palmitoyltransferase (SPT), the enzyme catalyzing the first and rate-limiting step in the de novo synthesis of sphingolipids. PMID: 20920666 reports on three heterozygous missense mutations in the SPTLC2 subunit of SPT in four families and also confirmed cases in Bristol (see review on Hereditary Neuropathy panel https://panelapp.genomicsengland.co.uk/panels/85/).

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.
Likely inborn error of metabolism - targeted testing not possible v1.280 SPR Catherine Snow Classified gene: SPR as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.280 SPR Catherine Snow Gene: spr has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.279 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
Likely inborn error of metabolism - targeted testing not possible v1.279 DNM2 Sarah Leigh Classified gene: DNM2 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.279 DNM2 Sarah Leigh Gene: dnm2 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.279 DNM2 Sarah Leigh Classified gene: DNM2 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.279 DNM2 Sarah Leigh Gene: dnm2 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.278 IER3IP1 Sarah Leigh changed review comment from: Comment on list classification: IER3IP1 has been demoted to Red on the Mitochondrial disorders panel on the recommendation of the GMS mitochondrial specialist test group, including by Carl Fratter (Oxford University Hospitals NHS Trust). It is associated with Microcephaly, epilepsy, and diabetes syndrome 614231, which is not technically a mitochondrial disorder, as the phenotype is quite different to other mitochondrial conditions, thus in the opinion of Helen Britain the phenotypes reported, the condition could initially present as a mimic of a mitochondrial presentation e.g. abnormal liver enzymes, diabetes, neurological dysfunction and therefore a green rating on metabolic panels would seem appropriate.; to: Comment on list classification: IER3IP1 has been demoted to Red on the Mitochondrial disorders panel on the recommendation of the GMS mitochondrial specialist test group, including by Carl Fratter (Oxford University Hospitals NHS Trust). It is associated with Microcephaly, epilepsy, and diabetes syndrome 614231, which is not technically a mitochondrial disorder, as the phenotype is quite different to other mitochondrial conditions. Thus in the opinion of Helen Britain (Genomics England Clinical Fellow) the phenotypes reported could initially present as a mimic of a mitochondrial presentation e.g. abnormal liver enzymes, diabetes, neurological dysfunction and therefore a green rating on metabolic panels would seem appropriate.
Likely inborn error of metabolism - targeted testing not possible v1.278 IER3IP1 Sarah Leigh changed review comment from: Comment on list classification: IER3IP1 is being demoted to Red on this panel on the recommendation of the GMS mitochondrial specialist test group, including by Carl Fratter (Oxford University Hospitals NHS Trust). As it is associated with Microcephaly, epilepsy, and diabetes syndrome 614231, which is not technically a mitochondrial disorder, as the phenotype is quite different to other mitochondrial conditions.; to: Comment on list classification: IER3IP1 has been demoted to Red on the Mitochondrial disorders panel on the recommendation of the GMS mitochondrial specialist test group, including by Carl Fratter (Oxford University Hospitals NHS Trust). It is associated with Microcephaly, epilepsy, and diabetes syndrome 614231, which is not technically a mitochondrial disorder, as the phenotype is quite different to other mitochondrial conditions, thus in the opinion of Helen Britain the phenotypes reported, the condition could initially present as a mimic of a mitochondrial presentation e.g. abnormal liver enzymes, diabetes, neurological dysfunction and therefore a green rating on metabolic panels would seem appropriate.
Likely inborn error of metabolism - targeted testing not possible v1.278 SLC2A1 Ivone Leong Phenotypes for gene: SLC2A1 were changed from Intellectual disability; Early onset dystonia; Cataracts; Glucose transporter 1 deficiency (blood-brain barrier) (Disorders of glucose transport); Hereditary ataxia; Epileptic encephalopathy; Familial Genetic Generalised Epilepsies to Intellectual disability; Early onset dystonia; Cataracts; Glucose transporter 1 deficiency (blood-brain barrier) (Disorders of glucose transport); Hereditary ataxia; Epileptic encephalopathy; Familial Genetic Generalised Epilepsies; GLUT1 deficiency syndrome 1, infantile onset, severe, 606777; GLUT1 deficiency syndrome 2, childhood onset, 612126
Likely inborn error of metabolism - targeted testing not possible v1.277 SDHAF2 Ivone Leong edited their review of gene: SDHAF2: Added comment: 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 is present as an Amber gene on the Mitochondrial disorder with complex II deficiency (v 1.0) and Possible mitochondrial disorder - nuclear genes (v 1.12). Both GMS panels have been signed off by the GMS Metabolic Consensus Specialist Test Group. Therefore, this gene will remain Amber until further evidence is available.; Changed rating: AMBER
Likely inborn error of metabolism - targeted testing not possible v1.277 SC5D Ivone Leong Classified gene: SC5D as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.277 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.

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.
Likely inborn error of metabolism - targeted testing not possible v1.277 SC5D Ivone Leong Gene: sc5d has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.275 SC5D Ivone Leong Phenotypes for gene: SC5D were changed from Lathosterolosis (Disorders of sterol biosynthesis); Intellectual disability; Cataracts to Lathosterolosis, 607330; Intellectual disability; Cataracts
Likely inborn error of metabolism - targeted testing not possible v1.274 RNASEH2C Ivone Leong Classified gene: RNASEH2C as Red List (low evidence)
Likely inborn error of metabolism - targeted testing not possible v1.274 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.

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.
Likely inborn error of metabolism - targeted testing not possible v1.274 RNASEH2C Ivone Leong Gene: rnaseh2c has been classified as Red List (Low Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.273 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.

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: 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.

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.
Likely inborn error of metabolism - targeted testing not possible v1.273 RNASEH2B Ivone Leong Classified gene: RNASEH2B as Red List (low evidence)
Likely inborn error of metabolism - targeted testing not possible v1.273 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.

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.
Likely inborn error of metabolism - targeted testing not possible v1.273 RNASEH2B Ivone Leong Gene: rnaseh2b has been classified as Red List (Low Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.272 RNASEH2A Ivone Leong Classified gene: RNASEH2A as Red List (low evidence)
Likely inborn error of metabolism - targeted testing not possible v1.272 RNASEH2A Ivone Leong Gene: rnaseh2a has been classified as Red List (Low Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.271 COA6 Sarah Leigh Classified gene: COA6 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.271 COA6 Sarah Leigh Gene: coa6 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.270 PEX5 Sarah Leigh Added comment: Comment on phenotypes: Peroxisome biogenesis disorder 2A (Zellweger) 214110;Peroxisome biogenesis disorder 2B 202370;Rhizomelic chondrodysplasia punctata, type 5 616716
Likely inborn error of metabolism - targeted testing not possible v1.270 PEX5 Sarah Leigh Phenotypes for gene: PEX5 were changed from Disorders of peroxisome biogenesis; Peroxisome biogenesis disorder 2A (Zellweger) to Disorders of peroxisome biogenesis; Peroxisome biogenesis disorder 2A (Zellweger)
Likely inborn error of metabolism - targeted testing not possible v1.269 PEX5 Sarah Leigh Gene: pex5 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.269 GTPBP3 Sarah Leigh Added comment: Comment on phenotypes: Mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis and encephalopathy;Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
Likely inborn error of metabolism - targeted testing not possible v1.269 GTPBP3 Sarah Leigh Phenotypes for gene: GTPBP3 were changed from Combined oxidative phosphorylation deficiency 23; mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis and encephalopathy; Multiple respiratory chain complex deficiencies (disorders of protein synthesis) to Combined oxidative phosphorylation deficiency 23 616198
Likely inborn error of metabolism - targeted testing not possible v1.268 GTPBP3 Sarah Leigh Gene: gtpbp3 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.268 DPM2 Sarah Leigh Gene: dpm2 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.266 CYP7B1 Sarah Leigh changed review comment from: 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 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.; 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.
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 3 unrelated cases of Bile acid synthesis defect, congenital, 3 613812, which is a more relevant phenotype for metabolic panels.
Likely inborn error of metabolism - targeted testing not possible v1.266 CYP7B1 Sarah Leigh Classified gene: CYP7B1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.266 CYP7B1 Sarah Leigh Gene: cyp7b1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.266 CYP7B1 Sarah Leigh Classified gene: CYP7B1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.266 CYP7B1 Sarah Leigh Gene: cyp7b1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.265 CYP7B1 Sarah Leigh changed review comment from: Comment on list classification: Although there is enough evidence for an association with Spastic paraplegia 5A, autosomal recessive 270800, only one variant has been reported in Bile acid synthesis defect, congenital, 3 613812, which is the more relevant phenotype for metabolic panels.; to: Comment on list classification: Although there is enough evidence for an association with Spastic paraplegia 5A, autosomal recessive 270800, only one variant has been reported in 3 unrelated cases of Bile acid synthesis defect, congenital, 3 613812, which is the more relevant phenotype for metabolic panels.
Likely inborn error of metabolism - targeted testing not possible v1.265 CYP7B1 Sarah Leigh Classified gene: CYP7B1 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.265 CYP7B1 Sarah Leigh Added comment: Comment on list classification: Although there is enough evidence for an association with Spastic paraplegia 5A, autosomal recessive 270800, only one variant has been reported in Bile acid synthesis defect, congenital, 3 613812, which is the more relevant phenotype for metabolic panels.
Likely inborn error of metabolism - targeted testing not possible v1.265 CYP7B1 Sarah Leigh Gene: cyp7b1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.264 PTS Ivone Leong Classified gene: PTS as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.264 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.
Likely inborn error of metabolism - targeted testing not possible v1.264 PTS Ivone Leong Gene: pts has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.262 ALAS2 Sarah Leigh Classified gene: ALAS2 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.262 ALAS2 Sarah Leigh Gene: alas2 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.261 ADSL Sarah Leigh Classified gene: ADSL as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.261 ADSL Sarah Leigh Gene: adsl has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.260 ABHD12 Sarah Leigh Classified gene: ABHD12 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.260 ABHD12 Sarah Leigh Gene: abhd12 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.259 ADA Sarah Leigh Classified gene: ADA as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.259 ADA Sarah Leigh Gene: ada has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.259 ACY1 Sarah Leigh Classified gene: ACY1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.259 ACY1 Sarah Leigh Gene: acy1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.258 ABHD12 Sarah Leigh Classified gene: ABHD12 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.258 ABHD12 Sarah Leigh Gene: abhd12 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.258 ABCG8 Sarah Leigh Classified gene: ABCG8 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.258 ABCG8 Sarah Leigh Gene: abcg8 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.257 ABCG5 Sarah Leigh Classified gene: ABCG5 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.257 ABCG5 Sarah Leigh Gene: abcg5 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.256 ALDH3A2 Sarah Leigh Classified gene: ALDH3A2 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.256 ALDH3A2 Sarah Leigh Gene: aldh3a2 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.255 ALAS2 Sarah Leigh commented on gene: ALAS2: 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 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.
Likely inborn error of metabolism - targeted testing not possible v1.255 ADA Sarah Leigh commented on gene: ADA: 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 30 variants reported associated with Adenosine deaminase deficiency.
Likely inborn error of metabolism - targeted testing not possible v1.254 ALAS2 Sarah Leigh edited their review of gene: ALAS2: Added comment: 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 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 mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Likely inborn error of metabolism - targeted testing not possible v1.254 ADA Sarah Leigh reviewed gene: ADA: Rating: GREEN; Mode of pathogenicity: ; Publications: 27604308, 3684597, 2783588, 1680289; 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; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism - targeted testing not possible v1.254 ABHD12 Sarah Leigh reviewed gene: ABHD12: Rating: GREEN; Mode of pathogenicity: ; Publications: 27604308, 20797687, 24697911 ; 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); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism - targeted testing not possible v1.254 ABCG8 Sarah Leigh reviewed gene: ABCG8: Rating: GREEN; Mode of pathogenicity: ; Publications: 27604308, 11452359, 15996216, 11099417, 22981120; Phenotypes: Sitosterolemia 210250, Familial hypercholesterolaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism - targeted testing not possible v1.254 ABCG5 Sarah Leigh reviewed gene: ABCG5: Rating: GREEN; Mode of pathogenicity: ; Publications: 27604308, 11099417, 11138003, 20719861, 17976197; Phenotypes: Sitosterolemia 210250, Familial hypercholesterolaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism - targeted testing not possible v1.253 PSPH Sarah Leigh Phenotypes for gene: PSPH were changed from Intellectual disability; Phosphoserine phosphatase deficiency (Disorders of serine, glycine or glycerate metabolism); Unexplained skeletal dysplasia to Phosphoserine phosphatase deficiency 614023
Likely inborn error of metabolism - targeted testing not possible v1.252 PSAT1 Sarah Leigh Classified gene: PSAT1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.252 PSAT1 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 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.
Likely inborn error of metabolism - targeted testing not possible v1.252 PSAT1 Sarah Leigh Gene: psat1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.250 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
Likely inborn error of metabolism - targeted testing not possible v1.249 PRPS1 Sarah Leigh Phenotypes for gene: PRPS1 were changed from Intellectual disability; Charcot-Marie-Tooth disease; Phosphoribosyl pyrophosphate synthetase 1 defects (Disorders of purine metabolism); Congenital hearing impairment (profound/severe); 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
Likely inborn error of metabolism - targeted testing not possible v1.248 PRPS1 Sarah Leigh Classified gene: PRPS1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.248 PRPS1 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 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.
Likely inborn error of metabolism - targeted testing not possible v1.248 PRPS1 Sarah Leigh Gene: prps1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.246 GATC Sarah Leigh Classified gene: GATC as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.246 GATC Sarah Leigh Added comment: Comment on list classification: This rating is based on the evidence that GATB, GATC & QRSL1 are functioning together in the development of this condition.
Likely inborn error of metabolism - targeted testing not possible v1.246 GATC Sarah Leigh Gene: gatc has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.245 GATC Sarah Leigh Classified gene: GATC as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.245 GATC Sarah Leigh Added comment: Comment on list classification: This rating is based on the evidence that GATB, GATC & QRSL1 are functioning together in the development of this condition.
Likely inborn error of metabolism - targeted testing not possible v1.245 GATC Sarah Leigh Gene: gatc has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.245 GATC Sarah Leigh Classified gene: GATC as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.245 GATC Sarah Leigh Added comment: Comment on list classification: This rating is based on the evidence that GATB, GATC & QRSL1 are functioning together in the development of this condition.
Likely inborn error of metabolism - targeted testing not possible v1.245 GATC Sarah Leigh Gene: gatc has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.243 ATP5A1 Sarah Leigh Classified gene: ATP5A1 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.243 ATP5A1 Sarah Leigh Added comment: Comment on list classification: 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.
Likely inborn error of metabolism - targeted testing not possible v1.243 ATP5A1 Sarah Leigh Gene: atp5a1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.241 POR Sarah Leigh Classified gene: POR as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.241 POR 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 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.
Likely inborn error of metabolism - targeted testing not possible v1.241 POR Sarah Leigh Gene: por has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.240 PITRM1 Sarah Leigh Classified gene: PITRM1 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.240 PITRM1 Sarah Leigh Added comment: Comment on list classification: This gene is being demoted to amber as it has not been reviewed as green by the GMS Mitochondrial specialist test group.
Likely inborn error of metabolism - targeted testing not possible v1.240 PITRM1 Sarah Leigh Gene: pitrm1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.239 POR Sarah Leigh Phenotypes for gene: POR were changed from Antley-Bixler syndrome with disordered steroidogenesis; Unexplained skeletal dysplasia; Disorders of sex development; Craniosynostosis syndromes phenotypes to Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis 201750; Disordered steroidogenesis due to cytochrome P450 oxidoreductase 613571
Likely inborn error of metabolism - targeted testing not possible v1.237 PNP Sarah Leigh Classified gene: PNP as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.237 PNP 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 10 variants reported.
Likely inborn error of metabolism - targeted testing not possible v1.237 PNP Sarah Leigh Gene: pnp has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.237 PNP Sarah Leigh Classified gene: PNP as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.237 PNP 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 10 variants reported.
Likely inborn error of metabolism - targeted testing not possible v1.237 PNP Sarah Leigh Gene: pnp has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.236 PNP Sarah Leigh Added comment: Comment on phenotypes: SCID;Purine nucleoside phosphorylase deficiency (Disorders of purine metabolism)
Likely inborn error of metabolism - targeted testing not possible v1.236 PNP Sarah Leigh Phenotypes for gene: PNP were changed from SCID; Purine nucleoside phosphorylase deficiency (Disorders of purine metabolism) to Immunodeficiency due to purine nucleoside phosphorylase deficiency 613179
Likely inborn error of metabolism - targeted testing not possible v1.235 PINK1 Sarah Leigh Classified gene: PINK1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.235 PINK1 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 12 variants were reported.
Likely inborn error of metabolism - targeted testing not possible v1.235 PINK1 Sarah Leigh Gene: pink1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.232 PIGM Sarah Leigh Classified gene: PIGM as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.232 PIGM 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 possible Gen2Phen gene. At least 1 variant was reported in 2 unrelated families (PMID 16767100), together with supportive functional studies (PMID 17442906 & 25293775).
Likely inborn error of metabolism - targeted testing not possible v1.232 PIGM Sarah Leigh Gene: pigm has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.231 PIGM Sarah Leigh Classified gene: PIGM as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.231 PIGM 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 possible Gen2Phen gene. At least 1 variant was reported in 2 unrelated families (PMID 16767100), together with supportive functional studies (PMID 17442906 & 25293775).
Likely inborn error of metabolism - targeted testing not possible v1.231 PIGM Sarah Leigh Gene: pigm has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.231 PIGM Sarah Leigh Classified gene: PIGM as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.231 PIGM 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 possible Gen2Phen gene. At least 1 variant was reported in 2 unrelated families (PMID 16767100), together with supportive functional studies (PMID 17442906 & 25293775).
Likely inborn error of metabolism - targeted testing not possible v1.231 PIGM Sarah Leigh Gene: pigm has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.228 PIGM Sarah Leigh Added comment: Comment on phenotypes: Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation;Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency
Likely inborn error of metabolism - targeted testing not possible v1.228 PIGM Sarah Leigh Phenotypes for gene: PIGM were changed from Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation; Glycosylphosphatidylinositol deficiency, 610293; Glycosylphosphatidylinositol deficiency 610293; Phosphatidylinositolglycan, class M deficiency (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation); Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency to Glycosylphosphatidylinositol deficiency 610293
Likely inborn error of metabolism - targeted testing not possible v1.226 PHGDH Sarah Leigh Classified gene: PHGDH as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.226 PHGDH 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 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.
Likely inborn error of metabolism - targeted testing not possible v1.226 PHGDH Sarah Leigh Gene: phgdh has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.225 PHGDH Sarah Leigh Phenotypes for gene: PHGDH were changed from Phosphoglycerate dehydrogenase deficiency (Disorders of serine, glycine or glycerate metabolism); Unexplained skeletal dysplasia; Intellectual disability to Neu-Laxova syndrome 1 256520; Phosphoglycerate dehydrogenase deficiency 601815
Likely inborn error of metabolism - targeted testing not possible v1.222 PEPD Sarah Leigh Classified gene: PEPD as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.222 PEPD 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 11 variants reported.
Likely inborn error of metabolism - targeted testing not possible v1.222 PEPD Sarah Leigh Gene: pepd has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.222 PEPD Sarah Leigh Classified gene: PEPD as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.222 PEPD 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 11 variants reported.
Likely inborn error of metabolism - targeted testing not possible v1.222 PEPD Sarah Leigh Gene: pepd has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.220 PDPR Sarah Leigh changed review comment from: 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 1 variant reported in a case of global developmental delay, typical Joubert syndrome, according to PMID 25558065.; 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 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.
Likely inborn error of metabolism - targeted testing not possible v1.219 PDPR Sarah Leigh Classified gene: PDPR as Red List (low evidence)
Likely inborn error of metabolism - targeted testing not possible v1.219 PDPR 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 1 variant reported in a case of global developmental delay, typical Joubert syndrome, according to PMID 25558065.
Likely inborn error of metabolism - targeted testing not possible v1.219 PDPR Sarah Leigh Gene: pdpr has been classified as Red List (Low Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.215 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.
Likely inborn error of metabolism - targeted testing not possible v1.214 PCSK9 Sarah Leigh Classified gene: PCSK9 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.214 PCSK9 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 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.
Likely inborn error of metabolism - targeted testing not possible v1.214 PCSK9 Sarah Leigh Gene: pcsk9 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.214 PCSK9 Sarah Leigh Phenotypes for gene: PCSK9 were changed from Hypercholesterolemia, familial, 3 603776; {Low density lipoprotein cholesterol level QTL 1} 60377 to Hypercholesterolemia, familial, 3 603776; {Low density lipoprotein cholesterol level QTL 1} 603776
Likely inborn error of metabolism - targeted testing not possible v1.212 PCSK9 Sarah Leigh Phenotypes for gene: PCSK9 were changed from Familial hypercholesterolaemia; Autosomal dominant hypercholesterolemia-3 (Inherited hypercholesterolaemias) to Hypercholesterolemia, familial, 3 603776; {Low density lipoprotein cholesterol level QTL 1} 60377
Likely inborn error of metabolism - targeted testing not possible v1.211 PCK1 Sarah Leigh Classified gene: PCK1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.211 PCK1 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 unrelated cases.
Likely inborn error of metabolism - targeted testing not possible v1.211 PCK1 Sarah Leigh Gene: pck1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.210 PCK1 Sarah Leigh Classified gene: PCK1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.210 PCK1 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 unrelated cases.
Likely inborn error of metabolism - targeted testing not possible v1.210 PCK1 Sarah Leigh Gene: pck1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.210 PCK1 Sarah Leigh Classified gene: PCK1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.210 PCK1 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 unrelated cases.
Likely inborn error of metabolism - targeted testing not possible v1.210 PCK1 Sarah Leigh Gene: pck1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.207 PCK1 Sarah Leigh Added comment: Comment on phenotypes: Phosphoenolpyruvate carboxykinase deficiency (Disorders of gluconeogenesis);Cytosolic phosphoenolpyruvate carboxykinase (PEPCK))
Likely inborn error of metabolism - targeted testing not possible v1.207 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
Likely inborn error of metabolism - targeted testing not possible v1.205 PANK2 Sarah Leigh Classified gene: PANK2 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.205 PANK2 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 13 variants reported for Neurodegeneration with brain iron accumulation 234200 and 3 variants in 2 unrelated cases of HARP syndrome 607236.
Likely inborn error of metabolism - targeted testing not possible v1.205 PANK2 Sarah Leigh Gene: pank2 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.205 PANK2 Sarah Leigh Classified gene: PANK2 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.205 PANK2 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 13 variants reported for Neurodegeneration with brain iron accumulation 234200 and 3 variants in 2 unrelated cases of HARP syndrome 607236.
Likely inborn error of metabolism - targeted testing not possible v1.205 PANK2 Sarah Leigh Gene: pank2 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.202 OPLAH Sarah Leigh Classified gene: OPLAH as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.202 OPLAH 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 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.
Likely inborn error of metabolism - targeted testing not possible v1.202 OPLAH Sarah Leigh Gene: oplah has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.200 OCRL Sarah Leigh Classified gene: OCRL as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.200 OCRL 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 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.
Likely inborn error of metabolism - targeted testing not possible v1.200 OCRL Sarah Leigh Gene: ocrl has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.200 OCRL Sarah Leigh Classified gene: OCRL as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.200 OCRL 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 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.
Likely inborn error of metabolism - targeted testing not possible v1.200 OCRL Sarah Leigh Gene: ocrl has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.199 OCRL Sarah Leigh Added comment: Comment on phenotypes: Lowe syndrome (Disorders of amino acid transport);Renal tract calcification (or Nephrolithiasis/nephrocalcinosis);Intellectual disability;Intellectual_disability;Cataracts
Likely inborn error of metabolism - targeted testing not possible v1.199 OCRL Sarah Leigh Added comment: Comment on phenotypes: Lowe syndrome (Disorders of amino acid transport);Renal tract calcification (or Nephrolithiasis/nephrocalcinosis);Intellectual disability;Intellectual_disability;Cataracts
Likely inborn error of metabolism - targeted testing not possible v1.199 OCRL Sarah Leigh Phenotypes for gene: OCRL were changed from Lowe syndrome (Disorders of amino acid transport); Renal tract calcification (or Nephrolithiasis/nephrocalcinosis); Intellectual disability; Intellectual_disability; Cataracts to Dent disease 2 300555; Lowe syndrome 309000
Likely inborn error of metabolism - targeted testing not possible v1.198 OCRL Sarah Leigh Phenotypes for gene: OCRL were changed from Lowe syndrome (Disorders of amino acid transport); Renal tract calcification (or Nephrolithiasis/nephrocalcinosis); Intellectual disability; Intellectual_disability; Cataracts to Lowe syndrome (Disorders of amino acid transport); Renal tract calcification (or Nephrolithiasis/nephrocalcinosis); Intellectual disability; Intellectual_disability; Cataracts
Likely inborn error of metabolism - targeted testing not possible v1.196 OCRL Sarah Leigh Phenotypes for gene: OCRL were changed from Lowe syndrome (Disorders of amino acid transport); Renal tract calcification (or Nephrolithiasis/nephrocalcinosis); Intellectual disability; Intellectual_disability; Cataracts to Lowe syndrome (Disorders of amino acid transport); Renal tract calcification (or Nephrolithiasis/nephrocalcinosis); Intellectual disability; Intellectual_disability; Cataracts
Likely inborn error of metabolism - targeted testing not possible v1.195 NDUFB9 Sarah Leigh Classified gene: NDUFB9 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.195 NDUFB9 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 1 variant reported, together with supportive functional studies.
Likely inborn error of metabolism - targeted testing not possible v1.195 NDUFB9 Sarah Leigh Gene: ndufb9 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.190 MVK Sarah Leigh Classified gene: MVK as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.190 MVK 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 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.
Likely inborn error of metabolism - targeted testing not possible v1.190 MVK Sarah Leigh Gene: mvk has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.189 MVK Sarah Leigh Added comment: Comment on phenotypes: Infantile enterocolitis & monogenic inflammatory bowel disease;Mevalonate kinase deficiency (Disorders of sterol biosynthesis)
Likely inborn error of metabolism - targeted testing not possible v1.189 MVK Sarah Leigh Phenotypes for gene: MVK were changed from Infantile enterocolitis & monogenic inflammatory bowel disease; Mevalonate kinase deficiency (Disorders of sterol biosynthesis) to Hyper-IgD syndrome 260920; Mevalonic aciduria 610377; Porokeratosis 3, multiple types 175900
Likely inborn error of metabolism - targeted testing not possible v1.188 MTPAP Sarah Leigh Added comment: Comment on phenotypes: Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)
Likely inborn error of metabolism - targeted testing not possible v1.188 MTPAP Sarah Leigh Phenotypes for gene: MTPAP were changed from ?Spastic ataxia 4, autosomal recessive 613672; Ataxia, spastic, 4, 613672; ?Spastic ataxia 4, autosomal recessive, 613672; Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only) to ?Spastic ataxia 4, autosomal recessive 613672
Likely inborn error of metabolism - targeted testing not possible v1.186 MTFMT Sarah Leigh Added comment: Comment on phenotypes: Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)).
Likely inborn error of metabolism - targeted testing not possible v1.186 MTFMT Sarah Leigh Phenotypes for gene: MTFMT were changed from Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Combined oxidative phosphorylation deficiency 15, 614947; Inherited white matter disorders; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Mitochondrial complex I deficiency, nuclear type 27 618248 to Combined oxidative phosphorylation deficiency 15 614947; Mitochondrial complex I deficiency, nuclear type 27 618248
Likely inborn error of metabolism - targeted testing not possible v1.185 MRPL3 Sarah Leigh Added comment: Comment on phenotypes: Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only))
Likely inborn error of metabolism - targeted testing not possible v1.185 MRPL3 Sarah Leigh Phenotypes for gene: MRPL3 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 9, 614582 to Combined oxidative phosphorylation deficiency 9 614582
Likely inborn error of metabolism - targeted testing not possible v1.184 MOCS2 Sarah Leigh Classified gene: MOCS2 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.184 MOCS2 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 9 variants reported in at least 8 unrelated cases, together with supportive functional studies.
Likely inborn error of metabolism - targeted testing not possible v1.184 MOCS2 Sarah Leigh Gene: mocs2 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.180 MOCS1 Sarah Leigh Classified gene: MOCS1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.180 MOCS1 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 5 variants reported unrelated cases.
Likely inborn error of metabolism - targeted testing not possible v1.180 MOCS1 Sarah Leigh Gene: mocs1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.176 MAOA Sarah Leigh Classified gene: MAOA as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.176 MAOA 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 4 variants reported in unrelated cases.
Likely inborn error of metabolism - targeted testing not possible v1.176 MAOA Sarah Leigh Gene: maoa has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.176 MAOA Sarah Leigh Classified gene: MAOA as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.176 MAOA 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 4 variants reported in unrelated cases.
Likely inborn error of metabolism - targeted testing not possible v1.176 MAOA Sarah Leigh Gene: maoa has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.175 MAGT1 Sarah Leigh Classified gene: MAGT1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.175 MAGT1 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 possible Gen2Phen gene. At least 3 variants reported in unrelated cases, together with mouse knock-out model (PMID 29581357).
Likely inborn error of metabolism - targeted testing not possible v1.175 MAGT1 Sarah Leigh Gene: magt1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.171 MAGT1 Sarah Leigh Phenotypes for gene: MAGT1 were changed from Combined B and T cell defect; Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia 300853; IAP-CDG (Disorders of protein N-glycosylation) to Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia 300853
Likely inborn error of metabolism - targeted testing not possible v1.170 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
Likely inborn error of metabolism - targeted testing not possible v1.169 LIPC Sarah Leigh Classified gene: LIPC as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.169 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.
Likely inborn error of metabolism - targeted testing not possible v1.169 LIPC Sarah Leigh Gene: lipc has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.168 LIPC Sarah Leigh Phenotypes for gene: LIPC were changed from {Diabetes mellitus, noninsulin-dependent} 125853; Hepatic lipase deficiency (Inherited mixed hyperlipidaemias); Hepatic lipase deficiency, 614025; [High density lipoprotein cholesterol level QTL 12] 612797 to {Diabetes mellitus, noninsulin-dependent} 125853; Hepatic lipase deficiency 614025; [High density lipoprotein cholesterol level QTL 12] 612797
Likely inborn error of metabolism - targeted testing not possible v1.167 LDLRAP1 Sarah Leigh Classified gene: LDLRAP1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.167 LDLRAP1 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 11 variants reported.
Likely inborn error of metabolism - targeted testing not possible v1.167 LDLRAP1 Sarah Leigh Gene: ldlrap1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.165 LDLRAP1 Sarah Leigh Added comment: Comment on phenotypes: Familial hypercholesterolaemia;Autosomal recessive hypercholesterolemia (Inherited hypercholesterolaemias)
Likely inborn error of metabolism - targeted testing not possible v1.165 LDLRAP1 Sarah Leigh Phenotypes for gene: LDLRAP1 were changed from Familial hypercholesterolaemia; Autosomal recessive hypercholesterolemia (Inherited hypercholesterolaemias) to Hypercholesterolemia, familial, 4 603813
Likely inborn error of metabolism - targeted testing not possible v1.162 LDLR Sarah Leigh Classified gene: LDLR as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.162 LDLR 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. Over 2000 variants reported.
Likely inborn error of metabolism - targeted testing not possible v1.162 LDLR Sarah Leigh Gene: ldlr has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.161 LDLR Sarah Leigh Added comment: Comment on phenotypes: Familial hypercholesterolaemia;Disorder of low density lipoprotein receptor (Inherited hypercholesterolaemias)
Likely inborn error of metabolism - targeted testing not possible v1.161 LDLR Sarah Leigh Phenotypes for gene: LDLR were changed from Familial hypercholesterolaemia; Disorder of low density lipoprotein receptor (Inherited hypercholesterolaemias) to Hypercholesterolemia, familial, 1 143890; LDL cholesterol level QTL2 143890
Likely inborn error of metabolism - targeted testing not possible v1.160 LBR Sarah Leigh Classified gene: LBR as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.160 LBR 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 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.
Likely inborn error of metabolism - targeted testing not possible v1.160 LBR Sarah Leigh Gene: lbr has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.158 LBR Sarah Leigh Added comment: Comment on phenotypes: Greenberg skeletal dysplasia (Disorders of sterol biosynthesis);Unexplained skeletal dysplasia;Fetal hydrops
Likely inborn error of metabolism - targeted testing not possible v1.158 LBR Sarah Leigh Phenotypes for gene: LBR were changed from Greenberg skeletal dysplasia (Disorders of sterol biosynthesis); Unexplained skeletal dysplasia; Fetal hydrops to ?Reynolds syndrome 613471; Greenberg skeletal dysplasia 215140; Pelger-Huet anomaly 169400; Pelger-Huet anomaly with mild skeletal anomalies 618019
Likely inborn error of metabolism - targeted testing not possible v1.156 HSD17B10 Sarah Leigh Classified gene: HSD17B10 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.156 HSD17B10 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 for 2-methyl-3-hydroxybutyrylL-coA dehydrogenase deficiency and for mental retardation syndromic X-linked type 10 . At least 8 variants reported.
Likely inborn error of metabolism - targeted testing not possible v1.156 HSD17B10 Sarah Leigh Gene: hsd17b10 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.151 HPS1 Sarah Leigh Classified gene: HPS1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.151 HPS1 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 7 variants reported in at least 5 unrelated cases.
Likely inborn error of metabolism - targeted testing not possible v1.151 HPS1 Sarah Leigh Gene: hps1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.149 HPD Sarah Leigh Classified gene: HPD as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.149 HPD 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 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).
Likely inborn error of metabolism - targeted testing not possible v1.149 HPD Sarah Leigh Gene: hpd has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.147 HPD Sarah Leigh Added comment: Comment on phenotypes: Intellectual disability;4-hydroxyphenylpyruvate dioxygenase deficiency (Disorders of phenylalanine or tyrosine metabolism)
Likely inborn error of metabolism - targeted testing not possible v1.147 HPD Sarah Leigh Phenotypes for gene: HPD were changed from Hawkinsinuria 140350; Tyrosinemia, type III 276710 to Hawkinsinuria 140350; Tyrosinemia, type III 276710
Likely inborn error of metabolism - targeted testing not possible v1.147 HPD Sarah Leigh Added comment: Comment on phenotypes: Intellectual disability;4-hydroxyphenylpyruvate dioxygenase deficiency (Disorders of phenylalanine or tyrosine metabolism)
Likely inborn error of metabolism - targeted testing not possible v1.147 HPD Sarah Leigh Phenotypes for gene: HPD were changed from Intellectual disability; 4-hydroxyphenylpyruvate dioxygenase deficiency (Disorders of phenylalanine or tyrosine metabolism) to Hawkinsinuria 140350; Tyrosinemia, type III 276710
Likely inborn error of metabolism - targeted testing not possible v1.146 HADH Sarah Leigh Classified gene: HADH as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.146 HADH 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. Numerous variants reported in unrelated cases of Hyperinsulinemic hypoglycemia, familial, 4 609975.
Likely inborn error of metabolism - targeted testing not possible v1.146 HADH Sarah Leigh Gene: hadh has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.143 GNMT Sarah Leigh Classified gene: GNMT as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.143 GNMT 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 2 unrelated cases, with supportive functional data.
Likely inborn error of metabolism - targeted testing not possible v1.143 GNMT Sarah Leigh Gene: gnmt has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.142 GNMT Sarah Leigh Classified gene: GNMT as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.142 GNMT 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 2 unrelated cases, with supportive functional data.
Likely inborn error of metabolism - targeted testing not possible v1.142 GNMT Sarah Leigh Gene: gnmt has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.142 GNMT Sarah Leigh Classified gene: GNMT as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.142 GNMT 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 2 unrelated cases, with supportive functional data.
Likely inborn error of metabolism - targeted testing not possible v1.142 GNMT Sarah Leigh Gene: gnmt has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.140 GLUL Sarah Leigh Classified gene: GLUL as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.140 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.
Likely inborn error of metabolism - targeted testing not possible v1.140 GLUL Sarah Leigh Gene: glul has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.135 GK Sarah Leigh Classified gene: GK as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.135 GK 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 8 variants reported.
Likely inborn error of metabolism - targeted testing not possible v1.135 GK Sarah Leigh Gene: gk has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.131 GAMT Sarah Leigh Classified gene: GAMT as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.131 GAMT 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 5 variants reported in 4 unrelated cases.
Likely inborn error of metabolism - targeted testing not possible v1.131 GAMT Sarah Leigh Gene: gamt has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.128 FTCD Sarah Leigh Classified gene: FTCD as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.128 FTCD 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 15 variants reported.
Likely inborn error of metabolism - targeted testing not possible v1.128 FTCD Sarah Leigh Gene: ftcd has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.124 FGFR2 Sarah Leigh Classified gene: FGFR2 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.124 FGFR2 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 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.
Likely inborn error of metabolism - targeted testing not possible v1.124 FGFR2 Sarah Leigh Gene: fgfr2 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.123 FGFR2 Sarah Leigh Phenotypes for gene: FGFR2 were changed from 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 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
Likely inborn error of metabolism - targeted testing not possible v1.122 FGFR2 Sarah Leigh Phenotypes for gene: FGFR2 were changed from 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 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
Likely inborn error of metabolism - targeted testing not possible v1.122 FGFR2 Sarah Leigh Phenotypes for gene: FGFR2 were changed from Bilateral microtia; Deafness and congenital structural abnormalities; Craniosynostosis syndromes phenotypes; Arthrogryposis; Choanal atresia; Antley-Bixler syndrome type without disordered steroidogenesis; 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
Likely inborn error of metabolism - targeted testing not possible v1.120 FECH Sarah Leigh Classified gene: FECH as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.120 FECH 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 phenotype in OMIM and not in Gen2Phen. At least 16 variants identified in unrelated cases.
Likely inborn error of metabolism - targeted testing not possible v1.120 FECH Sarah Leigh Gene: fech has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.119 FECH Sarah Leigh Phenotypes for gene: FECH were changed from Erythropoietic protoporphyria, mild variant; Erythropoietic protoporphyria (Porphyrias with acute painful photosensitivity) to Protoporphyria, erythropoietic, 1 177000
Likely inborn error of metabolism - targeted testing not possible v1.118 DPM3 Sarah Leigh Classified gene: DPM3 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.118 DPM3 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 probable Gen2Phen gene. At least 2 variants reported as homozygotes in two unrelated cases, together with segregation and supportive functional studies.
Likely inborn error of metabolism - targeted testing not possible v1.118 DPM3 Sarah Leigh Gene: dpm3 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.115 DHDDS Sarah Leigh Classified gene: DHDDS as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.115 DHDDS 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 probable Gen2Phen gene for Retinitis pigmentosa 59 613861. One variant was reported in at least 15 families with retinitis pigmentosa, but only one compound individual with glycosylation defects was identifed so far (PMID 27343064).
Likely inborn error of metabolism - targeted testing not possible v1.115 DHDDS Sarah Leigh Gene: dhdds has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.113 DHODH Sarah Leigh Classified gene: DHODH as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.113 DHODH 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 11 variants reported in 6 families (PMID 19915526), together with a knockout mouse model (PMID 27626380).
Likely inborn error of metabolism - targeted testing not possible v1.113 DHODH Sarah Leigh Gene: dhodh has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.111 DHODH Sarah Leigh Added comment: Comment on phenotypes: Unexplained skeletal dysplasia;Bilateral microtia;Deafness and congenital structural abnormalities;Dihydroorotate dehydrogenase deficiency (Disorders of pyrimidine metabolism)
Likely inborn error of metabolism - targeted testing not possible v1.111 DHODH Sarah Leigh Phenotypes for gene: DHODH were changed from Unexplained skeletal dysplasia; Bilateral microtia; Deafness and congenital structural abnormalities; Dihydroorotate dehydrogenase deficiency (Disorders of pyrimidine metabolism) to Miller syndrome 263750
Likely inborn error of metabolism - targeted testing not possible v1.109 DHCR24 Sarah Leigh Classified gene: DHCR24 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.109 DHCR24 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 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.
Likely inborn error of metabolism - targeted testing not possible v1.109 DHCR24 Sarah Leigh Gene: dhcr24 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.109 DHCR24 Sarah Leigh Classified gene: DHCR24 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.109 DHCR24 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 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.
Likely inborn error of metabolism - targeted testing not possible v1.109 DHCR24 Sarah Leigh Gene: dhcr24 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.107 DHCR24 Sarah Leigh Added comment: Comment on phenotypes: Desmosterolosis (Disorders of sterol biosynthesis);Unexplained skeletal dysplasia;Intellectual disability
Likely inborn error of metabolism - targeted testing not possible v1.107 DHCR24 Sarah Leigh Phenotypes for gene: DHCR24 were changed from Desmosterolosis (Disorders of sterol biosynthesis); Unexplained skeletal dysplasia; Intellectual disability to Desmosterolosis 602398
Likely inborn error of metabolism - targeted testing not possible v1.104 DCXR Sarah Leigh Classified gene: DCXR as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.104 DCXR 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 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.
Likely inborn error of metabolism - targeted testing not possible v1.104 DCXR Sarah Leigh Gene: dcxr has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.101 CYP7B1 Sarah Leigh changed review comment from: 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 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 also had Bile acid synthesis defect, congenital, 3 613812.; 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.
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.
Likely inborn error of metabolism - targeted testing not possible v1.100 CYP7B1 Sarah Leigh Classified gene: CYP7B1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.100 CYP7B1 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 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 also had Bile acid synthesis defect, congenital, 3 613812.
Likely inborn error of metabolism - targeted testing not possible v1.100 CYP7B1 Sarah Leigh Gene: cyp7b1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.99 CYP7B1 Sarah Leigh Phenotypes for gene: CYP7B1 were changed from Bile acid synthesis defect, congenital, 3 to Bile acid synthesis defect, congenital, 3 613812; Spastic paraplegia 5A, autosomal recessive 270800
Likely inborn error of metabolism - targeted testing not possible v1.98 CTSC Sarah Leigh Classified gene: CTSC as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.98 CTSC 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 phenotype in OMIM and not in Gen2Phen. At least 13 variants identified in unrelated cases of Papillon-Lefevre syndrome 245000.
Likely inborn error of metabolism - targeted testing not possible v1.98 CTSC Sarah Leigh Gene: ctsc has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.97 CTSC Sarah Leigh Added comment: Comment on phenotypes: Papillon-Lef vre syndrome (Other lysosomal disorders, Cathepsin-related disorders);Unexplained skeletal dysplasia
Likely inborn error of metabolism - targeted testing not possible v1.97 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
Likely inborn error of metabolism - targeted testing not possible v1.96 CSTB Sarah Leigh Phenotypes for gene: CSTB were changed from Intellectual disability; Myoclonic epilepsy of Unverricht and Lundborg (Other metabolic disorders) to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) 254800
Likely inborn error of metabolism - targeted testing not possible v1.95 CLDN19 Sarah Leigh Added comment: Comment on phenotypes: Hypomagnesaemia type 5, renal with ocular involvement (Disorder of magnesium metabolism);Renal tract calcification (or Nephrolithiasis/nephrocalcinosis)
Likely inborn error of metabolism - targeted testing not possible v1.95 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
Likely inborn error of metabolism - targeted testing not possible v1.93 CLDN19 Sarah Leigh Classified gene: CLDN19 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.93 CLDN19 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 5 variants reported in at least 6 unrelated cases.
Likely inborn error of metabolism - targeted testing not possible v1.93 CLDN19 Sarah Leigh Gene: cldn19 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.92 CLDN16 Sarah Leigh Classified gene: CLDN16 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.92 CLDN16 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 phenotype in OMIM and not in Gen2Phen. At least 19 variants identified in unrelated cases.
Likely inborn error of metabolism - targeted testing not possible v1.92 CLDN16 Sarah Leigh Gene: cldn16 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.91 CLDN16 Sarah Leigh Added comment: Comment on phenotypes: Renal tract calcification (or Nephrolithiasis/nephrocalcinosis);Hypomagnesaemia type 3, renal (Disorder of magnesium metabolism)
Likely inborn error of metabolism - targeted testing not possible v1.91 CLDN16 Sarah Leigh Phenotypes for gene: CLDN16 were changed from Renal tract calcification (or Nephrolithiasis/nephrocalcinosis); Hypomagnesaemia type 3, renal (Disorder of magnesium metabolism) to Hypomagnesemia 3, renal 248250
Likely inborn error of metabolism - targeted testing not possible v1.90 CISD2 Sarah Leigh Classified gene: CISD2 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.90 CISD2 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 both RD and IF Gen2Phen gene. At least 3 variants reported in unrelated cases, together with segration and functional studies.
Likely inborn error of metabolism - targeted testing not possible v1.90 CISD2 Sarah Leigh Gene: cisd2 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.87 ASAH1 Sarah Leigh changed review comment from: 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.; 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. 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.
Likely inborn error of metabolism - targeted testing not possible v1.87 APOB Sarah Leigh changed review comment from: Comment on list classification: 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.; 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.
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.
Likely inborn error of metabolism - targeted testing not possible v1.87 APOB Sarah Leigh Classified gene: APOB as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.87 APOB Sarah Leigh Added comment: Comment on list classification: 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.
Likely inborn error of metabolism - targeted testing not possible v1.87 APOB Sarah Leigh Gene: apob has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.85 ALPL Sarah Leigh changed review comment from: 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).; 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.
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).
Likely inborn error of metabolism - targeted testing not possible v1.85 ALG13 Sarah Leigh changed review comment from: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 2 variants reported, one of which (c.320A>G, p.N107S) is associated with Epileptic encephalopathy, early infantile, 36 300884 as a de novo variant in at least 6 unrelated cases, athough the conection with Congenital disorder of glycosylation, type Is 300884 is not clear from these cases. The second variant was reported in an infant who died at age 1 year. Transferrin isoelectric focusing showed abnormal N-glycosylation and was consistent with a diagnostic classification of congenital disorder of glycosylation type Is (CDG1S). Studies of patient-derived cells showed decreased enzyme activity, at about 17% of wildtype (PMID 22492991).; 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.
Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 2 variants reported, one of which (c.320A>G, p.N107S) is associated with Epileptic encephalopathy, early infantile, 36 300884 as a de novo variant in at least 6 unrelated cases, athough the conection with Congenital disorder of glycosylation, type Is 300884 is not clear from these cases. The second variant was reported in an infant who died at age 1 year. Transferrin isoelectric focusing showed abnormal N-glycosylation and was consistent with a diagnostic classification of congenital disorder of glycosylation type Is (CDG1S). Studies of patient-derived cells showed decreased enzyme activity, at about 17% of wildtype (PMID 22492991).
Likely inborn error of metabolism - targeted testing not possible v1.83 ALPL Sarah Leigh Classified gene: ALPL as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.83 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).
Likely inborn error of metabolism - targeted testing not possible v1.83 ALPL Sarah Leigh Gene: alpl has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.82 ALPL Sarah Leigh Phenotypes for gene: ALPL were changed from Unexplained skeletal dysplasia; Osteogenesis Imperfecta; Craniosynostosis syndromes phenotypes; Hypophosphatasia (Disorders of pyridoxine metabolism) to Hypophosphatasia, adult 146300; Hypophosphatasia, childhood 241510; Hypophosphatasia, infantile241500; Odontohypophosphatasia 146300
Likely inborn error of metabolism - targeted testing not possible v1.81 ALG13 Sarah Leigh Classified gene: ALG13 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.81 ALG13 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 2 variants reported, one of which (c.320A>G, p.N107S) is associated with Epileptic encephalopathy, early infantile, 36 300884 as a de novo variant in at least 6 unrelated cases, athough the conection with Congenital disorder of glycosylation, type Is 300884 is not clear from these cases. The second variant was reported in an infant who died at age 1 year. Transferrin isoelectric focusing showed abnormal N-glycosylation and was consistent with a diagnostic classification of congenital disorder of glycosylation type Is (CDG1S). Studies of patient-derived cells showed decreased enzyme activity, at about 17% of wildtype (PMID 22492991).
Likely inborn error of metabolism - targeted testing not possible v1.81 ALG13 Sarah Leigh Gene: alg13 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.78 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).
Likely inborn error of metabolism - targeted testing not possible v1.78 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).
Likely inborn error of metabolism - targeted testing not possible v1.76 WARS2 Sarah Leigh Source Expert Review Green was added to WARS2.
Mode of inheritance for gene WARS2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, 617710 for gene: WARS2
Publications for gene WARS2 were changed from to 28650581; 28905505; 28236339
Rating Changed from Red List (low evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.76 TOP3A Sarah Leigh gene: TOP3A was added
gene: TOP3A was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: TOP3A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOP3A were set to 29290614
Phenotypes for gene: TOP3A were set to ?Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 5, 618098
Likely inborn error of metabolism - targeted testing not possible v1.76 SLC25A42 Sarah Leigh Source Expert Review Green was added to SLC25A42.
Mode of inheritance for gene SLC25A42 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Metabolic crises, recurrent, with variable encephalomyopathic features and neurologic regression 618416; mitochondrial myopathy for gene: SLC25A42
Publications for gene SLC25A42 were changed from to 26541337; 29923093; 29327420
Rating Changed from Red List (low evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.76 QRSL1 Sarah Leigh Source Expert Review Green was added to QRSL1.
Mode of inheritance for gene QRSL1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Multiple respiratory chain complex deficiencies (disorders of protein synthesis) for gene: QRSL1
Publications for gene QRSL1 were changed from to 29440775; 26741492
Rating Changed from Red List (low evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.76 PNPLA8 Sarah Leigh Source Expert Review Green was added to PNPLA8.
Mode of inheritance for gene PNPLA8 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes ?Mitochondrial myopathy with lactic acidosis, 251950 for gene: PNPLA8
Publications for gene PNPLA8 were changed from to 25473036; 25512002; 29681094
Rating Changed from Red List (low evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.76 PITRM1 Sarah Leigh Source Expert Review Green was added to PITRM1.
Added phenotypes mental retardation, spinocerebellar ataxia, cognitive decline and psychosis for gene: PITRM1
Publications for gene PITRM1 were changed from PMID: 26697887 to 26697887; 29383861; 29764912
Rating Changed from Red List (low evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.76 PARS2 Sarah Leigh Source Expert Review Green was added to PARS2.
Added phenotypes Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Epileptic encephalopathy, early infantile, 75, 618437; Alpers syndrome for gene: PARS2
Publications for gene PARS2 were changed from PMID: 25629079 (single case) to 28077841; 25629079; 29410512; 29915213
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.76 NAXE Sarah Leigh Source Expert Review Green was added to NAXE.
Mode of inheritance for gene NAXE was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy 617186 for gene: NAXE
Publications for gene NAXE were changed from to 27616477; 27290639; 27122014
Rating Changed from Red List (low evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.76 MTPAP Sarah Leigh Source Expert Review Green was added to MTPAP.
Added phenotypes ?Spastic ataxia 4, autosomal recessive 613672 for gene: MTPAP
Publications for gene MTPAP were changed from 27604308 to 27959697; 26319014; 25008111; 20970105; 27391121
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.76 MTFMT Sarah Leigh Source Expert Review Green was added to MTFMT.
Added phenotypes Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 15, 614947; Mitochondrial complex I deficiency, nuclear type 27 618248 for gene: MTFMT
Publications for gene MTFMT were changed from 27604308 to 21907147; 27564080; 23499752; 24461907
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.76 MICU1 Sarah Leigh Source Expert Review Green was added to MICU1.
Mode of inheritance for gene MICU1 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Myopathy with extrapyramidal signs 615673 for gene: MICU1
Publications for gene MICU1 were changed from to 24336167; 29721912
Rating Changed from Red List (low evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.76 LYRM7 Sarah Leigh Source Expert Review Green was added to LYRM7.
Mode of inheritance for gene LYRM7 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Isolated complex III deficiency; severe encephalopathy, lactic acidosis and profound, isolated cIII deficiency in skeletal muscle; leukoencephalopathy and complex III deficiency; 615838; Mitochondrial complex III deficiency, nuclear type 8 for gene: LYRM7
Publications for gene LYRM7 were changed from to 27564080; 24014394; 28694194; 27151179; 26912632
Rating Changed from Red List (low evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.76 LIPT2 Sarah Leigh Source Expert Review Green was added to LIPT2.
Added phenotypes Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities, 617668 for gene: LIPT2
Publications for gene LIPT2 were changed from to 28803783; 28757203
Rating Changed from Red List (low evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.76 ISCU Sarah Leigh Source Expert Review Green was added to ISCU.
Mode of inheritance for gene ISCU was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Added phenotypes Myopathy with lactic acidosis, hereditary, 255125; Disorders of iron homeostasis for gene: ISCU
Publications for gene ISCU were changed from 27604308 to 18304497; 29079705; 18296749; 19567699; 20206689
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.76 HARS2 Sarah Leigh Source Expert Review Green was added to HARS2.
Added phenotypes Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Perrault syndrome 2, 614926 for gene: HARS2
Publications for gene HARS2 were changed from 27604308 to 27650058; 21464306
Rating Changed from Red List (low evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.76 GFM2 Sarah Leigh Source Expert Review Green was added to GFM2.
Mode of inheritance for gene GFM2 was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Early-onset neurological presentations of mitochondrial disease for gene: GFM2
Publications for gene GFM2 were changed from to 22700954; 26016410; 29075935
Rating Changed from Red List (low evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.76 CARS2 Sarah Leigh Source Expert Review Green was added to CARS2.
Added phenotypes Multiple respiratory chain complex deficiencies (disorders of protein synthesis); No OMIM phenotype; Combined oxidative phosphorylation deficiency 27 616672 for gene: CARS2
Publications for gene CARS2 were changed from to 25361775; 25787132; 30139652
Rating Changed from Red List (low evidence) to Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.75 STAT2 Sarah Leigh Classified gene: STAT2 as Red List (low evidence)
Likely inborn error of metabolism - targeted testing not possible v1.75 STAT2 Sarah Leigh Added comment: Comment on list classification: STAT2 is rated as Red on this panel on the recommendation of the GMS mitochondrial specialist test group, including by Carl Fratter (Oxford University Hospitals NHS Trust). Although it is associated with elongated mitochondria, the Immunodeficiency 44 616636 phenotype is not appropriate for this panel.
Likely inborn error of metabolism - targeted testing not possible v1.75 STAT2 Sarah Leigh Gene: stat2 has been classified as Red List (Low Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.73 ROBO3 Sarah Leigh Classified gene: ROBO3 as Red List (low evidence)
Likely inborn error of metabolism - targeted testing not possible v1.73 ROBO3 Sarah Leigh Added comment: Comment on list classification: ROBO3 is being demoted to Red on this panel on the recommendation of the GMS mitochondrial specialist test group, including by Carl Fratter (Oxford University Hospitals NHS Trust). As it is associated with Gaze palsy, familial horizontal, with progressive scoliosis, 1 607313, which is not appropriate for this panel.
Likely inborn error of metabolism - targeted testing not possible v1.73 ROBO3 Sarah Leigh Gene: robo3 has been classified as Red List (Low Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.72 FXN Sarah Leigh Classified gene: FXN as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.72 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.
Likely inborn error of metabolism - targeted testing not possible v1.72 FXN Sarah Leigh Gene: fxn has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.71 RANBP2 Sarah Leigh Classified gene: RANBP2 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.71 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.
Likely inborn error of metabolism - targeted testing not possible v1.71 RANBP2 Sarah Leigh Gene: ranbp2 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.70 PGAM2 Sarah Leigh Classified gene: PGAM2 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.70 PGAM2 Sarah Leigh Added comment: Comment on list classification: Associated with phenotype in OMIM and not in Gen2Phen. At least 4 variants identified in 3 unrelated cases.
Likely inborn error of metabolism - targeted testing not possible v1.70 PGAM2 Sarah Leigh Gene: pgam2 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.70 PGAM2 Sarah Leigh Classified gene: PGAM2 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.70 PGAM2 Sarah Leigh Added comment: Comment on list classification: Associated with phenotype in OMIM and not in Gen2Phen. At least 4 variants identified in 3 unrelated cases.
Likely inborn error of metabolism - targeted testing not possible v1.70 PGAM2 Sarah Leigh Gene: pgam2 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.68 PGAM2 Sarah Leigh Phenotypes for gene: PGAM2 were changed from Glycogen storage disease type X (Glycogen storage disorders); Rhabdomyolysis and metabolic muscle disorders to Glycogen storage disease X 261670
Likely inborn error of metabolism - targeted testing not possible v1.67 MANBA Sarah Leigh Phenotypes for gene: MANBA were changed from Mannosidosis, beta to Mannosidosis, beta 248510
Likely inborn error of metabolism - targeted testing not possible v1.66 MANBA Sarah Leigh Classified gene: MANBA as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.66 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.
Likely inborn error of metabolism - targeted testing not possible v1.66 MANBA Sarah Leigh Gene: manba has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.65 ASAH1 Sarah Leigh Phenotypes for gene: ASAH1 were changed from Spinal muscular atrophy with progressive myoclonic epilepsy 159950, Farber lipogranulomatosis 228000, Fetal hydrops, Intellectual disability to Spinal muscular atrophy with progressive myoclonic epilepsy 159950, Farber lipogranulomatosis 228000, Fetal hydrops, Intellectual disability
Likely inborn error of metabolism - targeted testing not possible v1.63 ASAH1 Sarah Leigh Phenotypes for gene: ASAH1 were changed from Spinal muscular atrophy with progressive myoclonic epilepsy 159950, Farber lipogranulomatosis 228000, Fetal hydrops, Intellectual disability to Spinal muscular atrophy with progressive myoclonic epilepsy 159950, Farber lipogranulomatosis 228000, Fetal hydrops, Intellectual disability
Likely inborn error of metabolism - targeted testing not possible v1.63 ASAH1 Sarah Leigh Phenotypes for gene: ASAH1 were changed from Farber disease (Sphingolipidoses); Intellectual disability; Fetal hydrops to Spinal muscular atrophy with progressive myoclonic epilepsy 159950, Farber lipogranulomatosis 228000, Fetal hydrops, Intellectual disability
Likely inborn error of metabolism - targeted testing not possible v1.62 ASAH1 Sarah Leigh Classified gene: ASAH1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.62 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.
Likely inborn error of metabolism - targeted testing not possible v1.62 ASAH1 Sarah Leigh Gene: asah1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.62 ASAH1 Sarah Leigh Classified gene: ASAH1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.62 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.
Likely inborn error of metabolism - targeted testing not possible v1.62 ASAH1 Sarah Leigh Gene: asah1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.61 DHCR7 Sarah Leigh changed review comment from: Comment on list classification: Associated with phenotype in OMIM and as confirmed Gen2Phen gene. At least 21 variants reported.; to: Comment on list classification: Associated with phenotype in OMIM and as confirmed Gen2Phen gene. At least 21 variants reported.

Although single gene testing has been commissioned for DHCR7, it is well established as an inherited metabolic disorder and ought to be included in the overall panel in case it has not been biochemically excluded initially
Saikat Santra (Birmingham Children's Hospital), 21 Dec 2018
Likely inborn error of metabolism - targeted testing not possible v1.61 DHCR7 Sarah Leigh Classified gene: DHCR7 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.61 DHCR7 Sarah Leigh Added comment: Comment on list classification: Associated with phenotype in OMIM and as confirmed Gen2Phen gene. At least 21 variants reported.
Likely inborn error of metabolism - targeted testing not possible v1.61 DHCR7 Sarah Leigh Gene: dhcr7 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.60 PARS2 Eleanor Williams Phenotypes for gene: PARS2 were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Epileptic encephalopathy, early infantile, 75, 618437Alpers syndrome. to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Epileptic encephalopathy, early infantile, 75, 618437Alpers syndrome.
Likely inborn error of metabolism - targeted testing not possible v1.60 PARS2 Eleanor Williams Phenotypes for gene: PARS2 were changed from Multiple respiratory chain complex deficiencies (disorders of protein synthesis); No OMIM phenotype; Alpers syndrome. to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Epileptic encephalopathy, early infantile, 75, 618437Alpers syndrome.
Likely inborn error of metabolism - targeted testing not possible v1.55 UQCRQ Sarah Leigh Classified gene: UQCRQ as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v1.55 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).
Likely inborn error of metabolism - targeted testing not possible v1.55 UQCRQ Sarah Leigh Gene: uqcrq has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.50 MRPL44 Ellen McDonagh Classified gene: MRPL44 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.50 MRPL44 Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green on the Mitochondrial disorders (Version 1.138) gene panel due to to reports in 3 unrelated cases/families, therefore promoting this gene in this panel to reflect this change in rating. See publications for evidence.
Likely inborn error of metabolism - targeted testing not possible v1.50 MRPL44 Ellen McDonagh Gene: mrpl44 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.49 SLC35A1 Rebecca Foulger Classified gene: SLC35A1 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v1.49 SLC35A1 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green following promotion of SLC35A1 to Green on the component panel 'Congenital disorders of glycosylation'.
Likely inborn error of metabolism - targeted testing not possible v1.49 SLC35A1 Rebecca Foulger Gene: slc35a1 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v1.47 SI Ivone Leong Source NHS GMS was added to SI.
Source London North GLH was added to SI.
Likely inborn error of metabolism - targeted testing not possible v1.46 RRM2B Rebecca Foulger Phenotypes for gene: RRM2B were changed from 5,613077Mitochondrial DNA depletion syndrome 8B (MNGIE type), 612075; Mitochondrial DNA Depletion Syndrome (recessive); Mitochondrial Ribonucelotide Reductase subunit 2 deficiency (Disorders of purine metabolism); Progressive external ophthalmoplegia with mitochondrial DNA deletions (autosomal dominant); Disorders of mitochondrial DNA maintenance and integrity; Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy), 612075 to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 5, 613077; Mitochondrial DNA depletion syndrome 8B (MNGIE type), 612075; Mitochondrial DNA Depletion Syndrome (recessive); Mitochondrial Ribonucelotide Reductase subunit 2 deficiency (Disorders of purine metabolism); Progressive external ophthalmoplegia with mitochondrial DNA deletions (autosomal dominant); Disorders of mitochondrial DNA maintenance and integrity; Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy), 612075
Likely inborn error of metabolism - targeted testing not possible v1.44 TWNK Rebecca Foulger Phenotypes for gene: TWNK were changed from Mitochondrial Membrane Protein-Associated Neurodegeneration (biallelic); Disorders of mitochondrial DNA maintenance and integrity; Mitochondrial DNA Depletion Syndrome (biallelic); Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); 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) to Mitochondrial Membrane Protein-Associated Neurodegeneration (biallelic); Disorders of mitochondrial DNA maintenance and integrity; Mitochondrial DNA Depletion Syndrome (biallelic); Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); 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)
Likely inborn error of metabolism - targeted testing not possible v1.43 SLC25A4 Rebecca Foulger Phenotypes for gene: SLC25A4 were changed from Progressive External Ophthalmoplegia with Mitochondrial DNADeletions; 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 to Progressive External Ophthalmoplegia with Mitochondrial DNADeletions; 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
Likely inborn error of metabolism - targeted testing not possible v1.37 FXN Eleanor Williams Phenotypes for gene: FXN were changed from Friedreich ataxia, 229300Friedreich ataxia with retained reflexes, 229300; Hereditary ataxia; Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) to Friedreich ataxia, 229300; Friedreich ataxia with retained reflexes, 229300; Hereditary ataxia; Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only))
Likely inborn error of metabolism - targeted testing not possible v1.32 SLC17A5 Louise Daugherty Phenotypes for gene: SLC17A5 were changed from Salla disease, 604369 to Salla disease, 604369; Sialic acid storage disorder, infantile, 269920
Likely inborn error of metabolism - targeted testing not possible v1.29 PHKA1 Louise Daugherty Phenotypes for gene: PHKA1 were changed from to Muscle glycogenosis, 300559
Likely inborn error of metabolism - targeted testing not possible v1.27 CLN3 Louise Daugherty Phenotypes for gene: CLN3 were changed from to Ceroid lipofuscinosis, neuronal, 3, 204200
Likely inborn error of metabolism - targeted testing not possible v1.26 CLN5 Louise Daugherty Phenotypes for gene: CLN5 were changed from to Ceroid lipofuscinosis, neuronal, 5, 256731
Likely inborn error of metabolism - targeted testing not possible v1.24 CTSD Louise Daugherty Phenotypes for gene: CTSD were changed from to Ceroid lipofuscinosis, neuronal, 10, 610127
Likely inborn error of metabolism - targeted testing not possible v1.23 DNAJC5 Louise Daugherty Phenotypes for gene: DNAJC5 were changed from to Ceroid lipofuscinosis, neuronal, 4, Parry type, 162350
Likely inborn error of metabolism - targeted testing not possible v1.20 FUCA1 Louise Daugherty Phenotypes for gene: FUCA1 were changed from to Fucosidosis, 230000
Likely inborn error of metabolism - targeted testing not possible v1.15 GM2A Louise Daugherty Phenotypes for gene: GM2A were changed from to GM2-gangliosidosis, AB variant, 272750
Likely inborn error of metabolism - targeted testing not possible v1.10 MFSD8 Louise Daugherty Phenotypes for gene: MFSD8 were changed from to Ceroid lipofuscinosis, neuronal, 7 61095
Likely inborn error of metabolism - targeted testing not possible v1.9 CLN6 Louise Daugherty Phenotypes for gene: CLN6 were changed from to Ceroid lipofuscinosis, neuronal, 6, 601780; Ceroid lipofuscinosis, neuronal, Kufs type, adult onset, 204300
Likely inborn error of metabolism - targeted testing not possible v1.7 CP Louise Daugherty Phenotypes for gene: CP were changed from Cerebellar ataxia to Cerebellar ataxia, 604290; Hemosiderosis, systemic, due to aceruloplasminemia, 604290
Likely inborn error of metabolism - targeted testing not possible v1.6 CYP27A1 Louise Daugherty Phenotypes for gene: CYP27A1 were changed from Cerebrotendinous xanthomatosis to Cerebrotendinous xanthomatosis, 213700
Likely inborn error of metabolism - targeted testing not possible v1.5 GLRA1 Louise Daugherty Phenotypes for gene: GLRA1 were changed from Hyperekplexia, hereditary 1, autosomal dominant or recessive 149400 to Hyperekplexia, hereditary 1, 149400
Likely inborn error of metabolism - targeted testing not possible v1.4 HEXA Louise Daugherty Phenotypes for gene: HEXA were changed from GM2-gangliosidosis, several forms to GM2-gangliosidosis, several forms, 272800; Tay-Sachs disease, 272800
Likely inborn error of metabolism - targeted testing not possible v1.0 Ellen McDonagh promoted panel to version 1.0
Likely inborn error of metabolism - targeted testing not possible v0.24 ISCA-37440-Loss Ellen McDonagh Region: isca-37440-loss has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v0.24 FXN_GAA Louise Daugherty Classified STR: FXN_GAA as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v0.24 FXN_GAA Louise Daugherty Str: fxn_gaa has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v0.22 DMPK_CTG Louise Daugherty Classified STR: DMPK_CTG as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v0.22 DMPK_CTG Louise Daugherty Str: dmpk_ctg has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v0.19 TIMM50 Sarah Leigh Classified gene: TIMM50 as Amber List (moderate evidence)
Likely inborn error of metabolism - targeted testing not possible v0.19 TIMM50 Sarah Leigh Added comment: Comment on list classification: Based on reviewer's rating and published evidence.
Likely inborn error of metabolism - targeted testing not possible v0.19 TIMM50 Sarah Leigh Gene: timm50 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism - targeted testing not possible v0.17 MRPS34 Sarah Leigh Classified gene: MRPS34 as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v0.17 MRPS34 Sarah Leigh Added comment: Comment on list classification: Based on reviewer's rating and published evidence.
Likely inborn error of metabolism - targeted testing not possible v0.17 MRPS34 Sarah Leigh Gene: mrps34 has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v0.16 MRPS34 Sarah Leigh gene: MRPS34 was added
gene: MRPS34 was added to Inborn errors of metabolism. Sources: Expert Review,Literature
Mode of inheritance for gene: MRPS34 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRPS34 were set to 28777931
Phenotypes for gene: MRPS34 were set to Combined oxidative phosphorylation deficiency 32 617664
Review for gene: MRPS34 was set to GREEN
Added comment: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 4 variants reported in 3 unrelated cases.
(Six individuals from four unrelated families reported in the literature with bi-allelic variants in this gene. Zornitza Stark (Australian Genomics), 30 Aug 2018)
Sources: Expert Review, Literature
Likely inborn error of metabolism - targeted testing not possible v0.15 FDXR Sarah Leigh Classified gene: FDXR as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v0.15 FDXR Sarah Leigh Added comment: Comment on list classification: Based on reviewer's rating and published evidence.
Likely inborn error of metabolism - targeted testing not possible v0.15 FDXR Sarah Leigh Gene: fdxr has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v0.13 C1QBP Sarah Leigh Classified gene: C1QBP as Green List (high evidence)
Likely inborn error of metabolism - targeted testing not possible v0.13 C1QBP Sarah Leigh Gene: c1qbp has been classified as Green List (High Evidence).
Likely inborn error of metabolism - targeted testing not possible v0.9 Louise Daugherty List of related panels changed from Likely inborn error of metabolism - targeted testing not possible; GMS R98 to Likely inborn error of metabolism - targeted testing not possible
Likely inborn error of metabolism - targeted testing not possible v0.4 ISCA-37440-Loss Ellen McDonagh Region: ISCA-37440-Loss was added
Region: ISCA-37440-Loss was added to Inborn errors of metabolism. Sources: 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 18234729; 11524703; 16385448
Phenotypes for Region: ISCA-37440-Loss were set to hyperphagia; lactic acidemia; mild/moderate mental retardation; Hypotonia-cystinuria syndrome (HCS); 606407; failure to thrive; nephrolithiasis; rapid weight gain in late childhood; minor facial dysmorphism; growth hormone deficiency; facial dysmorphism; respiratory chain complex IV deficiency; cystinuria; neonatal seizures; 2p21 deletion syndrome; hypotonia; severe somatic and developmental delay
Likely inborn error of metabolism - targeted testing not possible v0.4 WARS2 Ellen McDonagh gene: WARS2 was added
gene: WARS2 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: WARS2 was set to Unknown
Phenotypes for gene: WARS2 were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 TRMT10C Ellen McDonagh gene: TRMT10C was added
gene: TRMT10C was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: TRMT10C was set to Unknown
Phenotypes for gene: TRMT10C were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 TRIT1 Ellen McDonagh gene: TRIT1 was added
gene: TRIT1 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: TRIT1 was set to Unknown
Phenotypes for gene: TRIT1 were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); No OMIM phenotype
Likely inborn error of metabolism - targeted testing not possible v0.4 TRAP1 Ellen McDonagh gene: TRAP1 was added
gene: TRAP1 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: TRAP1 was set to Unknown
Publications for gene: TRAP1 were set to PMID: 24152966 - recessive mutations reported in 2 families with CAKUT, and 3 families with VACTERL.
Likely inborn error of metabolism - targeted testing not possible v0.4 SRRT Ellen McDonagh gene: SRRT was added
gene: SRRT was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: SRRT was set to Unknown
Phenotypes for gene: SRRT were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 QRSL1 Ellen McDonagh gene: QRSL1 was added
gene: QRSL1 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: QRSL1 was set to Unknown
Phenotypes for gene: QRSL1 were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 QARS Ellen McDonagh gene: QARS was added
gene: QARS was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: QARS was set to Unknown
Phenotypes for gene: QARS were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 PTCD1 Ellen McDonagh gene: PTCD1 was added
gene: PTCD1 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: PTCD1 was set to Unknown
Phenotypes for gene: PTCD1 were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 MRPS7 Ellen McDonagh gene: MRPS7 was added
gene: MRPS7 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: MRPS7 was set to Unknown
Phenotypes for gene: MRPS7 were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 MRPL44 Ellen McDonagh gene: MRPL44 was added
gene: MRPL44 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: MRPL44 was set to Unknown
Phenotypes for gene: MRPL44 were set to ?Combined oxidative phosphorylation deficiency 16, 615395; Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 MRPL12 Ellen McDonagh gene: MRPL12 was added
gene: MRPL12 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: MRPL12 was set to Unknown
Phenotypes for gene: MRPL12 were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); No OMIM phenotype
Likely inborn error of metabolism - targeted testing not possible v0.4 LETM1 Ellen McDonagh gene: LETM1 was added
gene: LETM1 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: LETM1 was set to Unknown
Phenotypes for gene: LETM1 were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 GFM2 Ellen McDonagh gene: GFM2 was added
gene: GFM2 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: GFM2 was set to Unknown
Phenotypes for gene: GFM2 were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 GATC Ellen McDonagh gene: GATC was added
gene: GATC was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: GATC was set to Unknown
Phenotypes for gene: GATC were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 GATB Ellen McDonagh gene: GATB was added
gene: GATB was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: GATB was set to Unknown
Phenotypes for gene: GATB were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 ECSIT Ellen McDonagh gene: ECSIT was added
gene: ECSIT was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: ECSIT was set to Unknown
Phenotypes for gene: ECSIT were set to No OMIM phenotype; Isolated complex I deficiency
Likely inborn error of metabolism - targeted testing not possible v0.4 STS Ellen McDonagh gene: STS was added
gene: STS was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: STS was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: STS were set to 27604308
Phenotypes for gene: STS were set to X-linked ichthyosis (Other disorders in the metabolism of sterols); Autosomal recessive congenital ichthyosis
Likely inborn error of metabolism - targeted testing not possible v0.4 NSDHL Ellen McDonagh gene: NSDHL was added
gene: NSDHL was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: NSDHL was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: NSDHL were set to 27604308
Phenotypes for gene: NSDHL were set to Congenital hemidysplasia with ichtyosiform erythroderma and limb defects (Disorders of sterol biosynthesis); CHILD syndrome 308050 XLD; CK syndrome 300831 XLR
Likely inborn error of metabolism - targeted testing not possible v0.4 EBP Ellen McDonagh gene: EBP was added
gene: EBP was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: EBP was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: EBP were set to 27604308
Phenotypes for gene: EBP were set to MEND syndrome 300960 XLR; Chondrodysplasia punctata, X-linked dominant 302960 XLD; X-linked dominant chondrodysplasia punctata 2 (Disorders of sterol biosynthesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 COX7B Ellen McDonagh Added phenotypes Linear skin defects with multiple congenital anomalies; Complex IV (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits); Isolated complex IV deficiency; Aplasia cutis congenita, reticulolinear, with microcephaly, facial dysmorphism and other congenital anomalies, 300887; MICROPHTHALMIA WITH LINEAR SKIN LESIONS for gene: COX7B
Publications for gene COX7B were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 COX7B Ellen McDonagh gene: COX7B was added
gene: COX7B was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: COX7B was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: COX7B were set to Linear skin defects with multiple congenital anomalies; Isolated complex IV deficiency; Aplasia cutis congenita, reticulolinear, with microcephaly, facial dysmorphism and other congenital anomalies, 300887; MICROPHTHALMIA WITH LINEAR SKIN LESIONS
Likely inborn error of metabolism - targeted testing not possible v0.4 ALAS2 Ellen McDonagh gene: ALAS2 was added
gene: ALAS2 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: ALAS2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: ALAS2 were set to 27604308
Phenotypes for gene: ALAS2 were set to Erythropoietic protoporphyria, mild variant; X-linked sideroblastic anaemia (XLSA) (Porphyrias with acute painful photosensitivity); X-linked dominant protoporphyria (Porphyrias with acute painful photosensitivity)
Likely inborn error of metabolism - targeted testing not possible v0.4 ABCB7 Ellen McDonagh Added phenotypes Disorders of iron homeostasis; congenital cerebellar hypoplasia/atrophy (PMID: 26242992).; Anemia, sideroblastic, with ataxia; Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) for gene: ABCB7
Publications for gene ABCB7 were changed from PMID: 26242992; 17192398; 22398176 to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 ABCB7 Ellen McDonagh gene: ABCB7 was added
gene: ABCB7 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: ABCB7 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: ABCB7 were set to PMID: 26242992; 17192398; 22398176
Phenotypes for gene: ABCB7 were set to congenital cerebellar hypoplasia/atrophy (PMID: 26242992).; Anemia, sideroblastic, with ataxia; Disorders of iron homeostasis
Likely inborn error of metabolism - targeted testing not possible v0.4 TIMM8A Ellen McDonagh Added phenotypes Mohr-Tranebjaerg syndrome, 304700; Jensen syndrome, 311150; Disorders of the mitochondrial import system; Disorders of mitochondrial protein import (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Deafness, X-linked 1, progressive for gene: TIMM8A
Publications for gene TIMM8A were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 TIMM8A Ellen McDonagh gene: TIMM8A was added
gene: TIMM8A was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: TIMM8A was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: TIMM8A were set to Mohr-Tranebjaerg syndrome, 304700; Jensen syndrome, 311150; Disorders of the mitochondrial import system; Deafness, X-linked 1, progressive
Likely inborn error of metabolism - targeted testing not possible v0.4 PIGA Ellen McDonagh Added phenotypes PIGA-CDG (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation); Multiple congenital anomalies-hypotonia-seizures syndrome 2 300868 for gene: PIGA
Publications for gene PIGA were changed from 25885527 to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 PIGA Ellen McDonagh gene: PIGA was added
gene: PIGA was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PIGA was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PIGA were set to 25885527
Phenotypes for gene: PIGA were set to Multiple congenital anomalies-hypotonia-seizures syndrome 2 300868; PIGA-CDG (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation)
Likely inborn error of metabolism - targeted testing not possible v0.4 OCRL Ellen McDonagh gene: OCRL was added
gene: OCRL was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: OCRL was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: OCRL were set to 27604308
Phenotypes for gene: OCRL were set to Lowe syndrome (Disorders of amino acid transport); Renal tract calcification (or Nephrolithiasis/nephrocalcinosis); Intellectual disability; Intellectual_disability; Cataracts
Likely inborn error of metabolism - targeted testing not possible v0.4 MAGT1 Ellen McDonagh Added phenotypes Immunodeficiency, X-linked, with magnesium defect, Epstein-Barr virus infection and neoplasia 300853; IAP-CDG (Disorders of protein N-glycosylation) for gene: MAGT1
Publications for gene MAGT1 were changed from 27604308 to 27604308; 27393411
Likely inborn error of metabolism - targeted testing not possible v0.4 IDS Ellen McDonagh gene: IDS was added
gene: IDS was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: IDS was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: IDS were set to 27604308
Phenotypes for gene: IDS were set to MUCOPOLYSACCHARIDOSIS TYPE 2; MPS II, Hunter disease (Mucopolysaccharidoses); Mucopolysaccharidosis II, 309900; Mucopolysaccharidosis Type II
Likely inborn error of metabolism - targeted testing not possible v0.4 ARSE Ellen McDonagh gene: ARSE was added
gene: ARSE was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: ARSE was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: ARSE were set to Chondrodysplasia punctata, X-linked recessive 302950
Likely inborn error of metabolism - targeted testing not possible v0.4 AIFM1 Ellen McDonagh Added phenotypes Disorders of mitochondrial apoptosis; Miscellaneous disorders/unknown function (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Cowchock syndrome, 310490; Combined oxidative phosphorylation deficiency 6, 300816 for gene: AIFM1
Publications for gene AIFM1 were changed from PMID: 20362274 (two related males); PMID: 23217327 to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 AIFM1 Ellen McDonagh gene: AIFM1 was added
gene: AIFM1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: AIFM1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: AIFM1 were set to PMID: 20362274 (two related males); PMID: 23217327
Phenotypes for gene: AIFM1 were set to Disorders of mitochondrial apoptosis; Cowchock syndrome, 310490; Combined oxidative phosphorylation deficiency 6, 300816
Likely inborn error of metabolism - targeted testing not possible v0.4 TDO2 Ellen McDonagh gene: TDO2 was added
gene: TDO2 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: TDO2 was set to Unknown
Publications for gene: TDO2 were set to 27604308
Phenotypes for gene: TDO2 were set to No OMIM number; Tryptophanaemia (Disorders of histidine, tryptophan or lysine metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 TARS2 Ellen McDonagh gene: TARS2 was added
gene: TARS2 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: TARS2 was set to Unknown
Publications for gene: TARS2 were set to PMID: 24827421 - Compound heterozygous variants in TARS2 were reported in the proband and his affected sister - a missense mutation (c.845C>T, p.Pro282Leu) and a nucleotide change in position +3 of intron 6 (g.4255A>G, c.695+3A>G). The parents carrying one of the variants, one unaffected sister carried one variant, and the other unaffected sibling carried neither.
Phenotypes for gene: TARS2 were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); ?Combined oxidative phosphorylation deficiency 21, 615918
Likely inborn error of metabolism - targeted testing not possible v0.4 PTPRZ1 Ellen McDonagh gene: PTPRZ1 was added
gene: PTPRZ1 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: PTPRZ1 was set to Unknown
Publications for gene: PTPRZ1 were set to 27604308
Phenotypes for gene: PTPRZ1 were set to Hyperlysinaemia (Disorders of histidine, tryptophan or lysine metabolism); {H. pylori infection, susceptibility to} 600263
Likely inborn error of metabolism - targeted testing not possible v0.4 PEX11A Ellen McDonagh gene: PEX11A was added
gene: PEX11A was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: PEX11A was set to Unknown
Publications for gene: PEX11A were set to 25177298; 10716247; 25608554; 11839773
Phenotypes for gene: PEX11A were set to Zellweger syndrome; peroxisome proliferation; mild peroxisomal biogenesis defect
Likely inborn error of metabolism - targeted testing not possible v0.4 HYKK Ellen McDonagh gene: HYKK was added
gene: HYKK was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: HYKK was set to Unknown
Publications for gene: HYKK were set to 27604308
Phenotypes for gene: HYKK were set to Hydroxylysinuria (Disorders of histidine, tryptophan or lysine metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 GLS Ellen McDonagh Added phenotypes Glucosidase 1 deficiency (Disorders of protein N-glycosylation) for gene: GLS
Likely inborn error of metabolism - targeted testing not possible v0.4 GLS Ellen McDonagh gene: GLS was added
gene: GLS was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: GLS was set to Unknown
Publications for gene: GLS were set to 27604308
Phenotypes for gene: GLS were set to Glucosidase 1 deficiency (Disorders of protein N-glycosylation)
Likely inborn error of metabolism - targeted testing not possible v0.4 GALNT12 Ellen McDonagh Mode of inheritance for gene GALNT12 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Unknown
Added phenotypes (GALNT12-CDG (Disorders of protein O-glycosylation, O-N-acetylgalactosaminylglycan synthesis deficiencies)); GALNT12-CDG (Disorders of protein O-glycosylation, O-N-acetylgalactosaminylglycan synthesis deficiencies); {Colorectal cancer, susceptibility to, 1} 608812 for gene: GALNT12
Likely inborn error of metabolism - targeted testing not possible v0.4 FDX2 Ellen McDonagh gene: FDX2 was added
gene: FDX2 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: FDX2 was set to Unknown
Phenotypes for gene: FDX2 were set to No OMIM phenotype?Mitochondrial myopathy with lactic acidosis, association with, 255125
Likely inborn error of metabolism - targeted testing not possible v0.4 FBP2 Ellen McDonagh gene: FBP2 was added
gene: FBP2 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: FBP2 was set to Unknown
Phenotypes for gene: FBP2 were set to isolated lactic acidosis
Likely inborn error of metabolism - targeted testing not possible v0.4 DMGDH Ellen McDonagh gene: DMGDH was added
gene: DMGDH was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: DMGDH was set to Unknown
Publications for gene: DMGDH were set to 27604308; 18937046 - functional study expressing the variant form in E.coli showed a decrease in activity; 11231903 - case study
Phenotypes for gene: DMGDH were set to Dimethylglycine dehydrogenase deficiency 605850; Dimethylglycinuria (Disorders and variants of enzymes that oxidise xenobiotics other than cytochrome P450)
Likely inborn error of metabolism - targeted testing not possible v0.4 CNDP1 Ellen McDonagh gene: CNDP1 was added
gene: CNDP1 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: CNDP1 was set to Unknown
Publications for gene: CNDP1 were set to 27604308
Phenotypes for gene: CNDP1 were set to Carnosinaemia (Other disorders of peptide metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 BCAT2 Ellen McDonagh gene: BCAT2 was added
gene: BCAT2 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: BCAT2 was set to Unknown
Publications for gene: BCAT2 were set to 27604308
Phenotypes for gene: BCAT2 were set to Branched-chain amino acid transferase (Disorder of branched-chain amino acid metabolism not classified as organic aciduria)
Likely inborn error of metabolism - targeted testing not possible v0.4 BCAT1 Ellen McDonagh gene: BCAT1 was added
gene: BCAT1 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: BCAT1 was set to Unknown
Publications for gene: BCAT1 were set to 27604308
Phenotypes for gene: BCAT1 were set to Branched-chain amino acid transferase (Disorder of branched-chain amino acid metabolism not classified as organic aciduria)
Likely inborn error of metabolism - targeted testing not possible v0.4 ATAD3B Ellen McDonagh gene: ATAD3B was added
gene: ATAD3B was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: ATAD3B was set to Unknown
Phenotypes for gene: ATAD3B were set to Influence on AIDS progression; No OMIM phenotype
Likely inborn error of metabolism - targeted testing not possible v0.4 ARSG Ellen McDonagh gene: ARSG was added
gene: ARSG was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: ARSG was set to Unknown
Publications for gene: ARSG were set to 26975023; 20679209; 25452429
Phenotypes for gene: ARSG were set to neuronal ceroid lipofuscinosis
Likely inborn error of metabolism - targeted testing not possible v0.4 C1GALT1C1 Ellen McDonagh Mode of inheritance for gene C1GALT1C1 was changed from Other - please specifiy in evaluation comments to Other - please specify in evaluation comments
Added phenotypes COSMC-CDG (Disorders of protein O-glycosylation, O-N-acetylgalactosaminylglycan synthesis deficiencies); Tn polyagglutination syndrome, somatic 300622 for gene: C1GALT1C1
Publications for gene C1GALT1C1 were changed from 27604308 to 27604308; 19778426; 27536663
Likely inborn error of metabolism - targeted testing not possible v0.4 SPTLC2 Ellen McDonagh gene: SPTLC2 was added
gene: SPTLC2 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: SPTLC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPTLC2 were set to 27604308
Phenotypes for gene: SPTLC2 were set to Charcot-Marie-Tooth disease; Serine palmitoyl transferase deficiency (Disorders of complex lipid synthesis); Familial dysautonomia
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC40A1 Ellen McDonagh gene: SLC40A1 was added
gene: SLC40A1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: SLC40A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC40A1 were set to 27604308; 11518736; 11431687; 10471458
Phenotypes for gene: SLC40A1 were set to Hemochromatosis, type 4 606069 (Disorder of iron metabolism); Hereditary haemochromatosis Type 4 (Disorder of iron metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 LDLR Ellen McDonagh gene: LDLR was added
gene: LDLR was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: LDLR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LDLR were set to 27604308
Phenotypes for gene: LDLR were set to Familial hypercholesterolaemia; Disorder of low density lipoprotein receptor (Inherited hypercholesterolaemias)
Likely inborn error of metabolism - targeted testing not possible v0.4 HAL Ellen McDonagh gene: HAL was added
gene: HAL was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: HAL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HAL were set to 27604308
Phenotypes for gene: HAL were set to Histidinaemia (Disorders of histidine, tryptophan or lysine metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 GARS Ellen McDonagh Added phenotypes Charcot-Marie-Tooth disease, type 2D; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Neuropathy, distal hereditary motor, type VA for gene: GARS
Likely inborn error of metabolism - targeted testing not possible v0.4 GARS Ellen McDonagh gene: GARS was added
gene: GARS was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: GARS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: GARS were set to Charcot-Marie-Tooth disease, type 2D; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Neuropathy, distal hereditary motor, type VA
Likely inborn error of metabolism - targeted testing not possible v0.4 GALNT12 Ellen McDonagh gene: GALNT12 was added
gene: GALNT12 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: GALNT12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GALNT12 were set to 27604308
Phenotypes for gene: GALNT12 were set to GALNT12-CDG (Disorders of protein O-glycosylation, O-N-acetylgalactosaminylglycan synthesis deficiencies); {Colorectal cancer, susceptibility to, 1} 608812
Likely inborn error of metabolism - targeted testing not possible v0.4 DNA2 Ellen McDonagh Added phenotypes Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 6; 615156; Disorders of mitochondrial DNA maintenance and integrity for gene: DNA2
Likely inborn error of metabolism - targeted testing not possible v0.4 DNA2 Ellen McDonagh gene: DNA2 was added
gene: DNA2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: DNA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: DNA2 were set to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 6; 615156; Disorders of mitochondrial DNA maintenance and integrity
Likely inborn error of metabolism - targeted testing not possible v0.4 CHCHD10 Ellen McDonagh Added phenotypes Frontotemporal dementia and/or amyotrophic lateral sclerosis 2; ?Myopathy, isolated mitochondrial, autosomal dominant, 616209; Spinal muscular atrophy, Jokela type for gene: CHCHD10
Likely inborn error of metabolism - targeted testing not possible v0.4 CHCHD10 Ellen McDonagh gene: CHCHD10 was added
gene: CHCHD10 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: CHCHD10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CHCHD10 were set to Frontotemporal dementia and/or amyotrophic lateral sclerosis 2; ?Myopathy, isolated mitochondrial, autosomal dominant, 616209; Spinal muscular atrophy, Jokela type
Likely inborn error of metabolism - targeted testing not possible v0.4 CETP Ellen McDonagh gene: CETP was added
gene: CETP was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: CETP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CETP were set to 27604308
Phenotypes for gene: CETP were set to [High density lipoprotein cholesterol level QTL 10] 143470; Familial hyperalphalipoproteinaemia (Disorders of high density lipoprotein metabolism); Hyperalphalipoproteinemia 143470
Likely inborn error of metabolism - targeted testing not possible v0.4 UROD Ellen McDonagh gene: UROD was added
gene: UROD was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: UROD was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: UROD were set to 27604308
Phenotypes for gene: UROD were set to Porphyria cutanea tarda (Porphyrias with erosive photodermatosis)
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC25A4 Ellen McDonagh Added phenotypes Progressive External Ophthalmoplegia with Mitochondrial DNADeletions; 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 for gene: SLC25A4
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC25A4 Ellen McDonagh gene: SLC25A4 was added
gene: SLC25A4 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: SLC25A4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SLC25A4 were set to 27604308
Phenotypes for gene: SLC25A4 were set to Progressive External Ophthalmoplegia with Mitochondrial DNADeletions; Disorders of mitochondrial protein transport; Disorders of mitochondrial DNA maintenance and integrity; Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Progressive external ophthalmoplegia with mitochondrial DNA deletions 3, 609283Mitochondrial DNA depletion syndrome 12 (cardiomyopathic type), 615418
Likely inborn error of metabolism - targeted testing not possible v0.4 POLG2 Ellen McDonagh Added phenotypes Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4,610131; Disorders of mitochondrial DNA maintenance and integrity; Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions for gene: POLG2
Publications for gene POLG2 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 POLG2 Ellen McDonagh gene: POLG2 was added
gene: POLG2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: POLG2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: POLG2 were set to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4,610131; Disorders of mitochondrial DNA maintenance and integrity; Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions
Likely inborn error of metabolism - targeted testing not possible v0.4 FXYD2 Ellen McDonagh gene: FXYD2 was added
gene: FXYD2 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: FXYD2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FXYD2 were set to 27604308
Phenotypes for gene: FXYD2 were set to Hypomagnesemia 2, renal 154020; Hypomagnesaemia type 2, renal (Disorder of magnesium metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 MT-TE Ellen McDonagh Added phenotypes MYOPATHY, MITOCHONDRIAL, WITH DIABETES MELLITUS; DIABETES AND DEAFNESS, MATERNALLY INHERITED; MITOCHONDRIAL MYOPATHY, INFANTILE, TRANSIENT for gene: MT-TE
Likely inborn error of metabolism - targeted testing not possible v0.4 MT-TE Ellen McDonagh gene: MT-TE was added
gene: MT-TE was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene gene: MT-TE was set to MITOCHONDRIAL
Phenotypes for gene: MT-TE were set to MYOPATHY, MITOCHONDRIAL, WITH DIABETES MELLITUS; DIABETES AND DEAFNESS, MATERNALLY INHERITED; MITOCHONDRIAL MYOPATHY, INFANTILE, TRANSIENT
Likely inborn error of metabolism - targeted testing not possible v0.4 MT-RNR1 Ellen McDonagh Added phenotypes DEAFNESS, AMINOGLYCOSIDE-INDUCED; DEAFNESS, NONSYNDROMIC SENSORINEURAL, MITOCHONDRIAL; AUDITORY NEUROPATHY; CARDIOMYOPATHY, RESTRICTIVE for gene: MT-RNR1
Likely inborn error of metabolism - targeted testing not possible v0.4 MT-RNR1 Ellen McDonagh gene: MT-RNR1 was added
gene: MT-RNR1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene gene: MT-RNR1 was set to MITOCHONDRIAL
Phenotypes for gene: MT-RNR1 were set to DEAFNESS, AMINOGLYCOSIDE-INDUCED; DEAFNESS, NONSYNDROMIC SENSORINEURAL, MITOCHONDRIAL; AUDITORY NEUROPATHY; CARDIOMYOPATHY, RESTRICTIVE
Likely inborn error of metabolism - targeted testing not possible v0.4 MT-ND6 Ellen McDonagh Added phenotypes LEBER OPTIC ATROPHY AND DYSTONIA; STRIATAL NECROSIS, BILATERAL, WITH DYSTONIA; MELAS SYNDROME; LEBER OPTIC ATROPHY; LEIGH SYNDROME DUE TO MITOCHONDRIAL COMPLEX I DEFICIENCY for gene: MT-ND6
Likely inborn error of metabolism - targeted testing not possible v0.4 MT-ND6 Ellen McDonagh gene: MT-ND6 was added
gene: MT-ND6 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene gene: MT-ND6 was set to MITOCHONDRIAL
Phenotypes for gene: MT-ND6 were set to LEBER OPTIC ATROPHY AND DYSTONIA; STRIATAL NECROSIS, BILATERAL, WITH DYSTONIA; MELAS SYNDROME; LEBER OPTIC ATROPHY; LEIGH SYNDROME DUE TO MITOCHONDRIAL COMPLEX I DEFICIENCY
Likely inborn error of metabolism - targeted testing not possible v0.4 MT-CYB Ellen McDonagh Added phenotypes CARDIOMYOPATHY, INFANTILE HISTIOCYTOID; ENCEPHALOMYOPATHY, MITOCHONDRIAL; MULTISYSTEM DISORDER; EXERCISE INTOLERANCE; EXERCISE INTOLERANCE, CARDIOMYOPATHY, AND SEPTOOPTIC DYSPLASIA; PARKINSONISM/MELAS OVERLAP SYNDROME; LEBER OPTIC ATROPHY for gene: MT-CYB
Likely inborn error of metabolism - targeted testing not possible v0.4 MT-CYB Ellen McDonagh gene: MT-CYB was added
gene: MT-CYB was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene gene: MT-CYB was set to MITOCHONDRIAL
Phenotypes for gene: MT-CYB were set to CARDIOMYOPATHY, INFANTILE HISTIOCYTOID; ENCEPHALOMYOPATHY, MITOCHONDRIAL; MULTISYSTEM DISORDER; EXERCISE INTOLERANCE; EXERCISE INTOLERANCE, CARDIOMYOPATHY, AND SEPTOOPTIC DYSPLASIA; PARKINSONISM/MELAS OVERLAP SYNDROME; LEBER OPTIC ATROPHY
Likely inborn error of metabolism - targeted testing not possible v0.4 MT-CO3 Ellen McDonagh gene: MT-CO3 was added
gene: MT-CO3 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene gene: MT-CO3 was set to MITOCHONDRIAL
Publications for gene: MT-CO3 were set to LEBER OPTIC ATROPHY; SEIZURES AND LACTIC ACIDOSIS; MITOCHONDRIAL COMPLEX IV DEFICIENCY
Likely inborn error of metabolism - targeted testing not possible v0.4 MT-CO1 Ellen McDonagh Added phenotypes CYTOCHROME c OXIDASE I DEFICIENCY; SIDEROBLASTIC ANEMIA, ACQUIRED IDIOPATHIC; LEBER OPTIC ATROPHY; MYOGLOBINURIA, RECURRENT; CYTOCHROME c OXIDASE DEFICIENCY for gene: MT-CO1
Likely inborn error of metabolism - targeted testing not possible v0.4 MT-CO1 Ellen McDonagh gene: MT-CO1 was added
gene: MT-CO1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene gene: MT-CO1 was set to MITOCHONDRIAL
Phenotypes for gene: MT-CO1 were set to CYTOCHROME c OXIDASE I DEFICIENCY; SIDEROBLASTIC ANEMIA, ACQUIRED IDIOPATHIC; LEBER OPTIC ATROPHY; MYOGLOBINURIA, RECURRENT; CYTOCHROME c OXIDASE DEFICIENCY
Likely inborn error of metabolism - targeted testing not possible v0.4 MT-ATP8 Ellen McDonagh Added phenotypes BRAIN PSEUDOATROPHY, REVERSIBLE, VALPROATE-INDUCED, SUSCEPTIBILITY TO; CARDIOMYOPATHY, APICAL HYPERTROPHIC, AND NEUROPATHY; CARDIOMYOPATHY, INFANTILE HYPERTROPHIC for gene: MT-ATP8
Likely inborn error of metabolism - targeted testing not possible v0.4 MT-ATP8 Ellen McDonagh gene: MT-ATP8 was added
gene: MT-ATP8 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene gene: MT-ATP8 was set to MITOCHONDRIAL
Phenotypes for gene: MT-ATP8 were set to BRAIN PSEUDOATROPHY, REVERSIBLE, VALPROATE-INDUCED, SUSCEPTIBILITY TO; CARDIOMYOPATHY, APICAL HYPERTROPHIC, AND NEUROPATHY; CARDIOMYOPATHY, INFANTILE HYPERTROPHIC
Likely inborn error of metabolism - targeted testing not possible v0.4 TWNK Ellen McDonagh Added phenotypes Mitochondrial Membrane Protein-Associated Neurodegeneration (biallelic); Disorders of mitochondrial DNA maintenance and integrity; Mitochondrial DNA Depletion Syndrome (biallelic); 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) for gene: TWNK
Likely inborn error of metabolism - targeted testing not possible v0.4 TWNK Ellen McDonagh gene: TWNK was added
gene: TWNK was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: TWNK was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TWNK were set to 27604308
Phenotypes for gene: TWNK were set to Mitochondrial Membrane Protein-Associated Neurodegeneration (biallelic); Disorders of mitochondrial DNA maintenance and integrity; Mitochondrial DNA Depletion Syndrome (biallelic); Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); 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)
Likely inborn error of metabolism - targeted testing not possible v0.4 SPTLC1 Ellen McDonagh gene: SPTLC1 was added
gene: SPTLC1 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: SPTLC1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SPTLC1 were set to 27604308
Phenotypes for gene: SPTLC1 were set to Charcot-Marie-Tooth disease; Serine palmitoyl transferase deficiency (Disorders of complex lipid synthesis); Familial dysautonomia
Likely inborn error of metabolism - targeted testing not possible v0.4 SPG7 Ellen McDonagh Added phenotypes Miscellaneous disorders/unknown function (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Spastic paraplegia 7, autosomal recessive, 607259; Disorders of mitochondrial DNA maintenance and integrity for gene: SPG7
Publications for gene SPG7 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 SPG7 Ellen McDonagh gene: SPG7 was added
gene: SPG7 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: SPG7 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: SPG7 were set to Spastic paraplegia 7, autosomal recessive, 607259; Disorders of mitochondrial DNA maintenance and integrity
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC2A1 Ellen McDonagh gene: SLC2A1 was added
gene: SLC2A1 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: SLC2A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SLC2A1 were set to 27604308
Phenotypes for gene: SLC2A1 were set to Intellectual disability; Early onset dystonia; Cataracts; Glucose transporter 1 deficiency (blood-brain barrier) (Disorders of glucose transport); Hereditary ataxia; Epileptic encephalopathy; Familial Genetic Generalised Epilepsies
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC16A1 Ellen McDonagh gene: SLC16A1 was added
gene: SLC16A1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: SLC16A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SLC16A1 were set to 26608392; 17701893
Phenotypes for gene: SLC16A1 were set to Hyperinsulinemic hypoglycemia, familial, 7; mainly ketosis with borderline reduction in glucose
Likely inborn error of metabolism - targeted testing not possible v0.4 SETX Ellen McDonagh gene: SETX was added
gene: SETX was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: SETX was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SETX were set to 27604308
Phenotypes for gene: SETX were set to Secondary CoQ10 deficiency (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Charcot-Marie-Tooth disease; Hereditary ataxia; Amyotrophic lateral sclerosis/motor neuron disease
Likely inborn error of metabolism - targeted testing not possible v0.4 SCARB1 Ellen McDonagh gene: SCARB1 was added
gene: SCARB1 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: SCARB1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SCARB1 were set to 27604308
Phenotypes for gene: SCARB1 were set to [High density lipoprotein cholesterol level QTL6] 610762; Scavenger receptor class B type I deficiency (Inherited hypolipidaemias)
Likely inborn error of metabolism - targeted testing not possible v0.4 RYR1 Ellen McDonagh gene: RYR1 was added
gene: RYR1 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: RYR1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: RYR1 were set to Rhabdomyolysis and metabolic muscle disorders
Likely inborn error of metabolism - targeted testing not possible v0.4 RRM2B Ellen McDonagh Added phenotypes Progressive external ophthalmoplegia with mitochondrial DNA deletions (autosomal dominant); Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy), 612075; Disorders of mitochondrial DNA maintenance and integrity; Mitochondrial DNA Depletion Syndrome (recessive); 5,613077Mitochondrial DNA depletion syndrome 8B (MNGIE type), 612075 for gene: RRM2B
Likely inborn error of metabolism - targeted testing not possible v0.4 RRM2B Ellen McDonagh gene: RRM2B was added
gene: RRM2B was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: RRM2B was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RRM2B were set to 27604308
Phenotypes for gene: RRM2B were set to 5,613077Mitochondrial DNA depletion syndrome 8B (MNGIE type), 612075; Mitochondrial DNA Depletion Syndrome (recessive); Mitochondrial Ribonucelotide Reductase subunit 2 deficiency (Disorders of purine metabolism); Progressive external ophthalmoplegia with mitochondrial DNA deletions (autosomal dominant); Disorders of mitochondrial DNA maintenance and integrity; Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy), 612075
Likely inborn error of metabolism - targeted testing not possible v0.4 POLG Ellen McDonagh Added phenotypes Progressive external ophthalmoplegia, autosomal dominant, 157640; Mitochondrial DNA depletion syndrome 4A (Alpers type), 203700; Progressive external ophthalmoplegia, autosomal recessive, 258450; Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions; Mitochondrial DNA depletion syndrome 4B (MNGIE type), 613662; Mitochondrial DNA depletion syndrome 4A (Alpers type); Mitochondrial DNA Depletion Syndrome; Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE), 607459 for gene: POLG
Publications for gene POLG were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 POLG Ellen McDonagh gene: POLG was added
gene: POLG was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: POLG was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: POLG were set to Progressive external ophthalmoplegia, autosomal dominant, 157640; Progressive external ophthalmoplegia, autosomal recessive, 258450; Mitochondrial DNA depletion syndrome 4A (Alpers type), 203700; Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions; Mitochondrial DNA depletion syndrome 4B (MNGIE type), 613662; Mitochondrial DNA Depletion Syndrome; Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE), 607459
Likely inborn error of metabolism - targeted testing not possible v0.4 MFN2 Ellen McDonagh Added phenotypes Charcot-Marie-Tooth disease, type 2A2, 609260; Disorders of mitochondrial dynamics, fusion and fission (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of mitochondrial DNA maintenance and integrity; Hereditary motor and sensory neuropathy VI, 601152 for gene: MFN2
Publications for gene MFN2 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 MAT1A Ellen McDonagh gene: MAT1A was added
gene: MAT1A was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: MAT1A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MAT1A were set to 27604308
Phenotypes for gene: MAT1A were set to Hypermethioninemia, persistent, autosomal dominant, due to methionine adenosyltransferase I/III deficiency
Likely inborn error of metabolism - targeted testing not possible v0.4 LBR Ellen McDonagh gene: LBR was added
gene: LBR was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: LBR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: LBR were set to 27604308
Phenotypes for gene: LBR were set to Greenberg skeletal dysplasia (Disorders of sterol biosynthesis); Unexplained skeletal dysplasia; Fetal hydrops
Likely inborn error of metabolism - targeted testing not possible v0.4 HPD Ellen McDonagh gene: HPD was added
gene: HPD was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: HPD was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: HPD were set to 27604308
Phenotypes for gene: HPD were set to Intellectual disability; 4-hydroxyphenylpyruvate dioxygenase deficiency (Disorders of phenylalanine or tyrosine metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 GLRA1 Ellen McDonagh gene: GLRA1 was added
gene: GLRA1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: GLRA1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: GLRA1 were set to Hyperekplexia, hereditary 1, autosomal dominant or recessive 149400
Likely inborn error of metabolism - targeted testing not possible v0.4 GCH1 Ellen McDonagh gene: GCH1 was added
gene: GCH1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: GCH1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GCH1 were set to 27604308
Phenotypes for gene: GCH1 were set to Dystonia, DOPA-responsive, with or without hyperphenylalaninemia
Likely inborn error of metabolism - targeted testing not possible v0.4 FGFR2 Ellen McDonagh gene: FGFR2 was added
gene: FGFR2 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: FGFR2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: FGFR2 were set to 27604308
Phenotypes for gene: FGFR2 were set to Bilateral microtia; Deafness and congenital structural abnormalities; Craniosynostosis syndromes phenotypes; Arthrogryposis; Choanal atresia; Antley-Bixler syndrome type without disordered steroidogenesis; Unexplained skeletal dysplasia
Likely inborn error of metabolism - targeted testing not possible v0.4 EXT2 Ellen McDonagh Added phenotypes Exostoses, multiple, type 2 133701; Multiple exostoses type II (Disorders of protein O-glycosylation, O-xylosylglycan synthesis deficiencies); ?Seizures, scoliosis, and macrocephaly syndrome 616682 for gene: EXT2
Publications for gene EXT2 were changed from 27604308 to 12417417
Likely inborn error of metabolism - targeted testing not possible v0.4 EXT2 Ellen McDonagh gene: EXT2 was added
gene: EXT2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: EXT2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: EXT2 were set to 27604308
Phenotypes for gene: EXT2 were set to Multiple exostoses type II (Disorders of protein O-glycosylation, O-xylosylglycan synthesis deficiencies); Exostoses, multiple, type 2 133701; ?Seizures, scoliosis, and macrocephaly syndrome 616682
Likely inborn error of metabolism - targeted testing not possible v0.4 DNM1L Ellen McDonagh Added phenotypes Encephalopahty, lethal, due to defective mitochondrial peroxisomal fission, 614388; Encephalopahty, lethal, due to defective mitochondrial peroxisomal fission; Disorders of mitochondrial dynamics, fusion and fission (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) for gene: DNM1L
Publications for gene DNM1L were changed from 17460227; PMID: 26825290 to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 DNM1L Ellen McDonagh gene: DNM1L was added
gene: DNM1L was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: DNM1L was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: DNM1L were set to 17460227; PMID: 26825290
Phenotypes for gene: DNM1L were set to Encephalopahty, lethal, due to defective mitochondrial peroxisomal fission, 614388
Likely inborn error of metabolism - targeted testing not possible v0.4 DHTKD1 Ellen McDonagh gene: DHTKD1 was added
gene: DHTKD1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: DHTKD1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: DHTKD1 were set to 27604308
Phenotypes for gene: DHTKD1 were set to 2-Oxoadipic aciduria (Disorders of histidine, tryptophan or lysine metabolism); 2-aminoadipic and 2-oxoadipic aciduria, 204750; 2-Aminoadipic aciduria (Disorders of histidine, tryptophan or lysine metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 CNNM2 Ellen McDonagh gene: CNNM2 was added
gene: CNNM2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: CNNM2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CNNM2 were set to 27604308
Phenotypes for gene: CNNM2 were set to Hypomagnesaemia type 6, renal (Disorder of magnesium metabolism); Hypomagnesemia 6, renal 613882; Hypomagnesemia, seizures, and mental retardation 616418
Likely inborn error of metabolism - targeted testing not possible v0.4 ATP8B1 Ellen McDonagh gene: ATP8B1 was added
gene: ATP8B1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: ATP8B1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ATP8B1 were set to 27604308
Phenotypes for gene: ATP8B1 were set to Cholestasis, progressive familial intrahepatic 1 211600; Cholestasis, benign recurrent intrahepatic 243300 AR; Cholestasis, intrahepatic, of pregnancy, 1 147480 AD; Byler disease (Disorders of bile acid metabolism and transport)
Likely inborn error of metabolism - targeted testing not possible v0.4 APOA1 Ellen McDonagh gene: APOA1 was added
gene: APOA1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: APOA1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: APOA1 were set to 27604308
Phenotypes for gene: APOA1 were set to Corneal clouding, autosomal recessive; Apolipoprotein A-I deficiency (Disorders of high density lipoprotein metabolism); ApoA-I and apoC-III deficiency, combined; Amyloidosis, 3 or more types 105200; Hypoalphalipoproteinemia 604091
Likely inborn error of metabolism - targeted testing not possible v0.4 ABCB4 Ellen McDonagh gene: ABCB4 was added
gene: ABCB4 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: ABCB4 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ABCB4 were set to 27604308
Phenotypes for gene: ABCB4 were set to Gallbladder disease 1 600803 AD, AR; Cholestasis, progressive familial intrahepatic 3 602347 AR; Progressive familial intrahepatic cholestasis type 3 (Disorders of bile acid metabolism and transport); Cholestasis, intrahepatic, of pregnancy, 3 614972 AD, AR
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC7A9 Ellen McDonagh gene: SLC7A9 was added
gene: SLC7A9 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: SLC7A9 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: SLC7A9 were set to 27604308; 24816252
Phenotypes for gene: SLC7A9 were set to Renal tract calcification (or Nephrolithiasis/nephrocalcinosis); Cystinuria (Disorders of amino acid transport)
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC3A1 Ellen McDonagh gene: SLC3A1 was added
gene: SLC3A1 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: SLC3A1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: SLC3A1 were set to 27604308
Phenotypes for gene: SLC3A1 were set to Renal tract calcification (or Nephrolithiasis/nephrocalcinosis); Cystinuria (Disorders of amino acid transport); Hypotonia-cystinuria syndrome (Disorders of amino acid transport)
Likely inborn error of metabolism - targeted testing not possible v0.4 OPA1 Ellen McDonagh Added phenotypes Optic atrophy plus syndrome, 125250; {Glaucoma, normal tension, susceptibility to}, 606657; Disorders of mitochondrial DNA maintenance and integrity; Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions; Optic atrophy 1, 165500; Mitochondrial DNA Depletion Syndrome; Disorders of mitochondrial dynamics, fusion and fission (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) for gene: OPA1
Publications for gene OPA1 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 OPA1 Ellen McDonagh gene: OPA1 was added
gene: OPA1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: OPA1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: OPA1 were set to Optic atrophy plus syndrome, 125250; {Glaucoma, normal tension, susceptibility to}, 606657; Disorders of mitochondrial DNA maintenance and integrity; Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions; Optic atrophy 1, 165500; Mitochondrial DNA Depletion Syndrome
Likely inborn error of metabolism - targeted testing not possible v0.4 GDAP1 Ellen McDonagh Added phenotypes Charcot Marie Tooth disease (CMT4A); Charcot-Marie-Tooth disease, type 4A; Charcot-Marie-Tooth disease, recessive intermediate, A; Charcot-Marie-Tooth disease, axonal, with vocal cord paresis; Charcot-Marie-Tooth disease, axonal, type 2K for gene: GDAP1
Publications for gene GDAP1 were changed from 11743579 to PMID: 11743579
Likely inborn error of metabolism - targeted testing not possible v0.4 GDAP1 Ellen McDonagh gene: GDAP1 was added
gene: GDAP1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: GDAP1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: GDAP1 were set to 11743579
Phenotypes for gene: GDAP1 were set to Charcot Marie Tooth disease (CMT4A); Charcot-Marie-Tooth disease, type 4A; Charcot-Marie-Tooth disease, recessive intermediate, A; Charcot-Marie-Tooth disease, axonal, with vocal cord paresis; Charcot-Marie-Tooth disease, axonal, type 2K
Likely inborn error of metabolism - targeted testing not possible v0.4 ALPL Ellen McDonagh gene: ALPL was added
gene: ALPL was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: ALPL was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: ALPL were set to 27604308
Phenotypes for gene: ALPL were set to Unexplained skeletal dysplasia; Osteogenesis Imperfecta; Craniosynostosis syndromes phenotypes; Hypophosphatasia (Disorders of pyridoxine metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 AFG3L2 Ellen McDonagh Added phenotypes Ataxia, spastic, 5, autosomal recessive, 614487; Miscellaneous disorders/unknown function (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Spinocerebellar ataxia 28, 610246; Disorders of mitochondrial DNA maintenance and integrity for gene: AFG3L2
Publications for gene AFG3L2 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 AFG3L2 Ellen McDonagh gene: AFG3L2 was added
gene: AFG3L2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: AFG3L2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Phenotypes for gene: AFG3L2 were set to Ataxia, spastic, 5, autosomal recessive, 614487; Spinocerebellar ataxia 28, 610246; Disorders of mitochondrial DNA maintenance and integrity
Likely inborn error of metabolism - targeted testing not possible v0.4 YARS2 Ellen McDonagh Added phenotypes Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Myopathy, lactic acidosis, and sideroblastic anemia 2, 613561 for gene: YARS2
Publications for gene YARS2 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 YARS2 Ellen McDonagh gene: YARS2 was added
gene: YARS2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: YARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: YARS2 were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Myopathy, lactic acidosis, and sideroblastic anemia 2, 613561
Likely inborn error of metabolism - targeted testing not possible v0.4 XYLT1 Ellen McDonagh Added phenotypes Desbuquois dysplasia 2 for gene: XYLT1
Likely inborn error of metabolism - targeted testing not possible v0.4 XYLT1 Ellen McDonagh gene: XYLT1 was added
gene: XYLT1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: XYLT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XYLT1 were set to 23982343; 24581741
Phenotypes for gene: XYLT1 were set to Desbuquois dysplasia 2
Likely inborn error of metabolism - targeted testing not possible v0.4 XPNPEP3 Ellen McDonagh gene: XPNPEP3 was added
gene: XPNPEP3 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: XPNPEP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XPNPEP3 were set to PMID: 20179356
Phenotypes for gene: XPNPEP3 were set to nephronophthisis-like nephropathy
Likely inborn error of metabolism - targeted testing not possible v0.4 VPS33B Ellen McDonagh gene: VPS33B was added
gene: VPS33B was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: VPS33B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS33B were set to 27604308
Phenotypes for gene: VPS33B were set to Inherited bleeding disorders; Unexplained kidney failure in young people; CAKUT; ARC Syndrome (Other metabolic disorders); Arthrogryposis
Likely inborn error of metabolism - targeted testing not possible v0.4 VIPAS39 Ellen McDonagh gene: VIPAS39 was added
gene: VIPAS39 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: VIPAS39 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VIPAS39 were set to 27604308
Phenotypes for gene: VIPAS39 were set to Inherited bleeding disorders; ARC Syndrome (Other metabolic disorders); Arthrogryposis
Likely inborn error of metabolism - targeted testing not possible v0.4 VARS2 Ellen McDonagh Added phenotypes Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 20, 615917 for gene: VARS2
Likely inborn error of metabolism - targeted testing not possible v0.4 VARS2 Ellen McDonagh gene: VARS2 was added
gene: VARS2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: VARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VARS2 were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 20, 615917
Likely inborn error of metabolism - targeted testing not possible v0.4 UROS Ellen McDonagh gene: UROS was added
gene: UROS was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: UROS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UROS were set to 27604308
Phenotypes for gene: UROS were set to Congenital erythropoietic porphyria (Porphyrias with erosive photodermatosis); Porphyria, congenital erythropoietic 263700
Likely inborn error of metabolism - targeted testing not possible v0.4 UROC1 Ellen McDonagh gene: UROC1 was added
gene: UROC1 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: UROC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UROC1 were set to 27604308
Phenotypes for gene: UROC1 were set to Intellectual disability; Urocanase deficiency (Disorders of histidine, tryptophan or lysine metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 TUSC3 Ellen McDonagh Added phenotypes TUSC3-CDG (Disorders of protein N-glycosylation); Mental retardation, autosomal recessive 7 for gene: TUSC3
Publications for gene TUSC3 were changed from 18452889; 18455129; 27148795; 26864433 to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 TUSC3 Ellen McDonagh gene: TUSC3 was added
gene: TUSC3 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: TUSC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TUSC3 were set to 18452889; 18455129; 27148795; 26864433
Phenotypes for gene: TUSC3 were set to Mental retardation, autosomal recessive 7
Likely inborn error of metabolism - targeted testing not possible v0.4 TUFM Ellen McDonagh Added phenotypes Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Combined oxidative phosphorylation deficiency 4 610678 for gene: TUFM
Publications for gene TUFM were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 TUFM Ellen McDonagh gene: TUFM was added
gene: TUFM was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: TUFM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TUFM were set to Combined oxidative phosphorylation deficiency 4, 610678; Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 TSFM Ellen McDonagh Added phenotypes Combined oxidative phosphorylation deficiency 3 610505; Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) for gene: TSFM
Publications for gene TSFM were changed from 27604308; 25037205; 17033963 to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 TRPM6 Ellen McDonagh gene: TRPM6 was added
gene: TRPM6 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: TRPM6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRPM6 were set to 27604308; 23942199; 12032570
Phenotypes for gene: TRPM6 were set to Hypomagnesemia 1, intestinal 602014; Hypomagnesaemia type 1, intestinal (Disorder of magnesium metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 TRNT1 Ellen McDonagh Added phenotypes congenital sideroblastic anemia with B cell immunodeficiency, fevers, and developmental delay (SIFD); retinitis pigmentosa with erythrocytic microcytosis for gene: TRNT1
Publications for gene TRNT1 were changed from PMID: 26494905; PMID: 25652405 to 25652405; 26494905
Likely inborn error of metabolism - targeted testing not possible v0.4 TRNT1 Ellen McDonagh gene: TRNT1 was added
gene: TRNT1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: TRNT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRNT1 were set to PMID: 26494905; PMID: 25652405
Phenotypes for gene: TRNT1 were set to congenital sideroblastic anemia with B cell immunodeficiency, fevers, and developmental delay (SIFD); retinitis pigmentosa with erythrocytic microcytosis
Likely inborn error of metabolism - targeted testing not possible v0.4 TRMU Ellen McDonagh Added phenotypes {Deafness, mitochondrial, modifier of}, 580000; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Liver failure, transient infantile, 613070 for gene: TRMU
Publications for gene TRMU were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 TRMU Ellen McDonagh gene: TRMU was added
gene: TRMU was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: TRMU was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRMU were set to {Deafness, mitochondrial, modifier of}, 580000; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Liver failure, transient infantile, 613070
Likely inborn error of metabolism - targeted testing not possible v0.4 TPP1 Ellen McDonagh gene: TPP1 was added
gene: TPP1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: TPP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TPP1 were set to 27604308
Phenotypes for gene: TPP1 were set to Intellectual disability; Ceroid lipofuscinosis, neuronal, 2; CLN2, Jansky-Bielschowsky disease (Ceroid lipfuscinoses, neuronal); Hereditary ataxia
Likely inborn error of metabolism - targeted testing not possible v0.4 TH Ellen McDonagh gene: TH was added
gene: TH was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: TH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TH were set to 27604308
Phenotypes for gene: TH were set to Intellectual disability; Early onset dystonia; Tyrosine hydroxylase deficiency (Disorders of neurotransmitter metabolism, biogenic amines); Parkinson Disease and Complex Parkinsonism
Likely inborn error of metabolism - targeted testing not possible v0.4 TFR2 Ellen McDonagh gene: TFR2 was added
gene: TFR2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: TFR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TFR2 were set to 27604308
Phenotypes for gene: TFR2 were set to Hemochromatosis, type 3 604250; Hereditary haemochromatosis Type 3 (Disorder of iron metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 TCN2 Ellen McDonagh gene: TCN2 was added
gene: TCN2 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: TCN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TCN2 were set to 27604308
Phenotypes for gene: TCN2 were set to Congenital neutropaenia; Intellectual disability; A- or hypo-gammaglobulinaemia; Agranulocytosis; Combined B and T cell defect; SCID; Transcobalamin II deficiency (Disorders of cobalamin absorption, transport and metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 TAT Ellen McDonagh gene: TAT was added
gene: TAT was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: TAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAT were set to 27604308
Phenotypes for gene: TAT were set to Intellectual disability; Tyrosinaemia type II (Disorders of phenylalanine or tyrosine metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 TANGO2 Ellen McDonagh gene: TANGO2 was added
gene: TANGO2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: TANGO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TANGO2 were set to 26805782; 26805781
Phenotypes for gene: TANGO2 were set to Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration 616878
Likely inborn error of metabolism - targeted testing not possible v0.4 TACO1 Ellen McDonagh Added phenotypes Mitochondrial Respiratory Chain Complex IV Deficiency; Mitochondrial Diseases; ?Mitochondrial complex IV deficiency, 220110; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Isolated complex IV deficiency for gene: TACO1
Likely inborn error of metabolism - targeted testing not possible v0.4 TACO1 Ellen McDonagh gene: TACO1 was added
gene: TACO1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: TACO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TACO1 were set to 27604308
Phenotypes for gene: TACO1 were set to Mitochondrial Diseases; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); ?Mitochondrial complex IV deficiency, 220110; Isolated complex IV deficiency; Mitochondrial Respiratory Chain Complex IV Deficiency; Complex IV (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors)
Likely inborn error of metabolism - targeted testing not possible v0.4 ST3GAL5 Ellen McDonagh Added phenotypes Lactosylceramide alpha-2,3-sialyltransferase deficiency (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation); Salt and pepper developmental regression syndrome 609056 for gene: ST3GAL5
Publications for gene ST3GAL5 were changed from 27604308 to 24026681; 15502825
Likely inborn error of metabolism - targeted testing not possible v0.4 ST3GAL5 Ellen McDonagh gene: ST3GAL5 was added
gene: ST3GAL5 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: ST3GAL5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ST3GAL5 were set to 27604308
Phenotypes for gene: ST3GAL5 were set to Lactosylceramide alpha-2,3-sialyltransferase deficiency (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation); Salt and pepper developmental regression syndrome 609056; GM3 synthase deficiency (Disorders of complex lipid synthesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC7A7 Ellen McDonagh gene: SLC7A7 was added
gene: SLC7A7 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: SLC7A7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC7A7 were set to 27604308
Phenotypes for gene: SLC7A7 were set to Lysinuric protein intolerance (Disorders of amino acid transport); Lysinuric protein intolerance 222700
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC39A8 Ellen McDonagh gene: SLC39A8 was added
gene: SLC39A8 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: SLC39A8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC39A8 were set to 27604308
Phenotypes for gene: SLC39A8 were set to Congenital disorder of glycosylation, type IIn 616721; Hypomagnesaemia with cerebellar atrophy, hypotonia, strabismus, developmental delay, short stature, mild skeletal dysplasia, and connective tissue abnormalities (Disorder of magnesium metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC35D1 Ellen McDonagh Added phenotypes 9.2.3. O-xylosyl/N-acetylgalactosaminylglycan synthesis deficiencies (Disorders of protein O-glycosylation) for gene: SLC35D1
Publications for gene SLC35D1 were changed from 27604308 to 19508970; 17952091
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC35D1 Ellen McDonagh gene: SLC35D1 was added
gene: SLC35D1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: SLC35D1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC35D1 were set to 27604308
Phenotypes for gene: SLC35D1 were set to 9.2.3. O-xylosyl/N-acetylgalactosaminylglycan synthesis deficiencies (Disorders of protein O-glycosylation)
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC35A3 Ellen McDonagh gene: SLC35A3 was added
gene: SLC35A3 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: SLC35A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC35A3 were set to 24031089
Phenotypes for gene: SLC35A3 were set to Arthrogryposis, mental retardation, and seizures
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC35A1 Ellen McDonagh Added phenotypes Congenital disorder of glycosylation, type Iif, 603585; CMP-sialic acid transporter deficiency (Disorders of multiple glycosylation and other glycosylation pathways) for gene: SLC35A1
Publications for gene SLC35A1 were changed from 23873973; 15576474 to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC35A1 Ellen McDonagh gene: SLC35A1 was added
gene: SLC35A1 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: SLC35A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC35A1 were set to 23873973; 15576474
Phenotypes for gene: SLC35A1 were set to Congenital disorder of glycosylation, type IIf 603585; CMP-sialic acid transporter deficiency (Disorders of multiple glycosylation and other glycosylation pathways)
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC30A10 Ellen McDonagh gene: SLC30A10 was added
gene: SLC30A10 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: SLC30A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC30A10 were set to 27604308
Phenotypes for gene: SLC30A10 were set to Parkinson Disease and Complex Parkinsonism; Early onset dystonia; Hypermanganesemia with dystonia 1; Hypermanganesemia with dystonia, polycythemia, and cirrhosis (Disorder of magnesium metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC27A5 Ellen McDonagh gene: SLC27A5 was added
gene: SLC27A5 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: SLC27A5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC27A5 were set to 27604308
Phenotypes for gene: SLC27A5 were set to Bile acid CoA ligase deficiency (Disorders of bile acid biosynthesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC25A38 Ellen McDonagh Added phenotypes severe, non-syndromic, microcytic/hypochromic sideroblastic anemia; nonsyndromic autosomal recessive congenital sideroblastic anemia; congenital sideroblastic anemias for gene: SLC25A38
Publications for gene SLC25A38 were changed from 27604308 to PMID: 26821380 (potential novel treatment using glycine and folate).; PMID: 19731322 (12 probands with mutations in this gene); PMID: 25985931 (mutations detected in 3 patients in this gene); PMID: 21393332 (11 patients); PMID: 19412178
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC25A38 Ellen McDonagh gene: SLC25A38 was added
gene: SLC25A38 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: SLC25A38 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A38 were set to 27604308
Phenotypes for gene: SLC25A38 were set to severe, non-syndromic, microcytic/hypochromic sideroblastic anemia; nonsyndromic autosomal recessive congenital sideroblastic anemia; Disorders of mitochondrial solute import (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); congenital sideroblastic anemias
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC25A26 Ellen McDonagh Added phenotypes Combined oxidative phosphorylation deficiency 28; intra-mitochondrial methylation deficiency.; Intra-mitochondrial Methylation Deficiency leading to Clinical findings ranging from neonatal mortality resulting from respiratory insufficiency and hydrops to childhood acute episodes of cardiopulmonary failure and slowly progressive muscle weakness for gene: SLC25A26
Publications for gene SLC25A26 were changed from PMID: 26522469 to 26522469
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC25A26 Ellen McDonagh gene: SLC25A26 was added
gene: SLC25A26 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: SLC25A26 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A26 were set to PMID: 26522469
Phenotypes for gene: SLC25A26 were set to Combined oxidative phosphorylation deficiency 28; intra-mitochondrial methylation deficiency.; Intra-mitochondrial Methylation Deficiency leading to Clinical findings ranging from neonatal mortality resulting from respiratory insufficiency and hydrops to childhood acute episodes of cardiopulmonary failure and slowly progressive muscle weakness
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC25A19 Ellen McDonagh Added phenotypes Microcephaly, Amish type, 607196; Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type), 613710; Microcephaly, Amish type (Disorders of thiamine metabolism) for gene: SLC25A19
Publications for gene SLC25A19 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC25A19 Ellen McDonagh gene: SLC25A19 was added
gene: SLC25A19 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: SLC25A19 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC25A19 were set to Microcephaly, Amish type, 607196; Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type), 613710
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC19A3 Ellen McDonagh Added phenotypes Biotin-responsive basal ganglia disease (Disorders of thiamine metabolism); Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2),607483 for gene: SLC19A3
Publications for gene SLC19A3 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC19A3 Ellen McDonagh gene: SLC19A3 was added
gene: SLC19A3 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: SLC19A3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC19A3 were set to Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2),607483
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC19A2 Ellen McDonagh Added phenotypes Thiamine-responsive megaloblastic anemia syndrome, 249270; Thiamine-responsive megaloblastic anemia syndrome (Disorders of thiamine metabolism) for gene: SLC19A2
Publications for gene SLC19A2 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC19A2 Ellen McDonagh gene: SLC19A2 was added
gene: SLC19A2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: SLC19A2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC19A2 were set to Thiamine-responsive megaloblastic anemia syndrome, 249270
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC18A2 Ellen McDonagh gene: SLC18A2 was added
gene: SLC18A2 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: SLC18A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC18A2 were set to 27604308; 26497564; 23363473
Phenotypes for gene: SLC18A2 were set to Brain Dopamine Serotonin Vesicular Transport Disease (Other disorders of neurotransmitter metabolism); Brain Dopamine Serotonin Vesicular Transport Disease (Other disorders of neurotransmitter metabolism) (NO phenotype number in OMIM)
Likely inborn error of metabolism - targeted testing not possible v0.4 SLC12A3 Ellen McDonagh gene: SLC12A3 was added
gene: SLC12A3 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: SLC12A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC12A3 were set to 27604308
Phenotypes for gene: SLC12A3 were set to Gitelman syndrome (Disorder of magnesium metabolism); Renal tubular acidosis
Likely inborn error of metabolism - targeted testing not possible v0.4 SI Ellen McDonagh gene: SI was added
gene: SI was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: SI was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SI were set to 27604308; 14724820; 8648527; 16329100
Phenotypes for gene: SI were set to CONGENITAL SUCRASE-ISOMALTASE DEFICIENCY 222900; Disaccharide intolerance 1 (Other carbohydrate disorders)
Likely inborn error of metabolism - targeted testing not possible v0.4 SGSH Ellen McDonagh gene: SGSH was added
gene: SGSH was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: SGSH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SGSH were set to 27604308
Phenotypes for gene: SGSH were set to Mucopolysaccharidosis Type III; Mucopolysaccharidosis, Type III; Mucopolysaccharidosis Type IIIA; MPS IIIA, Sanfilippo A disease (Mucopolysaccharidoses); MUCOPOLYSACCHARIDOSIS TYPE 3A
Likely inborn error of metabolism - targeted testing not possible v0.4 SERAC1 Ellen McDonagh Added phenotypes Disorders of mitochondrial membrane lipids (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Methylglutaconic aciduria with deafness, encephalopathy and Leigh-like syndrome (MEGDEL) (Organic acidurias); 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, 614739 for gene: SERAC1
Publications for gene SERAC1 were changed from 29205472 to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 SERAC1 Ellen McDonagh gene: SERAC1 was added
gene: SERAC1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: SERAC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SERAC1 were set to 29205472
Phenotypes for gene: SERAC1 were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, 614739
Likely inborn error of metabolism - targeted testing not possible v0.4 SC5D Ellen McDonagh gene: SC5D was added
gene: SC5D was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: SC5D was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SC5D were set to 27604308
Phenotypes for gene: SC5D were set to Lathosterolosis (Disorders of sterol biosynthesis); Intellectual disability; Cataracts
Likely inborn error of metabolism - targeted testing not possible v0.4 SARS2 Ellen McDonagh Added phenotypes Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis, 613845; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) for gene: SARS2
Publications for gene SARS2 were changed from PMID: 21255763; 24034276 to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 SARS2 Ellen McDonagh gene: SARS2 was added
gene: SARS2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: SARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SARS2 were set to PMID: 21255763; 24034276
Phenotypes for gene: SARS2 were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis, 613845
Likely inborn error of metabolism - targeted testing not possible v0.4 SARDH Ellen McDonagh gene: SARDH was added
gene: SARDH was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: SARDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SARDH were set to 27604308
Phenotypes for gene: SARDH were set to [Sarcosinemia] 268900; Sarcosinaemia (Disorders of serine, glycine or glycerate metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 SACS Ellen McDonagh Added phenotypes Spastic ataxia, Charlevoix-Saguenay type; Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) for gene: SACS
Publications for gene SACS were changed from PMID: 14718708 (two family members); PMID: 10655055 (17 families with 24 patients); PMID: 15985586 (two siblings); PMID: 14718706 (two sisters); PMID: 12873855 (18 patients from 4 families); PMID: 16606928 (case study) to 12873855 (18 patients from 4 families); 15985586 (two siblings); 14718706 (two sisters); 16606928 (case study); 10655055 (17 families with 24 patients); 14718708 (two family members)
Likely inborn error of metabolism - targeted testing not possible v0.4 SACS Ellen McDonagh gene: SACS was added
gene: SACS was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: SACS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SACS were set to PMID: 14718708 (two family members); PMID: 10655055 (17 families with 24 patients); PMID: 15985586 (two siblings); PMID: 14718706 (two sisters); PMID: 12873855 (18 patients from 4 families); PMID: 16606928 (case study)
Phenotypes for gene: SACS were set to Spastic ataxia, Charlevoix-Saguenay type; Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS)
Likely inborn error of metabolism - targeted testing not possible v0.4 ROBO3 Ellen McDonagh gene: ROBO3 was added
gene: ROBO3 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: ROBO3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ROBO3 were set to 16525029; 15105459
Phenotypes for gene: ROBO3 were set to Gaze palsy, familial horizontal, with progressive scoliosis, 1, 607313
Likely inborn error of metabolism - targeted testing not possible v0.4 RNASEH1 Ellen McDonagh Added phenotypes Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 2 for gene: RNASEH1
Likely inborn error of metabolism - targeted testing not possible v0.4 RNASEH1 Ellen McDonagh gene: RNASEH1 was added
gene: RNASEH1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: RNASEH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEH1 were set to Reyes et al., 2005, Am. J. Hum. Genet., 97, 186-193.
Phenotypes for gene: RNASEH1 were set to Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 2
Likely inborn error of metabolism - targeted testing not possible v0.4 RMND1 Ellen McDonagh Added phenotypes Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Combined oxidative phosphorylation deficiency 11, 614922; Encephalopathy associated with multiple oxidative phosphorylation complex deficiencies and a mitochondrial translation defect for gene: RMND1
Publications for gene RMND1 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 RMND1 Ellen McDonagh gene: RMND1 was added
gene: RMND1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: RMND1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RMND1 were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 11, 614922; Encephalopathy associated with multiple oxidative phosphorylation complex deficiencies and a mitochondrial translation defect
Likely inborn error of metabolism - targeted testing not possible v0.4 RARS2 Ellen McDonagh Added phenotypes Pontocerebellar hypoplasia, type 6, 611523; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) for gene: RARS2
Publications for gene RARS2 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 RARS2 Ellen McDonagh gene: RARS2 was added
gene: RARS2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: RARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RARS2 were set to Pontocerebellar hypoplasia, type 6, 611523; Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 PYCR1 Ellen McDonagh Added phenotypes Cutis laxa, autosomal recessive, type IIIB, 614438; Cutis laxa, autosomal recessive, type IIB, 612940 for gene: PYCR1
Likely inborn error of metabolism - targeted testing not possible v0.4 PYCR1 Ellen McDonagh gene: PYCR1 was added
gene: PYCR1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PYCR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PYCR1 were set to 27604308
Phenotypes for gene: PYCR1 were set to Cutis laxa, autosomal recessive, type IIIB, 614438; Cutis laxa, autosomal recessive, type IIb/IIIb (Disorders of ornithine or proline metabolism); Cutis laxa, autosomal recessive, type IIB, 612940
Likely inborn error of metabolism - targeted testing not possible v0.4 PUS1 Ellen McDonagh Added phenotypes Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Mitochondrial myopathy and sideroblastic anemia 1, 600462 for gene: PUS1
Likely inborn error of metabolism - targeted testing not possible v0.4 PUS1 Ellen McDonagh gene: PUS1 was added
gene: PUS1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PUS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PUS1 were set to 27604308
Phenotypes for gene: PUS1 were set to Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only))
Likely inborn error of metabolism - targeted testing not possible v0.4 PSPH Ellen McDonagh gene: PSPH was added
gene: PSPH was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: PSPH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSPH were set to 27604308; 24816252
Phenotypes for gene: PSPH were set to Intellectual disability; Phosphoserine phosphatase deficiency (Disorders of serine, glycine or glycerate metabolism); Unexplained skeletal dysplasia
Likely inborn error of metabolism - targeted testing not possible v0.4 PSAT1 Ellen McDonagh gene: PSAT1 was added
gene: PSAT1 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: PSAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSAT1 were set to 27604308
Phenotypes for gene: PSAT1 were set to Phosphoserine aminotransferase deficiency (Disorders of serine, glycine or glycerate metabolism); Unexplained skeletal dysplasia
Likely inborn error of metabolism - targeted testing not possible v0.4 PSAP Ellen McDonagh gene: PSAP was added
gene: PSAP was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PSAP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSAP were set to 27604308
Phenotypes for gene: PSAP were set to Atypical Gaucher disease; Metachromatic leukodystrophy due to SAP-b deficiency, 249900; Combined SAP deficiency; Combined SAP deficiency, 611721; Prosaposin deficiency (Sphingolipidoses); Atypical Krabbe disease; Gaucher disease, atypical, 610539; Krabbe disease, atypical, 611722
Likely inborn error of metabolism - targeted testing not possible v0.4 PPT1 Ellen McDonagh gene: PPT1 was added
gene: PPT1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PPT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPT1 were set to 27604308
Phenotypes for gene: PPT1 were set to Ceroid lipofuscinosis, neuronal, 1
Likely inborn error of metabolism - targeted testing not possible v0.4 POR Ellen McDonagh gene: POR was added
gene: POR was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: POR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POR were set to 27604308
Phenotypes for gene: POR were set to Antley-Bixler syndrome with disordered steroidogenesis; Unexplained skeletal dysplasia; Disorders of sex development; Craniosynostosis syndromes phenotypes
Likely inborn error of metabolism - targeted testing not possible v0.4 POMT2 Ellen McDonagh Added phenotypes Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 2 613158; Protein-O-mannosyltransferase 2 deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies); Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 613150; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 2 613156 for gene: POMT2
Publications for gene POMT2 were changed from 27604308 to 27421908
Likely inborn error of metabolism - targeted testing not possible v0.4 POMT2 Ellen McDonagh gene: POMT2 was added
gene: POMT2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: POMT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POMT2 were set to 27604308
Phenotypes for gene: POMT2 were set to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 2 613158; Protein-O-mannosyltransferase 2 deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies); Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 613150; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 2 613156
Likely inborn error of metabolism - targeted testing not possible v0.4 POMT1 Ellen McDonagh Added phenotypes Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1 613155; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 609308; Protein-O-mannosyltransferase 1 deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies); Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 236670 for gene: POMT1
Publications for gene POMT1 were changed from 27421908 to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 POMT1 Ellen McDonagh gene: POMT1 was added
gene: POMT1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: POMT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POMT1 were set to 27421908
Phenotypes for gene: POMT1 were set to Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1 613155; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 1 609308; Protein-O-mannosyltransferase 1 deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies); Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 236670
Likely inborn error of metabolism - targeted testing not possible v0.4 POMGNT1 Ellen McDonagh Added phenotypes Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3 253280; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C 3 613157; Protein-O-mannose beta-1,2-N-acetyglucosaminyltransferase deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies); Retinitis pigmentosa 76 617123 for gene: POMGNT1
Publications for gene POMGNT1 were changed from 27604308 to 27421908
Likely inborn error of metabolism - targeted testing not possible v0.4 POMGNT1 Ellen McDonagh gene: POMGNT1 was added
gene: POMGNT1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: POMGNT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POMGNT1 were set to 27604308
Phenotypes for gene: POMGNT1 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3 253280; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C 3 613157; Protein-O-mannose beta-1,2-N-acetyglucosaminyltransferase deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies); Retinitis pigmentosa 76 617123
Likely inborn error of metabolism - targeted testing not possible v0.4 PNPT1 Ellen McDonagh Added phenotypes Deafness, autosomal recessive 70, 614934; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 13, 614932; respiratory chain disorder; hearing loss; Disorders of mitochondrial protein import (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) for gene: PNPT1
Publications for gene PNPT1 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 PNPT1 Ellen McDonagh gene: PNPT1 was added
gene: PNPT1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PNPT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PNPT1 were set to respiratory chain disorder; Deafness, autosomal recessive 70, 614934; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 13, 614932; hearing loss
Likely inborn error of metabolism - targeted testing not possible v0.4 PNP Ellen McDonagh gene: PNP was added
gene: PNP was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: PNP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNP were set to 27604308
Phenotypes for gene: PNP were set to SCID; Purine nucleoside phosphorylase deficiency (Disorders of purine metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 PMPCA Ellen McDonagh Added phenotypes slowly progressive cerebellar ataxia; non-progressive cerebellar ataxia for gene: PMPCA
Publications for gene PMPCA were changed from PMID: 25808372; PMID: 26657514 to 26657514; 25808372
Likely inborn error of metabolism - targeted testing not possible v0.4 PMPCA Ellen McDonagh gene: PMPCA was added
gene: PMPCA was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PMPCA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PMPCA were set to PMID: 25808372; PMID: 26657514
Phenotypes for gene: PMPCA were set to slowly progressive cerebellar ataxia; non-progressive cerebellar ataxia
Likely inborn error of metabolism - targeted testing not possible v0.4 PITRM1 Ellen McDonagh gene: PITRM1 was added
gene: PITRM1 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: PITRM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PITRM1 were set to PMID: 26697887
Phenotypes for gene: PITRM1 were set to mental retardation, spinocerebellar ataxia, cognitive decline and psychosis
Likely inborn error of metabolism - targeted testing not possible v0.4 PIGW Ellen McDonagh gene: PIGW was added
gene: PIGW was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: PIGW was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGW were set to 24367057
Phenotypes for gene: PIGW were set to ?Hyperphosphatasia with mental retardation syndrome 5
Likely inborn error of metabolism - targeted testing not possible v0.4 PIGV Ellen McDonagh Added phenotypes Hyperphosphatasia with mental retardation syndrome 1 239300; (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation) for gene: PIGV
Publications for gene PIGV were changed from 27604308 to 20802478; 24129430
Likely inborn error of metabolism - targeted testing not possible v0.4 PIGV Ellen McDonagh gene: PIGV was added
gene: PIGV was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PIGV was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGV were set to 27604308
Phenotypes for gene: PIGV were set to Hyperphosphatasia (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation); Hyperphosphatasia with mental retardation syndrome 1 239300; (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation)
Likely inborn error of metabolism - targeted testing not possible v0.4 PIGO Ellen McDonagh Added phenotypes (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation); Hyperphosphatasia (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation); Hyperphosphatasia with mental retardation syndrome 2 614749 for gene: PIGO
Publications for gene PIGO were changed from 22683086; 27177984; 24129430 to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 PIGO Ellen McDonagh gene: PIGO was added
gene: PIGO was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PIGO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGO were set to 22683086; 27177984; 24129430
Phenotypes for gene: PIGO were set to (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation); Hyperphosphatasia with mental retardation syndrome 2 614749
Likely inborn error of metabolism - targeted testing not possible v0.4 PIGN Ellen McDonagh gene: PIGN was added
gene: PIGN was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PIGN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGN were set to 27604308
Phenotypes for gene: PIGN were set to PIGN-CDG (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation); Multiple congenital anomalies-hypotonia-seizures syndrome 1
Likely inborn error of metabolism - targeted testing not possible v0.4 PIGM Ellen McDonagh Added phenotypes Phosphatidylinositolglycan, class M deficiency (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation); Glycosylphosphatidylinositol deficiency 610293 for gene: PIGM
Likely inborn error of metabolism - targeted testing not possible v0.4 PIGM Ellen McDonagh gene: PIGM was added
gene: PIGM was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: PIGM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGM were set to 27604308; 16767100; 25293775
Phenotypes for gene: PIGM were set to Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation; Glycosylphosphatidylinositol deficiency, 610293; Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency
Likely inborn error of metabolism - targeted testing not possible v0.4 PIGL Ellen McDonagh Added phenotypes PIGL-CDG (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation); CHIME syndrome 280000 for gene: PIGL
Publications for gene PIGL were changed from 27604308 to 22444671
Likely inborn error of metabolism - targeted testing not possible v0.4 PIGL Ellen McDonagh gene: PIGL was added
gene: PIGL was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PIGL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGL were set to 27604308
Phenotypes for gene: PIGL were set to PIGL-CDG (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation); CHIME syndrome 280000
Likely inborn error of metabolism - targeted testing not possible v0.4 PHYKPL Ellen McDonagh gene: PHYKPL was added
gene: PHYKPL was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: PHYKPL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PHYKPL were set to 27604308
Phenotypes for gene: PHYKPL were set to Hydroxylysinuria (Disorders of histidine, tryptophan or lysine metabolism); [?Phosphohydroxylysinuria] 615011
Likely inborn error of metabolism - targeted testing not possible v0.4 PHKG2 Ellen McDonagh gene: PHKG2 was added
gene: PHKG2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PHKG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PHKG2 were set to 27604308
Phenotypes for gene: PHKG2 were set to hepatomegaly and variable myopathy; Glycogen Storage Disorders- Liver; Glycogen Storage Disease; Glycogen storage disease IXc, 613027; Glycogen storage disease type IX Hepatic phosphorylase kinase deficiency with cirrhosis (Glycogen storage disorders); Cirrhosis due to liver phosphorylase kinase deficiency
Likely inborn error of metabolism - targeted testing not possible v0.4 PHGDH Ellen McDonagh gene: PHGDH was added
gene: PHGDH was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: PHGDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PHGDH were set to 27604308; 24816252
Phenotypes for gene: PHGDH were set to Phosphoglycerate dehydrogenase deficiency (Disorders of serine, glycine or glycerate metabolism); Unexplained skeletal dysplasia; Intellectual disability
Likely inborn error of metabolism - targeted testing not possible v0.4 PGAP3 Ellen McDonagh Added phenotypes Hyperphosphatasia with mental retardation syndrome 4 for gene: PGAP3
Likely inborn error of metabolism - targeted testing not possible v0.4 PGAP3 Ellen McDonagh gene: PGAP3 was added
gene: PGAP3 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PGAP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PGAP3 were set to 24439110
Phenotypes for gene: PGAP3 were set to Hyperphosphatasia with mental retardation syndrome 4
Likely inborn error of metabolism - targeted testing not possible v0.4 PGAP2 Ellen McDonagh Added phenotypes Hyperphosphatasia with mental retardation syndrome 3 614207; PGAP2-CDG (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation) for gene: PGAP2
Publications for gene PGAP2 were changed from 23561846; 23561847 to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 PGAP2 Ellen McDonagh gene: PGAP2 was added
gene: PGAP2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PGAP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PGAP2 were set to 23561846; 23561847
Phenotypes for gene: PGAP2 were set to Hyperphosphatasia with mental retardation syndrome 3 614207; PGAP2-CDG (Disorders of glycosphingolipid and glycosylphosphatidylinositol anchor glycosylation)
Likely inborn error of metabolism - targeted testing not possible v0.4 PGAM2 Ellen McDonagh gene: PGAM2 was added
gene: PGAM2 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: PGAM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PGAM2 were set to 27604308
Phenotypes for gene: PGAM2 were set to Glycogen storage disease type X (Glycogen storage disorders); Rhabdomyolysis and metabolic muscle disorders
Likely inborn error of metabolism - targeted testing not possible v0.4 PEX7 Ellen McDonagh gene: PEX7 was added
gene: PEX7 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PEX7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX7 were set to 27604308
Phenotypes for gene: PEX7 were set to Peroxisome biogenesis disorder 9B 614879; Rhizomelic chondrodysplasia punctata, type 1; Rhizomelic chondrodysplasia punctata type 1 (Peroxisomal disorders)
Likely inborn error of metabolism - targeted testing not possible v0.4 PEX6 Ellen McDonagh gene: PEX6 was added
gene: PEX6 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PEX6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX6 were set to 27604308
Phenotypes for gene: PEX6 were set to Disorders of peroxisome biogenesis; Peroxisome biogenesis disorder 4B 614863; Peroxisome biogenesis disorder 4A (Zellweger) 614862
Likely inborn error of metabolism - targeted testing not possible v0.4 PEX5 Ellen McDonagh gene: PEX5 was added
gene: PEX5 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PEX5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX5 were set to 27604308
Phenotypes for gene: PEX5 were set to Disorders of peroxisome biogenesis; Peroxisome biogenesis disorder 2A (Zellweger)
Likely inborn error of metabolism - targeted testing not possible v0.4 PEX3 Ellen McDonagh gene: PEX3 was added
gene: PEX3 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PEX3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX3 were set to 27604308
Phenotypes for gene: PEX3 were set to Disorders of peroxisome biogenesis; Peroxisome biogenesis disorder 10A (Zellweger) 614882
Likely inborn error of metabolism - targeted testing not possible v0.4 PEX26 Ellen McDonagh gene: PEX26 was added
gene: PEX26 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PEX26 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX26 were set to 27604308
Phenotypes for gene: PEX26 were set to Disorders of peroxisome biogenesis; Peroxisome biogenesis disorder 7A (Zellweger) 61487; Peroxisome biogenesis disorder 7B 614873
Likely inborn error of metabolism - targeted testing not possible v0.4 PEX2 Ellen McDonagh gene: PEX2 was added
gene: PEX2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PEX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX2 were set to 27604308
Phenotypes for gene: PEX2 were set to Disorders of peroxisome biogenesis; Peroxisome biogenesis disorder 5A (Zellweger), 614866; Peroxisome biogenesis disorder 5B, 614867
Likely inborn error of metabolism - targeted testing not possible v0.4 PEX19 Ellen McDonagh gene: PEX19 was added
gene: PEX19 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PEX19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX19 were set to 27604308
Phenotypes for gene: PEX19 were set to Disorders of peroxisome biogenesis; Peroxisome biogenesis disorder 12A (Zellweger)
Likely inborn error of metabolism - targeted testing not possible v0.4 PEX16 Ellen McDonagh gene: PEX16 was added
gene: PEX16 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PEX16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX16 were set to 27604308
Phenotypes for gene: PEX16 were set to Disorders of peroxisome biogenesis; Peroxisome Biogenesis Disorders, Zellweger Syndrome Spectrum; Peroxisome biogenesis disorder 8A, (Zellweger), 614876; Peroxisomal biogenesis disorders; Zellweger Syndrome
Likely inborn error of metabolism - targeted testing not possible v0.4 PEX14 Ellen McDonagh gene: PEX14 was added
gene: PEX14 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PEX14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX14 were set to 27604308
Phenotypes for gene: PEX14 were set to Disorders of peroxisome biogenesis; Peroxisome biogenesis disorder 13A (Zellweger)
Likely inborn error of metabolism - targeted testing not possible v0.4 PEX13 Ellen McDonagh gene: PEX13 was added
gene: PEX13 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PEX13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX13 were set to 27604308
Phenotypes for gene: PEX13 were set to Disorders of peroxisome biogenesis; Peroxisome biogenesis disorder 11A (Zellweger)
Likely inborn error of metabolism - targeted testing not possible v0.4 PEX12 Ellen McDonagh gene: PEX12 was added
gene: PEX12 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PEX12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX12 were set to 27604308
Phenotypes for gene: PEX12 were set to Disorders of peroxisome biogenesis; Peroxisome biogenesis disorder 3A (Zellweger), 614859; Peroxisome biogenesis disorder 3B
Likely inborn error of metabolism - targeted testing not possible v0.4 PEX11B Ellen McDonagh gene: PEX11B was added
gene: PEX11B was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PEX11B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PEX11B were set to Peroxisome biogenesis disorder 14B
Likely inborn error of metabolism - targeted testing not possible v0.4 PEX10 Ellen McDonagh gene: PEX10 was added
gene: PEX10 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PEX10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX10 were set to 27604308
Phenotypes for gene: PEX10 were set to Disorders of peroxisome biogenesis; Peroxisome biogenesis disorder 6A (Zellweger) 614870; Peroxisome biogenesis disorder 6B 614871
Likely inborn error of metabolism - targeted testing not possible v0.4 PEX1 Ellen McDonagh gene: PEX1 was added
gene: PEX1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PEX1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PEX1 were set to 27604308
Phenotypes for gene: PEX1 were set to Disorders of peroxisome biogenesis; Peroxisome biogenesis disorder 1B (NALD/IRD) 601539; Peroxisome biogenesis disorder 1A (Zellweger) 214100
Likely inborn error of metabolism - targeted testing not possible v0.4 PDSS2 Ellen McDonagh Added phenotypes Coenzyme Q10 deficiency, primary, 3, 614652; Disorders of CoQ10 biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of ubiquinone metabolism and biosynthesis for gene: PDSS2
Publications for gene PDSS2 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 PDSS2 Ellen McDonagh gene: PDSS2 was added
gene: PDSS2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PDSS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PDSS2 were set to Coenzyme Q10 deficiency, primary, 3, 614652; Disorders of ubiquinone metabolism and biosynthesis
Likely inborn error of metabolism - targeted testing not possible v0.4 PDSS1 Ellen McDonagh Added phenotypes Coenzyme Q10 deficiency, primary, 2, 614651; Disorders of CoQ10 biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of ubiquinone metabolism and biosynthesis for gene: PDSS1
Publications for gene PDSS1 were changed from PMID: 22494076 (2012) - A girl with developmental delay, nephrotic syndrome, and failure to thrive was reported to be a compound heterozygote for two novel variants in PDSS1 (p.Arg221Term and p.Ser370Arg).; PMID: 17332895 (2007) - Report a homozygous nucleotide substitution modifying a conserved amino acid of the protein (D308E) in a consanguineous family with CoQ10 deficiency to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 PDSS1 Ellen McDonagh gene: PDSS1 was added
gene: PDSS1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PDSS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDSS1 were set to PMID: 22494076 (2012) - A girl with developmental delay, nephrotic syndrome, and failure to thrive was reported to be a compound heterozygote for two novel variants in PDSS1 (p.Arg221Term and p.Ser370Arg).; PMID: 17332895 (2007) - Report a homozygous nucleotide substitution modifying a conserved amino acid of the protein (D308E) in a consanguineous family with CoQ10 deficiency
Phenotypes for gene: PDSS1 were set to Coenzyme Q10 deficiency, primary, 2, 614651; Disorders of ubiquinone metabolism and biosynthesis
Likely inborn error of metabolism - targeted testing not possible v0.4 PCK1 Ellen McDonagh gene: PCK1 was added
gene: PCK1 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: PCK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCK1 were set to 27604308
Phenotypes for gene: PCK1 were set to Phosphoenolpyruvate carboxykinase deficiency (Disorders of gluconeogenesis); ?Phosphoenolpyruvate carboxykinase-1, cytosolic, deficiency; (PCK1 DEFICIENCY, Cytosolic phosphoenolpyruvate carboxykinase (PEPCK))
Likely inborn error of metabolism - targeted testing not possible v0.4 PCCB Ellen McDonagh gene: PCCB was added
gene: PCCB was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PCCB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCCB were set to 27604308
Phenotypes for gene: PCCB were set to as PCCA (metabolic encephalopathy with hyperammonaemia, hypotonia, recurrent episodes of ketoacidosis, liver impairment, psychomotor retardation, recurrent infections); Propionic acidemia; Propionicacidemia 606054; Propionicacidemia; Propionic aciduria (Organic acidurias)
Likely inborn error of metabolism - targeted testing not possible v0.4 PCCA Ellen McDonagh gene: PCCA was added
gene: PCCA was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PCCA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCCA were set to 27604308
Phenotypes for gene: PCCA were set to Propionicacidemia; Propionic acidemia; Propionicacidemia 606054; metabolic encephalopathy with hyperammonaemia, hypotonia, recurrent episodes of ketoacidosis, liver impairment, psychomotor retardation, recurrent infections; Propionic aciduria (Organic acidurias)
Likely inborn error of metabolism - targeted testing not possible v0.4 PC Ellen McDonagh gene: PC was added
gene: PC was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: PC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PC were set to 27604308
Phenotypes for gene: PC were set to Pyruvate carboxylase deficiency (Disorders of gluconeogenesis); lactic acidosis, hypotonia, encephalopathy; Pyruvate carboxylase deficiency 266150; Pyruvate carboxylase deficiency
Likely inborn error of metabolism - targeted testing not possible v0.4 PARS2 Ellen McDonagh gene: PARS2 was added
gene: PARS2 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: PARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PARS2 were set to PMID: 25629079 (single case)
Phenotypes for gene: PARS2 were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); No OMIM phenotype; Alpers syndrome.
Likely inborn error of metabolism - targeted testing not possible v0.4 OXCT1 Ellen McDonagh gene: OXCT1 was added
gene: OXCT1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: OXCT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: OXCT1 were set to 27604308
Phenotypes for gene: OXCT1 were set to Succinyl CoA:3-oxoacid CoA transferase deficiency; severe ketosis on fasting often ketotic in fed state no hepatomegaly; Succinyl-CoA:3-Oxoacid-CoA transferase (SCOT) deficiency (Disorders of ketone body metabolism); Succinyl CoA:3-oxoacid CoA transferase deficiency (Mitochondrial respiratory chain disorders (caused by nuclear variants only))
Likely inborn error of metabolism - targeted testing not possible v0.4 NUP62 Ellen McDonagh gene: NUP62 was added
gene: NUP62 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: NUP62 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP62 were set to 27604308
Phenotypes for gene: NUP62 were set to Infantile striatal necrosis (Other metabolic disorders); Striatonigral degeneration, infantile, 271930
Likely inborn error of metabolism - targeted testing not possible v0.4 NHLRC1 Ellen McDonagh gene: NHLRC1 was added
gene: NHLRC1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: NHLRC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NHLRC1 were set to 27604308
Phenotypes for gene: NHLRC1 were set to Epilepsy, progressive myoclonic 2B (Lafora)
Likely inborn error of metabolism - targeted testing not possible v0.4 NGLY1 Ellen McDonagh Added phenotypes OrphaNet: ORPHA404454; Alacrimia-choreoathetosis-liver dysfunction syndrome; OMIM:615273 for gene: NGLY1
Publications for gene NGLY1 were changed from to 25220016; 26350515; 25900930; 24651605; 25605922; 22581936; 25707956
Likely inborn error of metabolism - targeted testing not possible v0.4 NFU1 Ellen McDonagh Added phenotypes Multiple mitochondrial dysfunctions syndrome 1; Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) for gene: NFU1
Publications for gene NFU1 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 NEU1 Ellen McDonagh gene: NEU1 was added
gene: NEU1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: NEU1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NEU1 were set to 27604308
Phenotypes for gene: NEU1 were set to Sialidosis type II; Sialidosis, type I; Sialidosis (Oligosaccharidoses); Mucolipidosis, Type I; Sialidosis
Likely inborn error of metabolism - targeted testing not possible v0.4 NARS2 Ellen McDonagh Added phenotypes Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 24 for gene: NARS2
Publications for gene NARS2 were changed from 25629079; PMID: 25385316; 25807530 to 25629079; 25807530; 25385316
Likely inborn error of metabolism - targeted testing not possible v0.4 NARS2 Ellen McDonagh gene: NARS2 was added
gene: NARS2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: NARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NARS2 were set to 25629079; PMID: 25385316; 25807530
Phenotypes for gene: NARS2 were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 24
Likely inborn error of metabolism - targeted testing not possible v0.4 NAGLU Ellen McDonagh gene: NAGLU was added
gene: NAGLU was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: NAGLU was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NAGLU were set to 27604308
Phenotypes for gene: NAGLU were set to Mucopolysaccharidosis Type III; Mucopolysaccharidosis, Type III; Mucopolysaccharidosis type IIIB (Sanfilippo B), 252920; MPS IIIB, Sanfilippo B disease (Mucopolysaccharidoses); MUCOPOLYSACCHARIDOSIS TYPE 3B; Mucopolysaccharidosis Type IIIB
Likely inborn error of metabolism - targeted testing not possible v0.4 MVK Ellen McDonagh gene: MVK was added
gene: MVK was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: MVK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MVK were set to 27604308
Phenotypes for gene: MVK were set to Infantile enterocolitis & monogenic inflammatory bowel disease; Mevalonate kinase deficiency (Disorders of sterol biosynthesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 MUT Ellen McDonagh gene: MUT was added
gene: MUT was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: MUT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MUT were set to 27604308
Phenotypes for gene: MUT were set to metabolic encephalopathy with hyperammonaemia, hypotonia, recurrent episodes of ketoacidosis, liver impairment, psychomotor retardation, recurrent infections.; Methylmalonic aciduria, mut(0) type 251000; Methylmalonyl-CoA mutase deficiency (Organic acidurias)
Likely inborn error of metabolism - targeted testing not possible v0.4 MTTP Ellen McDonagh gene: MTTP was added
gene: MTTP was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: MTTP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTTP were set to 27604308
Phenotypes for gene: MTTP were set to Abetalipoproteinemia, 200100; (ACANTHOCYTOSIS, BASSEN-KORNZWEIG SYNDROME, MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN DEFICIENCY, MTP DEFICIENCY); Familial abetalipoproteinaemia (Inherited hypolipidaemias)
Likely inborn error of metabolism - targeted testing not possible v0.4 MTPAP Ellen McDonagh gene: MTPAP was added
gene: MTPAP was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: MTPAP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTPAP were set to 27604308
Phenotypes for gene: MTPAP were set to ?Spastic ataxia 4, autosomal recessive, 613672; Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)
Likely inborn error of metabolism - targeted testing not possible v0.4 MTO1 Ellen McDonagh Added phenotypes Combined oxidative phosphorylation deficiency 10, 614702; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); infantile hypertrophic cardiomyopathy and lactic acidosis. for gene: MTO1
Publications for gene MTO1 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 MTO1 Ellen McDonagh gene: MTO1 was added
gene: MTO1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: MTO1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MTO1 were set to Combined oxidative phosphorylation deficiency 10, 614702; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); infantile hypertrophic cardiomyopathy and lactic acidosis.
Likely inborn error of metabolism - targeted testing not possible v0.4 MTHFD1 Ellen McDonagh gene: MTHFD1 was added
gene: MTHFD1 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: MTHFD1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MTHFD1 were set to {Abruptio placentae, susceptibility to}; {Spina bifida, folate-sensitive, susceptibility to} 601634 AR
Likely inborn error of metabolism - targeted testing not possible v0.4 MTFMT Ellen McDonagh Added phenotypes Combined oxidative phosphorylation deficiency 15, 614947; Multiple respiratory chain complex deficiencies (disorders of protein synthesis) for gene: MTFMT
Likely inborn error of metabolism - targeted testing not possible v0.4 MTFMT Ellen McDonagh gene: MTFMT was added
gene: MTFMT was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: MTFMT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MTFMT were set to 27604308
Phenotypes for gene: MTFMT were set to Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Inherited white matter disorders
Likely inborn error of metabolism - targeted testing not possible v0.4 MSMO1 Ellen McDonagh gene: MSMO1 was added
gene: MSMO1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: MSMO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MSMO1 were set to 27604308
Phenotypes for gene: MSMO1 were set to Sterol-C4-methyl oxidase deficiency (Disorders of sterol biosynthesis); (SC4MOL DEFICIENCY); Microcephaly, congenital cataract, and psoriasiform dermatitis, 616834
Likely inborn error of metabolism - targeted testing not possible v0.4 MRPS22 Ellen McDonagh Added phenotypes Combined oxidative phosphorylation deficiency 5, 611719; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) for gene: MRPS22
Publications for gene MRPS22 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 MRPS22 Ellen McDonagh gene: MRPS22 was added
gene: MRPS22 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: MRPS22 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MRPS22 were set to Combined oxidative phosphorylation deficiency 5, 611719; Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 MRPS16 Ellen McDonagh Added phenotypes Combined oxidative phosphorylation deficiency 2, 610498; Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); CORPUS CALLOSUM, AGENESIS OF, WITH DYSMORPHISM AND FATAL LACTIC ACIDOSIS for gene: MRPS16
Publications for gene MRPS16 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 MRPS16 Ellen McDonagh gene: MRPS16 was added
gene: MRPS16 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: MRPS16 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MRPS16 were set to Combined oxidative phosphorylation deficiency 2, 610498; Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 MRPL3 Ellen McDonagh Added phenotypes Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 9, 614582 for gene: MRPL3
Likely inborn error of metabolism - targeted testing not possible v0.4 MRPL3 Ellen McDonagh gene: MRPL3 was added
gene: MRPL3 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: MRPL3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRPL3 were set to 27604308
Phenotypes for gene: MRPL3 were set to Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Combined oxidative phosphorylation deficiency 9, 614582
Likely inborn error of metabolism - targeted testing not possible v0.4 MMAB Ellen McDonagh gene: MMAB was added
gene: MMAB was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: MMAB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMAB were set to 27604308
Phenotypes for gene: MMAB were set to Defect in adenosylcobalamin synthesis-cbl B (Disorders of cobalamin absorption, transport and metabolism); Methylmalonic aciduria, vitamin B12-responsive, due to defect in synthesis of adenosylcobalamin, cblB complementation type 251110
Likely inborn error of metabolism - targeted testing not possible v0.4 MMAA Ellen McDonagh gene: MMAA was added
gene: MMAA was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: MMAA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMAA were set to 27604308
Phenotypes for gene: MMAA were set to Methylmalonic aciduria, vitamin B12-responsive 251100; Defect in adenosylcobalamin synthesis-cbl A (Disorders of cobalamin absorption, transport and metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 MGME1 Ellen McDonagh Added phenotypes Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Mitochondrial DNA depletion syndrome 11, 615084; Disorders of mitochondrial DNA maintenance and integrity for gene: MGME1
Likely inborn error of metabolism - targeted testing not possible v0.4 MGME1 Ellen McDonagh gene: MGME1 was added
gene: MGME1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: MGME1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MGME1 were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Mitochondrial DNA depletion syndrome 11, 615084; Disorders of mitochondrial DNA maintenance and integrity
Likely inborn error of metabolism - targeted testing not possible v0.4 MFF Ellen McDonagh Added phenotypes Encephalopathy due to defective mitochondrial and peroxisomal fission 2, 617086; Disorders of mitochondrial dynamics, fusion and fission (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) for gene: MFF
Publications for gene MFF were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 MFF Ellen McDonagh gene: MFF was added
gene: MFF was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: MFF was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MFF were set to Encephalopathy due to defective mitochondrial and peroxisomal fission 2
Likely inborn error of metabolism - targeted testing not possible v0.4 MCOLN1 Ellen McDonagh gene: MCOLN1 was added
gene: MCOLN1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: MCOLN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCOLN1 were set to 27604308
Phenotypes for gene: MCOLN1 were set to Mucolipidosis, Type IV; Mucolipidosis IV (Other lysosomal disorders)
Likely inborn error of metabolism - targeted testing not possible v0.4 MCEE Ellen McDonagh gene: MCEE was added
gene: MCEE was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: MCEE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCEE were set to 27604308
Phenotypes for gene: MCEE were set to Methylmalonyl-CoA epimerase deficiency (Organic acidurias); Methylmalonyl-CoA epimerase deficiency; metabolic encephalopathy with hyperammonaemia, hypotonia, recurrent episodes of ketoacidosis, liver impairment, psychomotor retardation, recurrent infections
Likely inborn error of metabolism - targeted testing not possible v0.4 MARS2 Ellen McDonagh Added phenotypes Spastic Ataxia 13, autosomal recessive, 611390; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); ?Combined oxidative phosphorylation deficiency 25 for gene: MARS2
Publications for gene MARS2 were changed from 25754315; PMID: 22448145 to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 MARS2 Ellen McDonagh gene: MARS2 was added
gene: MARS2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: MARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MARS2 were set to 25754315; PMID: 22448145
Phenotypes for gene: MARS2 were set to Spastic Ataxia 13, autosomal recessive, 611390; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); ?Combined oxidative phosphorylation deficiency 25
Likely inborn error of metabolism - targeted testing not possible v0.4 MANBA Ellen McDonagh gene: MANBA was added
gene: MANBA was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: MANBA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MANBA were set to 27604308
Phenotypes for gene: MANBA were set to Mannosidosis, beta
Likely inborn error of metabolism - targeted testing not possible v0.4 MAN2B1 Ellen McDonagh gene: MAN2B1 was added
gene: MAN2B1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: MAN2B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAN2B1 were set to 27604308
Phenotypes for gene: MAN2B1 were set to Mannosidosis, alpha-, types I and II
Likely inborn error of metabolism - targeted testing not possible v0.4 MAN1B1 Ellen McDonagh Added phenotypes MAN1B1-CDG (Disorders of protein N-glycosylation); Mental retardation, autosomal recessive 15 614202 for gene: MAN1B1
Publications for gene MAN1B1 were changed from 24348268 to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 MAN1B1 Ellen McDonagh gene: MAN1B1 was added
gene: MAN1B1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: MAN1B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAN1B1 were set to 24348268
Phenotypes for gene: MAN1B1 were set to MAN1B1-CDG (Disorders of protein N-glycosylation); Mental retardation, autosomal recessive 15 614202
Likely inborn error of metabolism - targeted testing not possible v0.4 LRPPRC Ellen McDonagh Added phenotypes Leigh syndrome, French-Canadian type, 220111; Mitochondrial Diseases; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Isolated complex IV deficiency; Complex IV (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors) for gene: LRPPRC
Publications for gene LRPPRC were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 LRPPRC Ellen McDonagh gene: LRPPRC was added
gene: LRPPRC was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: LRPPRC was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LRPPRC were set to Leigh syndrome, French-Canadian type, 220111; Mitochondrial Diseases; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Isolated complex IV deficiency
Likely inborn error of metabolism - targeted testing not possible v0.4 LPIN1 Ellen McDonagh gene: LPIN1 was added
gene: LPIN1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: LPIN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LPIN1 were set to 27604308
Phenotypes for gene: LPIN1 were set to Myoglobinuria, acute recurrent, autosomal recessive
Likely inborn error of metabolism - targeted testing not possible v0.4 LIPC Ellen McDonagh gene: LIPC was added
gene: LIPC was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: LIPC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LIPC were set to 27604308
Phenotypes for gene: LIPC were set to {Diabetes mellitus, noninsulin-dependent} 125853; Hepatic lipase deficiency (Inherited mixed hyperlipidaemias); Hepatic lipase deficiency, 614025; [High density lipoprotein cholesterol level QTL 12] 612797
Likely inborn error of metabolism - targeted testing not possible v0.4 LIAS Ellen McDonagh Added phenotypes Pyruvate dehydrogenase lipoic acid synthetase deficiency, 614462; Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) for gene: LIAS
Publications for gene LIAS were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 LFNG Ellen McDonagh Added phenotypes O-fucose-specific beta-1,3-N-acetylglucosaminyltransferase deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies); ?Spondylocostal dysostosis 3, autosomal recessive 609813 for gene: LFNG
Publications for gene LFNG were changed from 27604308 to 16385447
Likely inborn error of metabolism - targeted testing not possible v0.4 LFNG Ellen McDonagh gene: LFNG was added
gene: LFNG was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: LFNG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LFNG were set to 27604308
Phenotypes for gene: LFNG were set to O-fucose-specific beta-1,3-N-acetylglucosaminyltransferase deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies); ?Spondylocostal dysostosis 3, autosomal recessive, 609813; LFNG-CDG (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies)
Likely inborn error of metabolism - targeted testing not possible v0.4 LDLRAP1 Ellen McDonagh gene: LDLRAP1 was added
gene: LDLRAP1 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: LDLRAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LDLRAP1 were set to 27604308
Phenotypes for gene: LDLRAP1 were set to Familial hypercholesterolaemia; Autosomal recessive hypercholesterolemia (Inherited hypercholesterolaemias)
Likely inborn error of metabolism - targeted testing not possible v0.4 LCAT Ellen McDonagh gene: LCAT was added
gene: LCAT was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: LCAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LCAT were set to 27604308
Phenotypes for gene: LCAT were set to Norum disease/LCAT deficiency, 245900; Fish-eye disease, 136120; Lecithin cholesterol acyltransferase deficiency (Disorders of high density lipoprotein metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 LARS2 Ellen McDonagh Added phenotypes Perrault syndrome; Perrault syndrome 4, 615300; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) for gene: LARS2
Publications for gene LARS2 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 LARS2 Ellen McDonagh gene: LARS2 was added
gene: LARS2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: LARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LARS2 were set to Perrault syndrome; Perrault syndrome 4, 615300; Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 LARGE1 Ellen McDonagh Added phenotypes N-acetylglucosaminyltransferase-like protein deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies); Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 6 608840; N-acetylglucosaminyltransferase-like protein deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies); Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6 613154 for gene: LARGE1
Publications for gene LARGE1 were changed from 27421908 to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 LARGE1 Ellen McDonagh gene: LARGE1 was added
gene: LARGE1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: LARGE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LARGE1 were set to 27421908
Phenotypes for gene: LARGE1 were set to N-acetylglucosaminyltransferase-like protein deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies); Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 6 608840; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6 613154
Likely inborn error of metabolism - targeted testing not possible v0.4 KYNU Ellen McDonagh gene: KYNU was added
gene: KYNU was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: KYNU was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KYNU were set to 27604308; 17334708; 28792876
Phenotypes for gene: KYNU were set to Hydroxykynureninuria (Disorders of histidine, tryptophan or lysine metabolism); VACTERL-like phenotype; multiple congenital malformations; ?Hydroxykynureninuria, 236800
Likely inborn error of metabolism - targeted testing not possible v0.4 KARS Ellen McDonagh Added phenotypes Deafness, autosomal recessive 89, 613916; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Charcot-Marie-Tooth disease, recessive intermediate, B (Lysyl-tRNA synthetase mutations) (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Charcot-Marie-Tooth disease, recessive intermediate, B, 613641 for gene: KARS
Publications for gene KARS were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 KARS Ellen McDonagh gene: KARS was added
gene: KARS was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: KARS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: KARS were set to Deafness, autosomal recessive 89, 613916; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Charcot-Marie-Tooth disease, recessive intermediate, B, 613641
Likely inborn error of metabolism - targeted testing not possible v0.4 IVD Ellen McDonagh gene: IVD was added
gene: IVD was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: IVD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IVD were set to 27604308; 24816252
Phenotypes for gene: IVD were set to metabolic encephalopathy with hyperammonaemia, hypotonia, recurrent episodes of ketoacidosis, liver impairment, psychomotor retardation, recurrent infections.; Isovaleric acidemia; Isovaleric aciduria (Organic acidurias)
Likely inborn error of metabolism - targeted testing not possible v0.4 ITPA Ellen McDonagh gene: ITPA was added
gene: ITPA was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: ITPA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITPA were set to 27604308
Phenotypes for gene: ITPA were set to Inosine triphosphatase deficiency (Disorders of purine metabolism); Epileptic encephalopathy, early infantile, 35, 616647; [Inosine triphosphatase deficiency], 613850
Likely inborn error of metabolism - targeted testing not possible v0.4 ISCU Ellen McDonagh Added phenotypes Myopathy with lactic acidosis, hereditary, 255125; Disorders of iron homeostasis for gene: ISCU
Likely inborn error of metabolism - targeted testing not possible v0.4 ISCU Ellen McDonagh gene: ISCU was added
gene: ISCU was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: ISCU was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ISCU were set to 27604308
Phenotypes for gene: ISCU were set to Rhabdomyolysis and metabolic muscle disorders; Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only))
Likely inborn error of metabolism - targeted testing not possible v0.4 IDUA Ellen McDonagh gene: IDUA was added
gene: IDUA was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: IDUA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IDUA were set to 27604308
Phenotypes for gene: IDUA were set to Hurler syndrome; Mucopolysaccharidosis type 1H/S; MPS I, Hurler, Scheie disease (Mucopolysaccharidoses); Scheie syndrome; Hurler-Scheie syndrome; Mucopolysaccharidosis type 1S; Mucopolysaccharidosis type 1H; Mucopolysaccharidosis Ih/s, 607015; Mucopolysaccharidosis, Type I; Mucopolysaccharidosis Is, 607016; Mucopolysaccharidosis Ih, 607014
Likely inborn error of metabolism - targeted testing not possible v0.4 IBA57 Ellen McDonagh Added phenotypes ?Multiple mitochondrial dysfunctions syndrome 3, 615330; ?Spastic paraplegia 74, autosomal recessive for gene: IBA57
Publications for gene IBA57 were changed from PMID: 23462291; 25971455 to 23462291; 25971455
Likely inborn error of metabolism - targeted testing not possible v0.4 IBA57 Ellen McDonagh gene: IBA57 was added
gene: IBA57 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: IBA57 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IBA57 were set to PMID: 23462291; 25971455
Phenotypes for gene: IBA57 were set to ?Multiple mitochondrial dysfunctions syndrome 3, 615330; ?Spastic paraplegia 74, autosomal recessive
Likely inborn error of metabolism - targeted testing not possible v0.4 IARS2 Ellen McDonagh Added phenotypes CAGSSS - Cataracts (CA), growth hormone deficiency (G), sensory neuropathy (S), sensorineural hearing loss (S), and skeletal dysplasia (S); No OMIM phenotype for gene: IARS2
Publications for gene IARS2 were changed from 27604308; 25130867; 27078007 to PMID: 25130867 (3 related cases with CAGSSS homozygous for a rare nonsynonymous variant in this gene, an unrelated case with Leigh syndrome compound heterozygous for variants within this gene); PMID: 27078007 (full text not available to confirm findings).
Likely inborn error of metabolism - targeted testing not possible v0.4 IARS2 Ellen McDonagh gene: IARS2 was added
gene: IARS2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: IARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IARS2 were set to 27604308; 25130867; 27078007
Phenotypes for gene: IARS2 were set to Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only))
Likely inborn error of metabolism - targeted testing not possible v0.4 HYAL1 Ellen McDonagh gene: HYAL1 was added
gene: HYAL1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: HYAL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HYAL1 were set to 27604308
Phenotypes for gene: HYAL1 were set to ?Mucopolysaccharidosis type IX, 601492; MPS IX, Natowicz (MPS IV, Morquio disease)
Likely inborn error of metabolism - targeted testing not possible v0.4 HSPA9 Ellen McDonagh gene: HSPA9 was added
gene: HSPA9 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: HSPA9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HSPA9 were set to PMID: 26598328
Phenotypes for gene: HSPA9 were set to EVEN-PLUS syndrome of congenital malformations and skeletal dysplasia; Epiphyseal, Vertebral, Ear, Nose, plus associated findings
Likely inborn error of metabolism - targeted testing not possible v0.4 HSD3B7 Ellen McDonagh gene: HSD3B7 was added
gene: HSD3B7 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: HSD3B7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HSD3B7 were set to 27604308
Phenotypes for gene: HSD3B7 were set to 3- ?-hydroxysterol ?5-oxidoreductase/isomerase deficiency (Disorders of bile acid biosynthesis); Bile acid synthesis defect, congenital, 1, 607765
Likely inborn error of metabolism - targeted testing not possible v0.4 HLCS Ellen McDonagh Added phenotypes Holocarboxylase synthetase deficiency, 253270; Holocarboxylase synthetase deficiency; lactic acidosis with seizures and eczema, immune deficiency; Holocarboxylase synthetase deficiency (Disorders of biotin metabolism) for gene: HLCS
Publications for gene HLCS were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 HGSNAT Ellen McDonagh gene: HGSNAT was added
gene: HGSNAT was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: HGSNAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HGSNAT were set to 27604308
Phenotypes for gene: HGSNAT were set to Mucopolysaccharidosis Type III; Mucopolysaccharidosis, Type III; Retinitis Pigmentosa 73; Mucopolysaccharidosis type IIIC (Sanfilippo C), 252930; Mucopolysaccharidosis Type IIIC; MPS IIIC, Sanfilippo C disease (Mucopolysaccharidoses)
Likely inborn error of metabolism - targeted testing not possible v0.4 HFE2 Ellen McDonagh gene: HFE2 was added
gene: HFE2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: HFE2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HFE2 were set to 27604308
Phenotypes for gene: HFE2 were set to Hemochromatosis, type 2A, 602390; Hereditary haemochromatosis Type 2 (Disorder of iron metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 HFE Ellen McDonagh gene: HFE was added
gene: HFE was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: HFE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HFE were set to 27604308
Phenotypes for gene: HFE were set to Hemochromatosis, 235200; Hereditary haemochromatosis Type 1 (Disorder of iron metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 HEXA Ellen McDonagh gene: HEXA was added
gene: HEXA was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: HEXA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: HEXA were set to GM2-gangliosidosis, several forms
Likely inborn error of metabolism - targeted testing not possible v0.4 HARS2 Ellen McDonagh Added phenotypes Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Perrault syndrome 2, 614926 for gene: HARS2
Likely inborn error of metabolism - targeted testing not possible v0.4 HARS2 Ellen McDonagh gene: HARS2 was added
gene: HARS2 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: HARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HARS2 were set to 27604308
Phenotypes for gene: HARS2 were set to ?Perrault syndrome 2 614926; Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only))
Likely inborn error of metabolism - targeted testing not possible v0.4 HAMP Ellen McDonagh gene: HAMP was added
gene: HAMP was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: HAMP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HAMP were set to 27604308
Phenotypes for gene: HAMP were set to Hemochromatosis, type 2B 613313; Hereditary haemochromatosis Type 2 (Disorder of iron metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 GUSB Ellen McDonagh gene: GUSB was added
gene: GUSB was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: GUSB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GUSB were set to 27604308
Phenotypes for gene: GUSB were set to MUCOPOLYSACCHARIDOSIS TYPE 7; Mucopolysaccharidosis VII, 253220; MPS VII, Sly disease (MPS IV, Morquio disease); Mucopolysaccharidosis Type VII; Mucopolysaccharidosis, Type VII
Likely inborn error of metabolism - targeted testing not possible v0.4 GTPBP3 Ellen McDonagh Added phenotypes Combined oxidative phosphorylation deficiency 23; mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis and encephalopathy; Multiple respiratory chain complex deficiencies (disorders of protein synthesis) for gene: GTPBP3
Likely inborn error of metabolism - targeted testing not possible v0.4 GTPBP3 Ellen McDonagh gene: GTPBP3 was added
gene: GTPBP3 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: GTPBP3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GTPBP3 were set to Combined oxidative phosphorylation deficiency 23; mitochondrial translation defect associated with hypertrophic cardiomyopathy, lactic acidosis and encephalopathy; Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 GPD1 Ellen McDonagh gene: GPD1 was added
gene: GPD1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: GPD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPD1 were set to 24549054; 22226083
Phenotypes for gene: GPD1 were set to Hypertriglyceridemia, transient infantile, 614480
Likely inborn error of metabolism - targeted testing not possible v0.4 GNS Ellen McDonagh gene: GNS was added
gene: GNS was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: GNS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GNS were set to 27604308
Phenotypes for gene: GNS were set to MPS IIID, Sanfilippo D disease (Mucopolysaccharidoses); Mucopolysaccharidosis Type IIID; Mucopolysaccharidosis type IIID, 252940; Mucopolysaccharidosis Type III; Mucopolysaccharidosis, Type III
Likely inborn error of metabolism - targeted testing not possible v0.4 GNPTG Ellen McDonagh gene: GNPTG was added
gene: GNPTG was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: GNPTG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GNPTG were set to 27604308
Phenotypes for gene: GNPTG were set to Mucolipidosis III, Pseudo-Hurler polydystrophy (Other lysosomal disorders); mucolipidpsis type III complementation group C; Mucolipidosis, Type III Gamma; Mucolipidosis III gamma
Likely inborn error of metabolism - targeted testing not possible v0.4 GNPTAB Ellen McDonagh gene: GNPTAB was added
gene: GNPTAB was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: GNPTAB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GNPTAB were set to 27604308
Phenotypes for gene: GNPTAB were set to Mucolipidosis, Type II; Mucolipidosis, Type III Alpha/Beta; Mucolipidosis III alpha/beta; Mucolipidosis II, I-cell disease (Other lysosomal disorders); Mucolipidosis II alpha/beta
Likely inborn error of metabolism - targeted testing not possible v0.4 GNPAT Ellen McDonagh gene: GNPAT was added
gene: GNPAT was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: GNPAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GNPAT were set to 27604308
Phenotypes for gene: GNPAT were set to Rhizomelic chondrodysplasia punctata type 2 (Peroxisomal disorders); Rhizomelic chondrodysplasia punctata, type 2 222765
Likely inborn error of metabolism - targeted testing not possible v0.4 GNE Ellen McDonagh gene: GNE was added
gene: GNE was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: GNE was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GNE were set to 27604308
Phenotypes for gene: GNE were set to Nonaka myopathy 605820; ADUDP-GlcNAc epimerase/kinase deficiency (Disorders of multiple glycosylation and other glycosylation pathways); UDP-GlcNAc epimerase/kinase deficiency (Disorders of multiple glycosylation and other glycosylation pathways); Sialuria (Other lysosomal disorders)
Likely inborn error of metabolism - targeted testing not possible v0.4 GLRX5 Ellen McDonagh Added phenotypes Disorders of iron homeostasis; Anemia, sideroblastic, pyridoxine-refractory, autosomal recessive, 205950; Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) for gene: GLRX5
Publications for gene GLRX5 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 GLRX5 Ellen McDonagh gene: GLRX5 was added
gene: GLRX5 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: GLRX5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GLRX5 were set to Anemia, sideroblastic, pyridoxine-refractory, autosomal recessive, 205950; Disorders of iron homeostasis
Likely inborn error of metabolism - targeted testing not possible v0.4 GLB1 Ellen McDonagh gene: GLB1 was added
gene: GLB1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: GLB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GLB1 were set to 27604308
Phenotypes for gene: GLB1 were set to MUCOPOLYSACCHARIDOSIS TYPE 4B; MPS IVB, Morquio B disease (MPS IV, Morquio disease); Mucopolysaccharidosis type IVB (Morquio), 253010; GM1-gangliosidosis (Sphingolipidoses); GM1-gangliosidosis, type II, 230600; GM1-gangliosidosis, type III, 230650; Mucopolysaccharidosis, Type IV; Mucopolysaccharidosis Type IVB; GM1-gangliosidosis, type I, 230500
Likely inborn error of metabolism - targeted testing not possible v0.4 GIF Ellen McDonagh gene: GIF was added
gene: GIF was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: GIF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GIF were set to 27604308
Phenotypes for gene: GIF were set to Intrinsic factor deficiency
Likely inborn error of metabolism - targeted testing not possible v0.4 GFM1 Ellen McDonagh Added phenotypes Combined oxidative phosphorylation deficiency 1, 609060; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) for gene: GFM1
Publications for gene GFM1 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 GFM1 Ellen McDonagh gene: GFM1 was added
gene: GFM1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: GFM1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GFM1 were set to Combined oxidative phosphorylation deficiency 1, 609060; Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 GFER Ellen McDonagh Added phenotypes Myopathy, mitochondrial progressive, with congenital cataract, hearing loss, and developmental delay,613076; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Disorders of the mitochondrial import system; Disorders of mitochondrial protein import (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) for gene: GFER
Publications for gene GFER were changed from 19409522; PMID: 26018198 to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 GFER Ellen McDonagh gene: GFER was added
gene: GFER was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: GFER was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GFER were set to 19409522; PMID: 26018198
Phenotypes for gene: GFER were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Disorders of the mitochondrial import system; Myopathy, mitochondrial progressive, with congenital cataract, hearing loss, and developmental delay,613076
Likely inborn error of metabolism - targeted testing not possible v0.4 GALT Ellen McDonagh gene: GALT was added
gene: GALT was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: GALT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GALT were set to 27604308
Phenotypes for gene: GALT were set to Intellectual disability; Classical galactosaemia (Disorders of galactose metabolism); Galactosemia; Cataracts
Likely inborn error of metabolism - targeted testing not possible v0.4 GALNT3 Ellen McDonagh Added phenotypes Tumoral calcinosis, hyperphosphatemic, familial 211900; Polypeptide N-acetylgalactosaminyl transferase deficiency (Disorders of protein O-glycosylation, O-N-acetylgalactosaminylglycan synthesis deficiencies) for gene: GALNT3
Publications for gene GALNT3 were changed from 27604308 to 15133511
Likely inborn error of metabolism - targeted testing not possible v0.4 GALNT3 Ellen McDonagh gene: GALNT3 was added
gene: GALNT3 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: GALNT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GALNT3 were set to 27604308
Phenotypes for gene: GALNT3 were set to Polypeptide N-acetylgalactosaminyl transferase deficiency (Disorders of protein O-glycosylation, O-N-acetylgalactosaminylglycan synthesis deficiencies); Tumoral calcinosis, hyperphosphatemic, familial 211900
Likely inborn error of metabolism - targeted testing not possible v0.4 GALNS Ellen McDonagh gene: GALNS was added
gene: GALNS was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: GALNS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GALNS were set to 27604308
Phenotypes for gene: GALNS were set to MUCOPOLYSACCHARIDOSIS TYPE 4A; Mucopolysaccharidosis Type IVA; Mucopolysaccharidosis IVA, 253000; Mucopolysaccharidosis, Type IV; MPS IVA, Morquio A disease (MPS IV, Morquio disease)
Likely inborn error of metabolism - targeted testing not possible v0.4 FXN Ellen McDonagh gene: FXN was added
gene: FXN was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: FXN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FXN were set to 27604308
Phenotypes for gene: FXN were set to Hereditary ataxia; Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only))
Likely inborn error of metabolism - targeted testing not possible v0.4 FLAD1 Ellen McDonagh gene: FLAD1 was added
gene: FLAD1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: FLAD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FLAD1 were set to PubMed: 27259049
Phenotypes for gene: FLAD1 were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Multiple acyl-CoA dehydrogenase deficiencies (MADDs)
Likely inborn error of metabolism - targeted testing not possible v0.4 FKTN Ellen McDonagh Added phenotypes Muscular dystrophy-dystroglycanopathy (congenital without mental retardation), type B, 4 613152; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 253800; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 4 611588; Fukutin deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies) for gene: FKTN
Publications for gene FKTN were changed from 27421908 to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 FKTN Ellen McDonagh gene: FKTN was added
gene: FKTN was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: FKTN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FKTN were set to 27421908
Phenotypes for gene: FKTN were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 253800; Fukutin deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies); Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 4 611588; Muscular dystrophy-dystroglycanopathy (congenital without mental retardation), type B, 4 613152
Likely inborn error of metabolism - targeted testing not possible v0.4 FKRP Ellen McDonagh Added phenotypes Muscular dystrophy-dystroglycanopathy (congenital with or without mental retardation), type B, 5 606612; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5 613153; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 5 607155; Fukutin-related protein deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies) for gene: FKRP
Publications for gene FKRP were changed from 27421908 to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 FECH Ellen McDonagh gene: FECH was added
gene: FECH was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: FECH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FECH were set to 27604308
Phenotypes for gene: FECH were set to Erythropoietic protoporphyria, mild variant; Erythropoietic protoporphyria (Porphyrias with acute painful photosensitivity)
Likely inborn error of metabolism - targeted testing not possible v0.4 FBXL4 Ellen McDonagh Added phenotypes fatal encephalopathy, lactic acidosis, and severe MTDNA depletion in muscle.; Disorders of mitochondrial DNA maintenance and integrity; Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type), 615471 for gene: FBXL4
Likely inborn error of metabolism - targeted testing not possible v0.4 FBXL4 Ellen McDonagh gene: FBXL4 was added
gene: FBXL4 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: FBXL4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FBXL4 were set to fatal encephalopathy, lactic acidosis, and severe MTDNA depletion in muscle.; Disorders of mitochondrial DNA maintenance and integrity; Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type), 615471
Likely inborn error of metabolism - targeted testing not possible v0.4 FBP1 Ellen McDonagh gene: FBP1 was added
gene: FBP1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: FBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FBP1 were set to 27604308
Phenotypes for gene: FBP1 were set to Glycogen Storage Disease; Glycogen Storage Disorders- Liver; Fructose-1,6-bisphosphatase deficiency (Disorders of gluconeogenesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 FARS2 Ellen McDonagh Added phenotypes Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Combined oxidative phosphorylation deficiency 14, 614946 for gene: FARS2
Publications for gene FARS2 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 FARS2 Ellen McDonagh gene: FARS2 was added
gene: FARS2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: FARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FARS2 were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 14, 614946
Likely inborn error of metabolism - targeted testing not possible v0.4 FAH Ellen McDonagh gene: FAH was added
gene: FAH was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: FAH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAH were set to 27604308
Phenotypes for gene: FAH were set to Tyrosinemia, type I
Likely inborn error of metabolism - targeted testing not possible v0.4 FA2H Ellen McDonagh gene: FA2H was added
gene: FA2H was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: FA2H was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FA2H were set to 27604308
Phenotypes for gene: FA2H were set to Fatty acid 2-hydroxylase deficiency (Disorders of complex lipid synthesis); Early onset dystonia; Neurodegeneration with brain iron accumulation (NBIA) (Disorder of iron metabolism); Hereditary spastic paraplegia
Likely inborn error of metabolism - targeted testing not possible v0.4 EXT1 Ellen McDonagh Added phenotypes Multiple exostoses type I (Disorders of protein O-glycosylation, O-xylosylglycan synthesis deficiencies); Exostoses, multiple, type 1 133700 for gene: EXT1
Publications for gene EXT1 were changed from 12417417 to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 EXT1 Ellen McDonagh gene: EXT1 was added
gene: EXT1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: EXT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXT1 were set to 12417417
Phenotypes for gene: EXT1 were set to Multiple exostoses type I (Disorders of protein O-glycosylation, O-xylosylglycan synthesis deficiencies); Exostoses, multiple, type 1 133700
Likely inborn error of metabolism - targeted testing not possible v0.4 ETHE1 Ellen McDonagh Added phenotypes Ethylmalonic encephalopathy, 602473; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Isolated complex IV deficiency; Complex IV (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors); Ethylmalonic encephalopathy for gene: ETHE1
Publications for gene ETHE1 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 ETHE1 Ellen McDonagh gene: ETHE1 was added
gene: ETHE1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: ETHE1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ETHE1 were set to Ethylmalonic encephalopathy, 602473; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Isolated complex IV deficiency; Ethylmalonic encephalopathy
Likely inborn error of metabolism - targeted testing not possible v0.4 ETFDH Ellen McDonagh Added phenotypes GLUTARIC ACIDURIA TYPE 2C; Glutaric acidemia IIC; Disorders of ubiquinone metabolism and biosynthesis for gene: ETFDH
Likely inborn error of metabolism - targeted testing not possible v0.4 ETFDH Ellen McDonagh gene: ETFDH was added
gene: ETFDH was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: ETFDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ETFDH were set to 27604308; 24816252
Phenotypes for gene: ETFDH were set to Secondary CoQ10 deficiency (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of ubiquinone metabolism and biosynthesis; GLUTARIC ACIDURIA TYPE 2C; Glutaric acidemia IIC; ETF-ubiquinone oxidoreductase deficiency (Disorders of mitochondrial fatty acid oxidation)
Likely inborn error of metabolism - targeted testing not possible v0.4 EPM2A Ellen McDonagh gene: EPM2A was added
gene: EPM2A was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: EPM2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EPM2A were set to 27604308
Phenotypes for gene: EPM2A were set to Epilepsy, progressive myoclonic 2A (Lafora)
Likely inborn error of metabolism - targeted testing not possible v0.4 ELAC2 Ellen McDonagh Added phenotypes infantile hypertrophic cardiomyopathy, lactic acidosis, and isolated complex I deficiency; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 17, 615440 for gene: ELAC2
Likely inborn error of metabolism - targeted testing not possible v0.4 ELAC2 Ellen McDonagh gene: ELAC2 was added
gene: ELAC2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: ELAC2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ELAC2 were set to infantile hypertrophic cardiomyopathy, lactic acidosis, and isolated complex I deficiency; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 17, 615440
Likely inborn error of metabolism - targeted testing not possible v0.4 EGF Ellen McDonagh gene: EGF was added
gene: EGF was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: EGF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EGF were set to 27604308
Phenotypes for gene: EGF were set to Hypomagnesaemia type 4, renal (Disorder of magnesium metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 EARS2 Ellen McDonagh Added phenotypes Combined oxidative phosphorylation deficiency 12, 614924; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) for gene: EARS2
Publications for gene EARS2 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 EARS2 Ellen McDonagh gene: EARS2 was added
gene: EARS2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: EARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: EARS2 were set to Combined oxidative phosphorylation deficiency 12, 614924; Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 DYM Ellen McDonagh Added phenotypes Encephalopahty, lethal, due to defective mitochondrial peroxisomal fission, 614388 for gene: DYM
Likely inborn error of metabolism - targeted testing not possible v0.4 DYM Ellen McDonagh gene: DYM was added
gene: DYM was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: DYM was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DYM were set to Dyggve-Melchior-Clausen disease, 223800; Smith-McCort dysplasia, 607326
Likely inborn error of metabolism - targeted testing not possible v0.4 DHODH Ellen McDonagh gene: DHODH was added
gene: DHODH was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: DHODH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHODH were set to 27604308
Phenotypes for gene: DHODH were set to Unexplained skeletal dysplasia; Bilateral microtia; Deafness and congenital structural abnormalities; Dihydroorotate dehydrogenase deficiency (Disorders of pyrimidine metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 DHCR7 Ellen McDonagh gene: DHCR7 was added
gene: DHCR7 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: DHCR7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHCR7 were set to 27604308
Phenotypes for gene: DHCR7 were set to Intellectual disability; IUGR and IGF abnormalities; Smith - Lemli - Opitz syndrome (Disorders of sterol biosynthesis); Disorders of sex development; Cataracts
Likely inborn error of metabolism - targeted testing not possible v0.4 DHCR24 Ellen McDonagh gene: DHCR24 was added
gene: DHCR24 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: DHCR24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHCR24 were set to 27604308
Phenotypes for gene: DHCR24 were set to Desmosterolosis (Disorders of sterol biosynthesis); Unexplained skeletal dysplasia; Intellectual disability
Likely inborn error of metabolism - targeted testing not possible v0.4 DGUOK Ellen McDonagh gene: DGUOK was added
gene: DGUOK was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: DGUOK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DGUOK were set to 27604308
Phenotypes for gene: DGUOK were set to Deoxyguanosine kinase deficiency (Disorders of purine metabolism); Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), 251880; Mitochondrial DNA Depletion Syndrome; Disorders of mitochondrial DNA maintenance and integrity; Required for mtDNA maintenance (Mitochondrial respiratory chain disorders (caused by nuclear variants only))
Likely inborn error of metabolism - targeted testing not possible v0.4 DCC Ellen McDonagh gene: DCC was added
gene: DCC was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: DCC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DCC were set to 28250456
Phenotypes for gene: DCC were set to Gaze palsy, familial horizontal, with progressive scoliosis, 2
Likely inborn error of metabolism - targeted testing not possible v0.4 DBT Ellen McDonagh gene: DBT was added
gene: DBT was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: DBT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DBT were set to 27604308
Phenotypes for gene: DBT were set to Dihydrolipoamide branched chain transacylase deficiency (Maple syrup urine disease, disorder of branched-chain amino acid metabolism not classified as organic aciduria); Maple syrup urine disease, type II
Likely inborn error of metabolism - targeted testing not possible v0.4 DARS2 Ellen McDonagh Added phenotypes Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, 611105; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) for gene: DARS2
Publications for gene DARS2 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 DARS2 Ellen McDonagh gene: DARS2 was added
gene: DARS2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: DARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DARS2 were set to Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, 611105; Multiple respiratory chain complex deficiencies (disorders of protein synthesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 CYP7B1 Ellen McDonagh gene: CYP7B1 was added
gene: CYP7B1 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: CYP7B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP7B1 were set to 27604308; 9802883
Phenotypes for gene: CYP7B1 were set to Bile acid synthesis defect, congenital, 3
Likely inborn error of metabolism - targeted testing not possible v0.4 CYP7A1 Ellen McDonagh gene: CYP7A1 was added
gene: CYP7A1 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: CYP7A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP7A1 were set to 27604308
Phenotypes for gene: CYP7A1 were set to Cholesterol 7-alpha-hydroxylase deficiency (Disorders of bile acid biosynthesis); Hypercholesterolemia due to cholesterol 7alpha-hydroxylase deficiency
Likely inborn error of metabolism - targeted testing not possible v0.4 CYP27A1 Ellen McDonagh gene: CYP27A1 was added
gene: CYP27A1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: CYP27A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP27A1 were set to 27604308
Phenotypes for gene: CYP27A1 were set to Cerebrotendinous xanthomatosis
Likely inborn error of metabolism - targeted testing not possible v0.4 CUBN Ellen McDonagh gene: CUBN was added
gene: CUBN was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: CUBN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CUBN were set to Intrinsic factor receptor deficiency due to CUBN mutations (Disorders of cobalamin absorption, transport and metabolism); Megaloblastic anemia-1, Finnish type; Proteinuric renal disease; Unexplained kidney failure in young people
Likely inborn error of metabolism - targeted testing not possible v0.4 CTSK Ellen McDonagh gene: CTSK was added
gene: CTSK was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: CTSK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTSK were set to 27604308
Phenotypes for gene: CTSK were set to Pycnodysostosis
Likely inborn error of metabolism - targeted testing not possible v0.4 CTSC Ellen McDonagh gene: CTSC was added
gene: CTSC was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: CTSC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTSC were set to 27604308
Phenotypes for gene: CTSC were set to Papillon-Lef vre syndrome (Other lysosomal disorders, Cathepsin-related disorders); Unexplained skeletal dysplasia
Likely inborn error of metabolism - targeted testing not possible v0.4 CTSA Ellen McDonagh gene: CTSA was added
gene: CTSA was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: CTSA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTSA were set to 27604308
Phenotypes for gene: CTSA were set to Galactosialidosis
Likely inborn error of metabolism - targeted testing not possible v0.4 CTNS Ellen McDonagh gene: CTNS was added
gene: CTNS was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: CTNS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTNS were set to 219750
Phenotypes for gene: CTNS were set to Cystinosis, atypical nephropathic
Likely inborn error of metabolism - targeted testing not possible v0.4 COX6A1 Ellen McDonagh Added phenotypes Charcot-Marie-Tooth disease, recessive intermediate D, 616039 for gene: COX6A1
Likely inborn error of metabolism - targeted testing not possible v0.4 COX6A1 Ellen McDonagh gene: COX6A1 was added
gene: COX6A1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: COX6A1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: COX6A1 were set to Charcot-Marie-Tooth disease, recessive intermediate D, 616039
Likely inborn error of metabolism - targeted testing not possible v0.4 COX4I2 Ellen McDonagh Added phenotypes Exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis, 612714; Mitochondrial Diseases for gene: COX4I2
Likely inborn error of metabolism - targeted testing not possible v0.4 COX4I2 Ellen McDonagh gene: COX4I2 was added
gene: COX4I2 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: COX4I2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COX4I2 were set to 27604308
Phenotypes for gene: COX4I2 were set to Complex IV (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS structural subunits); Exocrine pancreatic insufficiency, dyserythropoietic anemia, and calvarial hyperostosis 612714
Likely inborn error of metabolism - targeted testing not possible v0.4 COX10 Ellen McDonagh Added phenotypes Encephalopathy, progressive mitochondrial, with proximal renal tubulopathy due to cytochrome coxidase deficiency; Mitochondrial Diseases; Mitochondrial Respiratory Chain Complex IV Deficiency; Isolated complex IV deficiency; Complex IV (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors) for gene: COX10
Publications for gene COX10 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 COX10 Ellen McDonagh gene: COX10 was added
gene: COX10 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: COX10 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: COX10 were set to Encephalopathy, progressive mitochondrial, with proximal renal tubulopathy due to cytochrome coxidase deficiency; Mitochondrial Diseases; Mitochondrial Respiratory Chain Complex IV Deficiency; Isolated complex IV deficiency
Likely inborn error of metabolism - targeted testing not possible v0.4 COQ9 Ellen McDonagh Added phenotypes Coenzyme Q10 deficiency, primary, 5, 614654; Coenzyme Q10 deficiency; Disorders of CoQ10 biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of ubiquinone metabolism and biosynthesis for gene: COQ9
Publications for gene COQ9 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 COQ9 Ellen McDonagh gene: COQ9 was added
gene: COQ9 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: COQ9 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: COQ9 were set to Coenzyme Q10 deficiency, primary, 5, 614654; Coenzyme Q10 deficiency; Disorders of ubiquinone metabolism and biosynthesis
Likely inborn error of metabolism - targeted testing not possible v0.4 COQ8A Ellen McDonagh Added phenotypes Coenzyme Q10 deficiency; Disorders of CoQ10 biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of ubiquinone metabolism and biosynthesis; Coenzyme Q10 deficiency, primary, 4, 612016 for gene: COQ8A
Publications for gene COQ8A were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 COQ8A Ellen McDonagh gene: COQ8A was added
gene: COQ8A was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: COQ8A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: COQ8A were set to Coenzyme Q10 deficiency; Disorders of ubiquinone metabolism and biosynthesis; Coenzyme Q10 deficiency, primary, 4, 612016
Likely inborn error of metabolism - targeted testing not possible v0.4 COQ6 Ellen McDonagh Added phenotypes Coenzyme Q10 deficiency, primary, 6, 614650; Steroid-resistant nephrotic syndrome; Disorders of CoQ10 biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of ubiquinone metabolism and biosynthesis for gene: COQ6
Publications for gene COQ6 were changed from PMID: 21540551 to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 COQ6 Ellen McDonagh gene: COQ6 was added
gene: COQ6 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: COQ6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ6 were set to PMID: 21540551
Phenotypes for gene: COQ6 were set to Coenzyme Q10 deficiency, primary, 6, 614650; Steroid-resistant nephrotic syndrome; Disorders of ubiquinone metabolism and biosynthesis
Likely inborn error of metabolism - targeted testing not possible v0.4 COQ4 Ellen McDonagh Added phenotypes Disorders of CoQ10 biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Disorders of ubiquinone metabolism and biosynthesis; Coenzyme Q10 deficiency, primary, 7 for gene: COQ4
Publications for gene COQ4 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 COQ4 Ellen McDonagh gene: COQ4 was added
gene: COQ4 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: COQ4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: COQ4 were set to Disorders of ubiquinone metabolism and biosynthesis; Coenzyme Q10 deficiency, primary, 7
Likely inborn error of metabolism - targeted testing not possible v0.4 COQ2 Ellen McDonagh Added phenotypes {Multiple system atrophy, susceptibility to}, 146500; Coenzyme Q10 deficiency; 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 for gene: COQ2
Publications for gene COQ2 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 COQ2 Ellen McDonagh gene: COQ2 was added
gene: COQ2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: COQ2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: COQ2 were set to {Multiple system atrophy, susceptibility to}, 146500; Coenzyme Q10 deficiency; Disorders of ubiquinone metabolism and biosynthesis; Coenzyme Q10 deficiency, primary, 1, 607426
Likely inborn error of metabolism - targeted testing not possible v0.4 CLPB Ellen McDonagh Added phenotypes 3-methylglutaconic aciduria with the following: cataract, renal cysts and nephrocalcinosis; cataract, neutropenia, epilepsy; congenital microcephaly and severe encephalopathy; progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder for gene: CLPB
Publications for gene CLPB were changed from PMID: 25597510; PMID: 25650066; PMID: 25597511; PMID: 25595726 to 25597510; 25597511; 25650066; 25595726
Likely inborn error of metabolism - targeted testing not possible v0.4 CLPB Ellen McDonagh gene: CLPB was added
gene: CLPB was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: CLPB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLPB were set to PMID: 25597510; PMID: 25650066; PMID: 25597511; PMID: 25595726
Phenotypes for gene: CLPB were set to 3-methylglutaconic aciduria with the following: cataract, renal cysts and nephrocalcinosis; cataract, neutropenia, epilepsy; congenital microcephaly and severe encephalopathy; progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder
Likely inborn error of metabolism - targeted testing not possible v0.4 CLN8 Ellen McDonagh gene: CLN8 was added
gene: CLN8 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: CLN8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CLN8 were set to Ceroid lipofuscinosis, neuronal, 8
Likely inborn error of metabolism - targeted testing not possible v0.4 CLDN19 Ellen McDonagh gene: CLDN19 was added
gene: CLDN19 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: CLDN19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLDN19 were set to 27604308
Phenotypes for gene: CLDN19 were set to Hypomagnesaemia type 5, renal with ocular involvement (Disorder of magnesium metabolism); Renal tract calcification (or Nephrolithiasis/nephrocalcinosis)
Likely inborn error of metabolism - targeted testing not possible v0.4 CLDN16 Ellen McDonagh gene: CLDN16 was added
gene: CLDN16 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: CLDN16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLDN16 were set to 27604308
Phenotypes for gene: CLDN16 were set to Renal tract calcification (or Nephrolithiasis/nephrocalcinosis); Hypomagnesaemia type 3, renal (Disorder of magnesium metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 CHSY1 Ellen McDonagh Added phenotypes Temtamy preaxial brachydactyly syndrome 605282; CHSY1-CDG (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies) for gene: CHSY1
Publications for gene CHSY1 were changed from 27604308 to 24269551; 21129727
Likely inborn error of metabolism - targeted testing not possible v0.4 CHSY1 Ellen McDonagh gene: CHSY1 was added
gene: CHSY1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: CHSY1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHSY1 were set to 27604308
Phenotypes for gene: CHSY1 were set to Temtamy preaxial brachydactyly syndrome 605282; CHSY1-CDG (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies)
Likely inborn error of metabolism - targeted testing not possible v0.4 CHST6 Ellen McDonagh Added phenotypes CHST6-CDG (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies); Macular corneal dystrophy 217800 for gene: CHST6
Publications for gene CHST6 were changed from 16568029 to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 CHST6 Ellen McDonagh gene: CHST6 was added
gene: CHST6 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: CHST6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHST6 were set to 16568029
Phenotypes for gene: CHST6 were set to CHST6-CDG (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies); Macular corneal dystrophy 217800
Likely inborn error of metabolism - targeted testing not possible v0.4 CHST3 Ellen McDonagh Added phenotypes Spondyloepiphyseal dysplasia with congenital joint dislocations 143095; CHST3-CDG (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies) for gene: CHST3
Publications for gene CHST3 were changed from 27604308 to 20830804
Likely inborn error of metabolism - targeted testing not possible v0.4 CHST3 Ellen McDonagh gene: CHST3 was added
gene: CHST3 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: CHST3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHST3 were set to 27604308
Phenotypes for gene: CHST3 were set to Spondyloepiphyseal dysplasia with congenital joint dislocations 143095; CHST3-CDG (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies)
Likely inborn error of metabolism - targeted testing not possible v0.4 CHST14 Ellen McDonagh Added phenotypes Ehlers-Danlos syndrome, musculocontractural type 1 601776; CHST14-CDG (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies) for gene: CHST14
Publications for gene CHST14 were changed from 26646600 to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 CHST14 Ellen McDonagh gene: CHST14 was added
gene: CHST14 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: CHST14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHST14 were set to 26646600
Phenotypes for gene: CHST14 were set to Ehlers-Danlos syndrome, musculocontractural type 1 601776; CHST14-CDG (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies)
Likely inborn error of metabolism - targeted testing not possible v0.4 CHKB Ellen McDonagh gene: CHKB was added
gene: CHKB was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: CHKB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHKB were set to 27604308
Phenotypes for gene: CHKB were set to Choline kinase deficiency (Disorders of complex lipid synthesis); Muscular dystrophy, congenital, megaconial type, 602541
Likely inborn error of metabolism - targeted testing not possible v0.4 CBS Ellen McDonagh gene: CBS was added
gene: CBS was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: CBS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CBS were set to Homocystinuria, B6-responsive and nonresponsive types
Likely inborn error of metabolism - targeted testing not possible v0.4 CARS2 Ellen McDonagh gene: CARS2 was added
gene: CARS2 was added to Inborn errors of metabolism. Sources: Expert Review Red
Mode of inheritance for gene: CARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CARS2 were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); No OMIM phenotype
Likely inborn error of metabolism - targeted testing not possible v0.4 C12orf65 Ellen McDonagh Added phenotypes Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Spastic paraplegia 55, autosomal recessive, 615035; Combined oxidative phosphorylation deficiency 7, 613559 for gene: C12orf65
Publications for gene C12orf65 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 C12orf65 Ellen McDonagh gene: C12orf65 was added
gene: C12orf65 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: C12orf65 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: C12orf65 were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Spastic paraplegia 55, autosomal recessive, 615035; Combined oxidative phosphorylation deficiency 7, 613559
Likely inborn error of metabolism - targeted testing not possible v0.4 BTD Ellen McDonagh gene: BTD was added
gene: BTD was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: BTD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BTD were set to 27604308
Phenotypes for gene: BTD were set to Biotinidase deficiency (Disorders of biotin metabolism); Biotinidase deficiency; lactic acidosis with seizures and eczema,immune deficiency
Likely inborn error of metabolism - targeted testing not possible v0.4 BOLA3 Ellen McDonagh Added phenotypes Disorders of iron homeostasis; Multiple Mitochondrial Dysfunctions Syndrome; Hyperglycinaemia, non-ketotic (Baker (2014) Brain 137,366); Multiple mitochondrial dysfunctions syndrome 2, 614299; Defective Fe-S/lipoic acid biosynthesis (Mitochondrial respiratory chain disorders (caused by nuclear variants only)) for gene: BOLA3
Publications for gene BOLA3 were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 BOLA3 Ellen McDonagh gene: BOLA3 was added
gene: BOLA3 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: BOLA3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: BOLA3 were set to Hyperglycinaemia, non-ketotic (Baker (2014) Brain 137,366); Multiple Mitochondrial Dysfunctions Syndrome; Multiple mitochondrial dysfunctions syndrome 2, 614299; Disorders of iron homeostasis
Likely inborn error of metabolism - targeted testing not possible v0.4 BCKDHB Ellen McDonagh gene: BCKDHB was added
gene: BCKDHB was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: BCKDHB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BCKDHB were set to 27604308
Phenotypes for gene: BCKDHB were set to Maple syrup urine disease, type Ib; BCKD E1 beta subunit of deficiency (Maple syrup urine disease, disorder of branched-chain amino acid metabolism not classified as organic aciduria)
Likely inborn error of metabolism - targeted testing not possible v0.4 BCKDHA Ellen McDonagh gene: BCKDHA was added
gene: BCKDHA was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: BCKDHA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BCKDHA were set to 27604308
Phenotypes for gene: BCKDHA were set to Maple syrup urine disease, type Ia; BCKD E1 alpha subunit of deficiency (Maple syrup urine disease, disorder of branched-chain amino acid metabolism not classified as organic aciduria)
Likely inborn error of metabolism - targeted testing not possible v0.4 B4GALT7 Ellen McDonagh Added phenotypes Ehlers-Danlos syndrome with short stature and limb anomalies 130070; B4GALT7-CDG (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies); B4GALT7-CDG (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies, Disorders of protein O-glycosylation, O-xylosylglycan synthesis deficiencies); Beta-1,4-galactosyltransferase 7 deficiency (Disorders of protein O-glycosylation, O-xylosylglycan synthesis deficiencies) for gene: B4GALT7
Publications for gene B4GALT7 were changed from 27827381 to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 B4GALT7 Ellen McDonagh gene: B4GALT7 was added
gene: B4GALT7 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: B4GALT7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B4GALT7 were set to 27827381
Phenotypes for gene: B4GALT7 were set to Ehlers-Danlos syndrome with short stature and limb anomalies 130070; B4GALT7-CDG (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies, Disorders of protein O-glycosylation, O-xylosylglycan synthesis deficiencies)
Likely inborn error of metabolism - targeted testing not possible v0.4 B3GLCT Ellen McDonagh Added phenotypes Peters-plus syndrome 261540; O-fucose-specific beta-1,3-N-glucosyltransferase deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies) for gene: B3GLCT
Publications for gene B3GLCT were changed from 27604308 to 23889335; 16909395
Likely inborn error of metabolism - targeted testing not possible v0.4 B3GLCT Ellen McDonagh gene: B3GLCT was added
gene: B3GLCT was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: B3GLCT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B3GLCT were set to 27604308
Phenotypes for gene: B3GLCT were set to Peters-plus syndrome 261540; O-fucose-specific beta-1,3-N-glucosyltransferase deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies); O-fucose-specific beta-1,3-N-glucosyltransferase deficiency (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies)
Likely inborn error of metabolism - targeted testing not possible v0.4 B3GAT3 Ellen McDonagh Added phenotypes Multiple joint dislocations, short stature, craniofacial dysmorphism, with or without congenital heart defects 245600; B3GAT3-CDG (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies) for gene: B3GAT3
Publications for gene B3GAT3 were changed from 27871226; 26086840; 21763480 to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 B3GAT3 Ellen McDonagh gene: B3GAT3 was added
gene: B3GAT3 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: B3GAT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B3GAT3 were set to 27871226; 26086840; 21763480
Phenotypes for gene: B3GAT3 were set to Multiple joint dislocations, short stature, craniofacial dysmorphism, with or without congenital heart defects 245600; B3GAT3-CDG (Disorders of protein O-glycosylation, O-mannosylglycan synthesis deficiencies)
Likely inborn error of metabolism - targeted testing not possible v0.4 ATP6V0A2 Ellen McDonagh Added phenotypes V0 subunit A2 of vesicular H(+)-ATPase deficiency (Disorders of multiple glycosylation and other glycosylation pathways, V-ATPase deficiencies); Cutis laxa, autosomal recessive, type IIA 21920; Wrinkly skin syndrome 278250 for gene: ATP6V0A2
Publications for gene ATP6V0A2 were changed from 20301755 to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 ATP6V0A2 Ellen McDonagh gene: ATP6V0A2 was added
gene: ATP6V0A2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: ATP6V0A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP6V0A2 were set to 20301755
Phenotypes for gene: ATP6V0A2 were set to V0 subunit A2 of vesicular H(+)-ATPase deficiency (Disorders of multiple glycosylation and other glycosylation pathways, V-ATPase deficiencies); Cutis laxa, autosomal recessive, type IIA 21920; Wrinkly skin syndrome 278250
Likely inborn error of metabolism - targeted testing not possible v0.4 ATP5A1 Ellen McDonagh Added phenotypes ?Combined oxidative phosphorylation deficiency 22; ?Mitochondrial complex (ATP synthase) deficiency, nuclear type 4 for gene: ATP5A1
Publications for gene ATP5A1 were changed from 27604308 to PMID: 23599390 (two siblings with a severe neonatal encephalopathy caused by complex V deficiency); PMID: 23596069 (newborn female with failure to thrive, microcephaly, encephalopathy, IUGR, hypotonia, bacteremia, pulmonary hypertension, heart failure, and mitchondrial depletion).
Likely inborn error of metabolism - targeted testing not possible v0.4 ARSB Ellen McDonagh gene: ARSB was added
gene: ARSB was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: ARSB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARSB were set to 27604308
Phenotypes for gene: ARSB were set to MUCOPOLYSACCHARIDOSIS TYPE 6; Mucopolysaccharidosis, Type VI; Mucopolysaccharidosis type VI (Maroteaux-Lamy), 253200; Mucopolysaccharidosis Type VI; MPS VI, Maroteaux - Lamy disease (MPS IV, Morquio disease)
Likely inborn error of metabolism - targeted testing not possible v0.4 APTX Ellen McDonagh Added phenotypes Ataxia with oculomotor apraxia 1; Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia, 208920; Disorders of ubiquinone metabolism and biosynthesis for gene: APTX
Likely inborn error of metabolism - targeted testing not possible v0.4 APTX Ellen McDonagh gene: APTX was added
gene: APTX was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: APTX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: APTX were set to 27604308
Phenotypes for gene: APTX were set to Secondary CoQ10 deficiency (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Ataxia with oculomotor apraxia 1; Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia, 208920; Disorders of ubiquinone metabolism and biosynthesis
Likely inborn error of metabolism - targeted testing not possible v0.4 ANO10 Ellen McDonagh Added phenotypes Spinocerebellar ataxia, autosomal recessive 10, 613728 for gene: ANO10
Likely inborn error of metabolism - targeted testing not possible v0.4 ANO10 Ellen McDonagh gene: ANO10 was added
gene: ANO10 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: ANO10 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ANO10 were set to Spinocerebellar ataxia, autosomal recessive 10, 613728
Likely inborn error of metabolism - targeted testing not possible v0.4 AMN Ellen McDonagh gene: AMN was added
gene: AMN was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: AMN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMN were set to 27604308
Phenotypes for gene: AMN were set to Intrinsic factor receptor deficiency due to AMN mutations (Disorders of cobalamin absorption, transport and metabolism); Proteinuric renal disease; Unexplained kidney failure in young people
Likely inborn error of metabolism - targeted testing not possible v0.4 ALDOB Ellen McDonagh gene: ALDOB was added
gene: ALDOB was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: ALDOB was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALDOB were set to 27604308
Phenotypes for gene: ALDOB were set to hereditary fructose intolerance; Hereditary fructose intolerance (Disorders of fructose metabolism); acidosis with ketototic hypoglycaemia often hepatomegaly in acute presentation
Likely inborn error of metabolism - targeted testing not possible v0.4 ALDH18A1 Ellen McDonagh gene: ALDH18A1 was added
gene: ALDH18A1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: ALDH18A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALDH18A1 were set to 27604308; 24816252
Phenotypes for gene: ALDH18A1 were set to 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
Likely inborn error of metabolism - targeted testing not possible v0.4 AKR1D1 Ellen McDonagh gene: AKR1D1 was added
gene: AKR1D1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: AKR1D1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AKR1D1 were set to 27604308; 24816252
Phenotypes for gene: AKR1D1 were set to ?4-3-oxysterol 5?-reductase deficiency (Disorders of bile acid biosynthesis); Bile acid synthesis defect, congenital, 2 235555
Likely inborn error of metabolism - targeted testing not possible v0.4 AGPS Ellen McDonagh gene: AGPS was added
gene: AGPS was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: AGPS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGPS were set to 27604308
Phenotypes for gene: AGPS were set to Rhizomelic chondrodysplasia punctata, type 3 600121; Rhizomelic chondrodysplasia punctata type 3 (Peroxisomal disorders)
Likely inborn error of metabolism - targeted testing not possible v0.4 AGL Ellen McDonagh gene: AGL was added
gene: AGL was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: AGL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGL were set to 27604308
Phenotypes for gene: AGL were set to Glycogen storage disease type III, Cori (Glycogen storage disorders); Glycogen storage disease IIIb, 232400; Glycogen Storage Disorders- Liver; Glycogen Storage Disease; myopathy, cardiomyopathy and neuropathy possible but mile hepatomegaly and fasting intolerance; Glycogen Storage Disease Type III; Glycogen Storage Disorders- Muscle; Glycogen storage disease IIIa, 232400
Likely inborn error of metabolism - targeted testing not possible v0.4 AGK Ellen McDonagh Added phenotypes Disorders of mitochondrial membrane lipids (Mitochondrial respiratory chain disorders (caused by nuclear variants only)); Mitochondrial DNA depletion syndrome 10; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Acylglycerol kinase deficiency (Senger syndrome) (Disorders of complex lipid synthesis); Sengers syndrome, 212350; Sengers syndrome 212350; Disorders of mitochondrial lipid metabolism; Cataract 38, autosomal recessive, 614691 for gene: AGK
Publications for gene AGK were changed from to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 AGK Ellen McDonagh gene: AGK was added
gene: AGK was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: AGK was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: AGK were set to Cataract 38, autosomal recessive, 614691; Mitochondrial DNA depletion syndrome 10; Sengers syndrome, 212350; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Disorders of mitochondrial lipid metabolism
Likely inborn error of metabolism - targeted testing not possible v0.4 ADA Ellen McDonagh gene: ADA was added
gene: ADA was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: ADA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADA were set to 27604308
Phenotypes for gene: ADA were set to Combined B and T cell defect; Adenosine deaminase deficiency (Disorders of purine metabolism); SCID; Infantile enterocolitis & monogenic inflammatory bowel disease
Likely inborn error of metabolism - targeted testing not possible v0.4 ACAT1 Ellen McDonagh gene: ACAT1 was added
gene: ACAT1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: ACAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACAT1 were set to 27604308
Phenotypes for gene: ACAT1 were set to Cytosolic acetoacetyl-CoA thiolase deficiency (Disorders of ketone body metabolism); Fasting intolerance with acidosis, ? residual neurological problems; 3-Oxothiolase deficiency (Organic acidurias)
Likely inborn error of metabolism - targeted testing not possible v0.4 ABHD5 Ellen McDonagh gene: ABHD5 was added
gene: ABHD5 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: ABHD5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABHD5 were set to 27604308
Phenotypes for gene: ABHD5 were set to Chanarin-Dorfman syndrome 275630; Neutral lipid storage disease (Disorders of lipolysis)
Likely inborn error of metabolism - targeted testing not possible v0.4 ABHD12 Ellen McDonagh gene: ABHD12 was added
gene: ABHD12 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: ABHD12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABHD12 were set to 27604308
Phenotypes for gene: ABHD12 were set to Hereditary ataxia; Posterior segment abnormalities; Congenital hearing impairment (profound/severe); PHARC syndrome (Disorders of complex lipid synthesis)
Likely inborn error of metabolism - targeted testing not possible v0.4 ABCG8 Ellen McDonagh gene: ABCG8 was added
gene: ABCG8 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: ABCG8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCG8 were set to 27604308
Phenotypes for gene: ABCG8 were set to Sitosterolaemia (Inherited hypercholesterolaemias); Familial hypercholesterolaemia
Likely inborn error of metabolism - targeted testing not possible v0.4 ABCG5 Ellen McDonagh gene: ABCG5 was added
gene: ABCG5 was added to Inborn errors of metabolism. Sources: Expert Review Amber
Mode of inheritance for gene: ABCG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCG5 were set to 27604308
Phenotypes for gene: ABCG5 were set to Sitosterolaemia (Inherited hypercholesterolaemias); Familial hypercholesterolaemia
Likely inborn error of metabolism - targeted testing not possible v0.4 ABCB11 Ellen McDonagh gene: ABCB11 was added
gene: ABCB11 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: ABCB11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCB11 were set to 27604308
Phenotypes for gene: ABCB11 were set to Progressive familial intrahepatic cholestasis type 2 (Disorders of bile acid metabolism and transport); Cholestasis, benign recurrent intrahepatic, 2 605479; Cholestasis, progressive familial intrahepatic 2 601847
Likely inborn error of metabolism - targeted testing not possible v0.4 ABCA1 Ellen McDonagh gene: ABCA1 was added
gene: ABCA1 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: ABCA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABCA1 were set to 27604308
Phenotypes for gene: ABCA1 were set to Tangier disease (Disorders of high density lipoprotein metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 AASS Ellen McDonagh gene: AASS was added
gene: AASS was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: AASS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AASS were set to 27604308
Phenotypes for gene: AASS were set to Intellectual disability; Hyperlysinemia; Hyperlysinaemia (Disorders of histidine, tryptophan or lysine metabolism)
Likely inborn error of metabolism - targeted testing not possible v0.4 AARS2 Ellen McDonagh Added phenotypes Required for mitochondrial gene expression (Mitochondrial respiratory chain disorders (caused by nuclear variants only); Combined oxidative phosphorylation deficiency 8, 614096; Multiple respiratory chain complex deficiencies (disorders of protein synthesis); infantile mitochondrial cardiomyopathy for gene: AARS2
Publications for gene AARS2 were changed from 25058219; PMID: 21549344 to 27604308
Likely inborn error of metabolism - targeted testing not possible v0.4 AARS2 Ellen McDonagh gene: AARS2 was added
gene: AARS2 was added to Inborn errors of metabolism. Sources: Expert Review Green
Mode of inheritance for gene: AARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AARS2 were set to 25058219; PMID: 21549344
Phenotypes for gene: AARS2 were set to Multiple respiratory chain complex deficiencies (disorders of protein synthesis); Combined oxidative phosphorylation deficiency 8, 614096; infantile mitochondrial cardiomyopathy
Likely inborn error of metabolism - targeted testing not possible v0.1 Ellen McDonagh List of related panels changed from to Likely inborn error of metabolism - targeted testing not possible; GMS R98