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Optic neuropathy v4.30 BTD Achchuthan Shanmugasundram Phenotypes for gene: BTD were changed from Biotinidase deficiency, OMIM:253260 to Biotinidase deficiency, OMIM:253260; optic atrophy, MONDO:0003608
Optic neuropathy v4.29 BTD Achchuthan Shanmugasundram edited their review of gene: BTD: Changed phenotypes to: Biotinidase deficiency, OMIM:253260, optic atrophy, MONDO:0003608
Optic neuropathy v4.29 BTD Achchuthan Shanmugasundram Classified gene: BTD as Amber List (moderate evidence)
Optic neuropathy v4.29 BTD 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 review.
Optic neuropathy v4.29 BTD Achchuthan Shanmugasundram Gene: btd has been classified as Amber List (Moderate Evidence).
Optic neuropathy v4.28 BTD Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: BTD.
Optic neuropathy v4.28 BTD Achchuthan Shanmugasundram gene: BTD was added
gene: BTD was added to Optic neuropathy. Sources: Literature
Mode of inheritance for gene: BTD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BTD were set to 26203071; 29025919; 32235217; 33364171
Phenotypes for gene: BTD were set to Biotinidase deficiency, OMIM:253260
Review for gene: BTD was set to GREEN
Added comment: PMID:26203071 - A 22-year-old man presented with a disabling extensive myelopathy and bilateral optic neuropathy which mimicked the findings of a (seronegative) neuromyelitis optica. A novel homozygous BTD variant (p.Ala439Asp) and a known variant (c.1413T>C/ p.Cys471Cys) were identified in this patient.

PMID:29025919 - Two unrelated individuals with adult-onset biotinidase deficiency had severe, but reversible optic neuropathy. They were identified with compound heterozygous variants (patient 1: p.Phe232Cys/ p.Leu440Pro; patient 2: p.Gln456His/ p.Arg538Cys).

PMID:32235217 - A 49-year-old man was reported with progressive optic atrophy, peripheral neuropathy, and systemic weakness and fatigue due to biotinidase deficiency. This patient was reported with compound heterozygous variants (p.Ala171Thr/ p.Asp444His)

PMID:33364171 - Two adult brothers were reported with biallelic BTD variants. Both of them presented with lower limb neuropathy and one had progressive optic neuropathy.
Sources: Literature
Optic neuropathy v4.27 PDXK Achchuthan Shanmugasundram Classified gene: PDXK as Amber List (moderate evidence)
Optic neuropathy v4.27 PDXK Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (three unrelated cases and functional studies) for the promotion of this gene to green rating in the next GMS update.
Optic neuropathy v4.27 PDXK Achchuthan Shanmugasundram Gene: pdxk has been classified as Amber List (Moderate Evidence).
Optic neuropathy v4.26 PDXK Achchuthan Shanmugasundram Tag Q2_24_promote_green tag was added to gene: PDXK.
Optic neuropathy v4.26 PDXK Achchuthan Shanmugasundram gene: PDXK was added
gene: PDXK was added to Optic neuropathy. Sources: Literature
Mode of inheritance for gene: PDXK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDXK were set to 31187503; 32522499
Phenotypes for gene: PDXK were set to Neuropathy, hereditary motor and sensory, type VIC, with optic atrophy, OMIM:618511
Review for gene: PDXK was set to GREEN
Added comment: PMID:31187503 - Five individuals from two unrelated families were reported with biallelic PDXK variants and with primary axonal polyneuropathy and optic atrophy. This association was also supported by results from cell-based functional assays. The biochemical profile can be rescued with PLP supplementation associated with clinical improvement.

PMID:32522499 - Two affected siblings with a novel biallelic missense PDXK variant were reported with a similar phenotype as reported in PMID:31187503 with earlier onset. Functional analysis showed that this variant leads to almost complete loss of PDXK enzymatic activity and low PLP levels.

This gene has been associated with relevant phenotypes in OMIM (MIM #618511), but not yet in Gene2Phenotype.
Sources: Literature
Optic neuropathy v4.24 SNF8 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are two unrelated cases reported with optic atrophy and hence this gene should be rated amber with Current evidence.; to: Comment on list classification: There are two unrelated cases reported with optic atrophy and hence this gene should be rated amber with current evidence.
Optic neuropathy v4.24 SNF8 Achchuthan Shanmugasundram Classified gene: SNF8 as Amber List (moderate evidence)
Optic neuropathy v4.24 SNF8 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are two unrelated cases reported with optic atrophy and hence this gene should be rated amber with Current evidence.
Optic neuropathy v4.24 SNF8 Achchuthan Shanmugasundram Gene: snf8 has been classified as Amber List (Moderate Evidence).
Optic neuropathy v4.23 SNF8 Achchuthan Shanmugasundram gene: SNF8 was added
gene: SNF8 was added to Optic neuropathy. Sources: Literature
Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNF8 were set to 38423010
Phenotypes for gene: SNF8 were set to neurodevelopmental disorder, MONDO:0700092; optic atrophy, MONDO:0003608
Review for gene: SNF8 was set to AMBER
Added comment: PMID:38423010 reported nine individuals from six families presenting with a spectrum of neurodevelopmental/ neurodegenerative features caused by biallelic variants in SNF8.

The phenotypic spectrum included four individuals with severe developmental and epileptic encephalopathy with leukoencephalopathy and early death in three of those cases. Two individuals died too young to develop epilepsy. A second cohort shows a milder phenotype with intellectual disability, childhood-onset optic atrophy, or ataxia. All mildly affected individuals shared the same hypomorphic variant, c.304G>A (p.Val102Ile) as compound heterozygous. Three of the patients (from two families) with the milder phenotype also have optic atrophy.

Functional studies using fibroblasts derived from patients and zebrafish model showed loss of function as the disease mechanism.

This gene has not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Optic neuropathy v4.22 INTS8 Arina Puzriakova Phenotypes for gene: INTS8 were changed from Optic atrophy to ?Neurodevelopmental disorder with cerebellar hypoplasia and spasticity, OMIM:618572
Optic neuropathy v4.21 DNAJC30 Sarah Leigh Tag gene-checked was removed from gene: DNAJC30.
Optic neuropathy v4.21 DNAJC30 Sarah Leigh commented on gene: DNAJC30
Optic neuropathy v4.21 DNAJC30 Sarah Leigh Phenotypes for gene: DNAJC30 were changed from Leber hereditary optic neuropathy, MONDO:0010788 to Leber-like hereditary optic neuropathy, autosomal recessive 1, MONDO:0958183; Leber-like hereditary optic neuropathy, autosomal recessive 1, OMIM:619382
Optic neuropathy v4.20 DNAJC30 Sarah Leigh Publications for gene: DNAJC30 were set to 33465056; 35091433
Optic neuropathy v4.19 HSD17B10 Arina Puzriakova Publications for gene: HSD17B10 were set to 19706438; 22132097; 12696021; 26950678; 27604308; 12872843; 12555940
Optic neuropathy v4.18 HSD17B10 Arina Puzriakova Classified gene: HSD17B10 as Amber List (moderate evidence)
Optic neuropathy v4.18 HSD17B10 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update - optic nerve atrophy with visual loss can be a reported feature of HSD10 disease (PMIDs: 22132097; 26950678; 27295195)
Optic neuropathy v4.18 HSD17B10 Arina Puzriakova Gene: hsd17b10 has been classified as Amber List (Moderate Evidence).
Optic neuropathy v4.17 HSD17B10 Arina Puzriakova gene: HSD17B10 was added
gene: HSD17B10 was added to Optic neuropathy. Sources: Literature
Q1_24_promote_green tags were added to gene: HSD17B10.
Mode of inheritance for gene: HSD17B10 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: HSD17B10 were set to 19706438; 22132097; 12696021; 26950678; 27604308; 12872843; 12555940
Phenotypes for gene: HSD17B10 were set to HSD10 mitochondrial disease, OMIM:300438
Review for gene: HSD17B10 was set to GREEN
Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene for 2-methyl-3-hydroxybutyrylL-coA dehydrogenase deficiency and for intellectual development disorder syndromic X-linked type 10. Multiple unrelated individuals (at least 8 variants) with supportive functional studies reported in the literature, including some affected female carriers presenting with mild to moderate developmental delay or intellectual disability.
Phenotype in severely affected males comprises developmental regression in infancy or early childhood, often associated with early-onset intractable seizures, progressive choreoathetosis and spastic tetraplegia, optic atrophy or retinal degeneration resulting in visual loss, and mental retardation.
Sources: Literature
Optic neuropathy v4.16 MCAT Ivone Leong Phenotypes for gene: MCAT were changed from progressive autosomal recessive optic neuropathy to progressive autosomal recessive optic neuropathy; Hereditary optic neuropathy, MONDO:0020249
Optic neuropathy v4.15 MCAT Ivone Leong Publications for gene: MCAT were set to 31915829
Optic neuropathy v4.14 MCAT Ivone Leong Classified gene: MCAT as Amber List (moderate evidence)
Optic neuropathy v4.14 MCAT Ivone Leong Added comment: Comment on list classification: Promoted from Red to Amber, based on new evidence of a second case (PMID:33918393).
Optic neuropathy v4.14 MCAT Ivone Leong Gene: mcat has been classified as Amber List (Moderate Evidence).
Optic neuropathy v4.11 MT-ND6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND6.
Optic neuropathy v4.11 MT-ND4 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND4.
Optic neuropathy v4.11 MT-ND1 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ND1.
Optic neuropathy v4.11 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing was removed from gene: MT-ATP6.
Optic neuropathy v4.11 MT-ND6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing tag was added to gene: MT-ND6.
Optic neuropathy v4.11 MT-ND4 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing tag was added to gene: MT-ND4.
Optic neuropathy v4.11 MT-ND1 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing tag was added to gene: MT-ND1.
Optic neuropathy v4.11 MT-ATP6 Achchuthan Shanmugasundram Tag limit of detection for heteroplasmic variants is not validated for WGS testing tag was added to gene: MT-ATP6.
Optic neuropathy v4.11 ALPK1 Sarah Leigh reviewed gene: ALPK1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Optic neuropathy v4.11 ALPK1 Sarah Leigh Publications for gene: ALPK1 were set to 30967659; 31053777; 31939038; 34159509
Optic neuropathy v4.10 LETM1 Sarah Leigh changed review comment from: LETM1 variants has 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).; 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).
Optic neuropathy v4.10 HIKESHI Achchuthan Shanmugasundram Tag watchlist was removed from gene: HIKESHI.
Tag Q3_23_promote_green tag was added to gene: HIKESHI.
Tag Q3_23_NHS_review tag was added to gene: HIKESHI.
Optic neuropathy v4.10 HIKESHI Achchuthan Shanmugasundram Classified gene: HIKESHI as Amber List (moderate evidence)
Optic neuropathy v4.10 HIKESHI Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated cases) available now for promoting this gene to green rating at the next GMS review.
Optic neuropathy v4.10 HIKESHI Achchuthan Shanmugasundram Gene: hikeshi has been classified as Amber List (Moderate Evidence).
Optic neuropathy v4.9 HIKESHI Achchuthan Shanmugasundram Publications for gene: HIKESHI were set to 26545878; 28000699
Optic neuropathy v4.8 LETM1 Sarah Leigh Entity copied from Possible mitochondrial disorder - nuclear genes v3.41
Optic neuropathy v4.8 LETM1 Sarah Leigh gene: LETM1 was added
gene: LETM1 was added to Optic neuropathy. Sources: Expert Review,Expert Review Amber
Q3_23_promote_green, Q3_23_MOI tags were added to gene: LETM1.
Mode of inheritance for gene: LETM1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LETM1 were set to 36055214; 33815143
Phenotypes for gene: LETM1 were set to Neurodegeneration, childhood-onset, with multisystem involvement due to mitochondrial dysfunction, OMIM:620089
Optic neuropathy v4.7 MCAT Hannah Knight reviewed gene: MCAT: Rating: AMBER; Mode of pathogenicity: None; Publications: 33918393; Phenotypes: Hereditary optic neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v4.7 MCAT Hannah Knight Deleted their review
Optic neuropathy v4.7 MCAT Hannah Knight reviewed gene: MCAT: Rating: AMBER; Mode of pathogenicity: None; Publications: 33918393; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v4.7 LHX2 Sarah Leigh edited their review of gene: LHX2: Changed rating: GREEN
Optic neuropathy v4.7 LHX2 Sarah Leigh Classified gene: LHX2 as Amber List (moderate evidence)
Optic neuropathy v4.7 LHX2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Optic neuropathy v4.7 LHX2 Sarah Leigh Gene: lhx2 has been classified as Amber List (Moderate Evidence).
Optic neuropathy v4.6 LHX2 Sarah Leigh Tag Q3_23_promote_green tag was added to gene: LHX2.
Optic neuropathy v4.6 LHX2 Sarah Leigh changed review comment from: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 37057675 reports 17 predominantly de novo LHX2 variants in a panel of patients with a variable neurodevelopmental disorder. Haploinsufficiency and functional studies are supportive of a loss-of-function pathogenic action of the reported LHX2 variants.
Seven out of the ten cases reported in table 1 (PMID: 37057675) are listed as having microcephaly, however, due to lack of clinical information, these cases cannot be classified as severe (personal communication with the author, Christiane Zweier).
Sources: Literature; to: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. PMID: 37057675 reports 17 predominantly de novo LHX2 variants in a panel of patients with a variable neurodevelopmental disorder. Haploinsufficiency and functional studies are supportive of a loss-of-function pathogenic action of the reported LHX2 variants.
Nine out of the thirteen cases reported in table 1 (PMID: 37057675) are listed as having Ophthalmologic abnormalities including macular degeneration, optic neuropathy, and esotropia.
Sources: Literature
Optic neuropathy v4.6 LHX2 Sarah Leigh Entity copied from Severe microcephaly v4.28
Optic neuropathy v4.6 LHX2 Sarah Leigh gene: LHX2 was added
gene: LHX2 was added to Optic neuropathy. Sources: Expert Review Amber,Literature
Mode of inheritance for gene: LHX2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: LHX2 were set to 37057675
Phenotypes for gene: LHX2 were set to neurodevelopmental disorder
Optic neuropathy v4.5 HIKESHI Hannah Knight reviewed gene: HIKESHI: Rating: GREEN; Mode of pathogenicity: None; Publications: 34111619; Phenotypes: Leukodystrophy, hypomyelinating; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v4.5 UCHL1 Sarah Leigh Tag Q3_23_MOI tag was added to gene: UCHL1.
Optic neuropathy v4.5 UCHL1 Sarah Leigh reviewed gene: UCHL1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23359680, 28007905, 35986737; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic neuropathy v4.5 UCHL1 Sarah Leigh Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209; Spastic paraplegia 79A, autosomal dominant, OMIM:620221 to Spastic paraplegia 79B, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209; Spastic paraplegia 79A, autosomal dominant, OMIM:620221
Optic neuropathy v4.4 UCHL1 Sarah Leigh Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive, 615491 to Spastic paraplegia 79, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209; Spastic paraplegia 79A, autosomal dominant, OMIM:620221
Optic neuropathy v4.3 UCHL1 Sarah Leigh Publications for gene: UCHL1 were set to 29735986; 23359680; 28007905
Optic neuropathy v4.2 NDUFS1 Arina Puzriakova Phenotypes for gene: NDUFS1 were changed from MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 5, 618226 to Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226
Optic neuropathy v4.1 Achchuthan Shanmugasundram Panel version 4.0 has been signed off on 2023-03-22
Optic neuropathy v4.0 Achchuthan Shanmugasundram promoted panel to version 4.0
Optic neuropathy v3.12 OPA1 Achchuthan Shanmugasundram Publications for gene: OPA1 were set to 15531309; 16158427; 17306754; 18065439; 18158317; 19029523; 20417570; 20157015; 21636302; 25012220; 25146916
Optic neuropathy v3.11 MAG Arina Puzriakova Entity copied from Hereditary spastic paraplegia - childhood onset v3.18
Optic neuropathy v3.11 MAG Arina Puzriakova gene: MAG was added
gene: MAG was added to Optic neuropathy. Sources: Yorkshire and North East GLH,London North GLH,Literature,Expert Review Amber,NHS GMS
Q1_23_promote_green tags were added to gene: MAG.
Mode of inheritance for gene: MAG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAG were set to 24482476; 26179919; 31402626; 32629324; 32340215
Phenotypes for gene: MAG were set to Spastic paraplegia 75, autosomal recessive, OMIM:616680
Optic neuropathy v3.10 DNAJC30 Eleanor Williams Phenotypes for gene: DNAJC30 were changed from to Leber hereditary optic neuropathy, MONDO:0010788
Optic neuropathy v3.9 DNAJC30 Eleanor Williams Publications for gene: DNAJC30 were set to
Optic neuropathy v3.8 DNAJC30 Eleanor Williams Tag gene-checked tag was added to gene: DNAJC30.
Optic neuropathy v3.8 BLOC1S1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: BLOC1S1.
Optic neuropathy v3.8 SSBP1 Achchuthan Shanmugasundram Classified gene: SSBP1 as Green List (high evidence)
Optic neuropathy v3.8 SSBP1 Achchuthan Shanmugasundram Gene: ssbp1 has been classified as Green List (High Evidence).
Optic neuropathy v3.7 TFG Achchuthan Shanmugasundram Tag Q3_21_rating was removed from gene: TFG.
Optic neuropathy v3.7 SSBP1 Achchuthan Shanmugasundram Tag Q1_22_MOI was removed from gene: SSBP1.
Optic neuropathy v3.7 SPG7 Achchuthan Shanmugasundram Tag Q3_22_MOI was removed from gene: SPG7.
Tag Q3_22_NHS_review was removed from gene: SPG7.
Optic neuropathy v3.7 SLC44A1 Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: SLC44A1.
Optic neuropathy v3.7 OPA1 Achchuthan Shanmugasundram Tag Q2_22_MOI was removed from gene: OPA1.
Optic neuropathy v3.7 NDUFA12 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: NDUFA12.
Optic neuropathy v3.7 ISCA2 Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: ISCA2.
Optic neuropathy v3.7 EPRS Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: EPRS.
Optic neuropathy v3.7 C19orf12 Achchuthan Shanmugasundram Tag Q2_22_MOI was removed from gene: C19orf12.
Optic neuropathy v3.7 ATG7 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: ATG7.
Optic neuropathy v3.7 ACO2 Achchuthan Shanmugasundram Tag Q2_22_MOI was removed from gene: ACO2.
Tag Q2_22_NHS_review was removed from gene: ACO2.
Optic neuropathy v3.7 DNAJC30 Achchuthan Shanmugasundram reviewed gene: DNAJC30: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Optic neuropathy v3.7 TFG Achchuthan Shanmugasundram reviewed gene: TFG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Optic neuropathy v3.7 SSBP1 Achchuthan Shanmugasundram commented on gene: SSBP1
Optic neuropathy v3.7 SPG7 Achchuthan Shanmugasundram commented on gene: SPG7
Optic neuropathy v3.7 SLC44A1 Achchuthan Shanmugasundram reviewed gene: SLC44A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Optic neuropathy v3.7 OPA1 Achchuthan Shanmugasundram commented on gene: OPA1
Optic neuropathy v3.7 NDUFA12 Achchuthan Shanmugasundram reviewed gene: NDUFA12: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Optic neuropathy v3.7 ISCA2 Achchuthan Shanmugasundram reviewed gene: ISCA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Optic neuropathy v3.7 EPRS Achchuthan Shanmugasundram reviewed gene: EPRS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Optic neuropathy v3.7 C19orf12 Achchuthan Shanmugasundram commented on gene: C19orf12
Optic neuropathy v3.7 ATG7 Achchuthan Shanmugasundram reviewed gene: ATG7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Optic neuropathy v3.7 ACO2 Achchuthan Shanmugasundram commented on gene: ACO2
Optic neuropathy v3.6 TFG Achchuthan Shanmugasundram Source Expert Review Green was added to TFG.
Source NHS GMS was added to TFG.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v3.6 SSBP1 Achchuthan Shanmugasundram Source NHS GMS was added to SSBP1.
Mode of inheritance for gene SSBP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Green List (high evidence) to Red List (low evidence)
Optic neuropathy v3.6 SPG7 Achchuthan Shanmugasundram Source NHS GMS was added to SPG7.
Mode of inheritance for gene SPG7 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Optic neuropathy v3.6 SLC44A1 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC44A1.
Source NHS GMS was added to SLC44A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v3.6 OPA1 Achchuthan Shanmugasundram Source NHS GMS was added to OPA1.
Mode of inheritance for gene OPA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic neuropathy v3.6 NDUFA12 Achchuthan Shanmugasundram Source Expert Review Green was added to NDUFA12.
Source NHS GMS was added to NDUFA12.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v3.6 ISCA2 Achchuthan Shanmugasundram Source Expert Review Green was added to ISCA2.
Source NHS GMS was added to ISCA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v3.6 EPRS Achchuthan Shanmugasundram Source Expert Review Green was added to EPRS.
Source NHS GMS was added to EPRS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v3.6 DNAJC30 Achchuthan Shanmugasundram gene: DNAJC30 was added
gene: DNAJC30 was added to Optic neuropathy. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: DNAJC30 was set to BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v3.6 C19orf12 Achchuthan Shanmugasundram Source NHS GMS was added to C19orf12.
Mode of inheritance for gene C19orf12 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic neuropathy v3.6 ATG7 Achchuthan Shanmugasundram Source Expert Review Green was added to ATG7.
Source NHS GMS was added to ATG7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v3.6 ACO2 Achchuthan Shanmugasundram Source NHS GMS was added to ACO2.
Mode of inheritance for gene ACO2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic neuropathy v3.5 SLC52A2 Achchuthan Shanmugasundram Phenotypes for gene: SLC52A2 were changed from Brown-Vialetto-Van Laere syndrome 2, 614707 to Brown-Vialetto-Van Laere syndrome 2, MIM# 614707, MONDO:0013867; Optic atrophy, MONDO:0003608
Optic neuropathy v3.4 SLC52A2 Achchuthan Shanmugasundram Publications for gene: SLC52A2 were set to 23243084; 22864630
Optic neuropathy v3.3 SLC52A2 Achchuthan Shanmugasundram reviewed gene: SLC52A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22740598, 22864630, 23243084, 24253200, 30343981, 30377535, 31868069, 35608644, 36186484; Phenotypes: Brown-Vialetto-Van Laere syndrome 2, MIM# 614707, MONDO:0013867, Optic atrophy, MONDO:0003608; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v3.3 SLC25A46 Achchuthan Shanmugasundram Phenotypes for gene: SLC25A46 were changed from Neuropathy, hereditary motor and sensory, type VIB 616505 to Optic atrophy, MONDO:0003608; Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505; Pontocerebellar hypoplasia, type 1E, MIM# 619303, MONDO:0030260
Optic neuropathy v3.2 SLC25A46 Achchuthan Shanmugasundram Publications for gene: SLC25A46 were set to 26168012; 28369803
Optic neuropathy v3.1 SLC25A46 Achchuthan Shanmugasundram reviewed gene: SLC25A46: Rating: GREEN; Mode of pathogenicity: None; Publications: 26168012, 27430653, 28369803, 28376086, 28558379, 28934388, 30178502, 33816684; Phenotypes: Optic atrophy, MONDO:0003608, Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505, Pontocerebellar hypoplasia, type 1E, MIM# 619303, MONDO:0030260; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2022-11-30
Optic neuropathy v3.0 Arina Puzriakova promoted panel to version 3.0
Optic neuropathy v2.79 Arina Puzriakova List of related panels changed from Inherited optic neuropathies; R41; R42.2 to Inherited optic neuropathies; R41
Optic neuropathy v2.78 HK1 Arina Puzriakova Classified gene: HK1 as Amber List (moderate evidence)
Optic neuropathy v2.78 HK1 Arina Puzriakova Added comment: Comment on list classification: This gene should be promoted to Green at the next GMS panel update. Optic atrophy identified in 5/7 patients reported to date with HK1-related neurodevelopmental disorder (AD inheritance).
Optic neuropathy v2.78 HK1 Arina Puzriakova Gene: hk1 has been classified as Amber List (Moderate Evidence).
Optic neuropathy v2.77 HK1 Arina Puzriakova Added comment: Comment on mode of inheritance: Setting to 'monoallelic' as this is the appropriate MOI for this panel (MIM# 618547). Incorrect biallelic MOI was copied from ID panel which will be rectified following GMS approval (Q3_22).
Optic neuropathy v2.77 HK1 Arina Puzriakova Mode of inheritance for gene: HK1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Optic neuropathy v2.76 HK1 Arina Puzriakova Tag missense was removed from gene: HK1.
Tag Q3_22_MOI was removed from gene: HK1.
Tag Q3_22_NHS_review was removed from gene: HK1.
Tag Q4_22_promote_green tag was added to gene: HK1.
Optic neuropathy v2.76 HK1 Arina Puzriakova Entity copied from Intellectual disability v3.1756
Optic neuropathy v2.76 HK1 Arina Puzriakova gene: HK1 was added
gene: HK1 was added to Optic neuropathy. Sources: Expert Review Green,BRIDGE study SPEED NEURO Tier1 Gene
missense, Q3_22_MOI, Q3_22_NHS_review tags were added to gene: HK1.
Mode of inheritance for gene: HK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HK1 were set to 30778173; 28135719
Phenotypes for gene: HK1 were set to Neurodevelopmental disorder with visual defects and brain anomalies, OMIM:618547
Penetrance for gene: HK1 were set to Complete
Mode of pathogenicity for gene: HK1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Optic neuropathy v2.75 BLOC1S1 Arina Puzriakova Classified gene: BLOC1S1 as Amber List (moderate evidence)
Optic neuropathy v2.75 BLOC1S1 Arina Puzriakova Added comment: Comment on list classification: After seeking consultation from the Helen Brittain (Genomics England Clinical Team) due to the limited details provided in the paper as well as lack of additional support albeit with a sufficient number of total cases with a consistent phenotype (PMID:33875846), it was decided that the number of unrelated families presenting the relevant phenotype meets the criteria for an Amber rating at this time.
Optic neuropathy v2.75 BLOC1S1 Arina Puzriakova Gene: bloc1s1 has been classified as Amber List (Moderate Evidence).
Optic neuropathy v2.74 BLOC1S1 Arina Puzriakova Tag watchlist was removed from gene: BLOC1S1.
Optic neuropathy v2.74 BLOC1S1 Arina Puzriakova Entity copied from Intellectual disability v3.1700
Optic neuropathy v2.74 BLOC1S1 Arina Puzriakova gene: BLOC1S1 was added
gene: BLOC1S1 was added to Optic neuropathy. Sources: Literature
watchlist tags were added to gene: BLOC1S1.
Mode of inheritance for gene: BLOC1S1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BLOC1S1 were set to 33875846
Phenotypes for gene: BLOC1S1 were set to severe intellectual disability; severe global developmental delay; epilepsy
Penetrance for gene: BLOC1S1 were set to unknown
Optic neuropathy v2.73 NDUFA12 Arina Puzriakova Entity copied from Childhood onset dystonia or chorea or related movement disorder v1.251
Optic neuropathy v2.73 NDUFA12 Arina Puzriakova gene: NDUFA12 was added
gene: NDUFA12 was added to Optic neuropathy. Sources: Expert Review Amber,PanelApp,South West GLH
Q3_22_rating tags were added to gene: NDUFA12.
Mode of inheritance for gene: NDUFA12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFA12 were set to 21617257; 33715266; 35141356
Phenotypes for gene: NDUFA12 were set to Mitochondrial complex I deficiency, nuclear type 23, OMIM:618244
Optic neuropathy v2.72 SPG7 Ivone Leong edited their review of gene: SPG7: Added comment: Based on the expert review from Penny Clouston (Oxford) and recent literature the MOI should be changed from "BIALLELIC, autosomal or pseudoautosomal" to "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
Optic neuropathy v2.72 SPG7 Ivone Leong Tag Q3_21_MOI was removed from gene: SPG7.
Tag Q3_21_NHS_review was removed from gene: SPG7.
Tag Q3_22_MOI tag was added to gene: SPG7.
Tag Q3_22_NHS_review tag was added to gene: SPG7.
Optic neuropathy v2.72 SPG7 Ivone Leong Tag Q3_21_MOI tag was added to gene: SPG7.
Tag Q3_21_NHS_review tag was added to gene: SPG7.
Optic neuropathy v2.72 SPG7 Ivone Leong Phenotypes for gene: SPG7 were changed from SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE, 607259 to SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE, OMIM:607259; autosomal dominant optic atroph, MONDO:0020250
Optic neuropathy v2.71 SPG7 Ivone Leong Added comment: Comment on publications: New publications added
Optic neuropathy v2.71 SPG7 Ivone Leong Publications for gene: SPG7 were set to 9635427; 23065789; 22964162; 25034272
Optic neuropathy v2.70 SPG7 Penny Clouston reviewed gene: SPG7: Rating: GREEN; Mode of pathogenicity: None; Publications: 32548275, 33841295; Phenotypes: Dominnat optic atrophy; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal; Current diagnostic: yes
Optic neuropathy v2.70 ATG7 Arina Puzriakova Entity copied from Ataxia and cerebellar anomalies - narrow panel v2.298
Optic neuropathy v2.70 ATG7 Arina Puzriakova gene: ATG7 was added
gene: ATG7 was added to Optic neuropathy. Sources: Literature,Expert Review Amber
Q3_22_rating tags were added to gene: ATG7.
Mode of inheritance for gene: ATG7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATG7 were set to 34161705
Phenotypes for gene: ATG7 were set to Spinocerebellar ataxia, autosomal recessive 31, OMIM:619422
Optic neuropathy v2.69 ACO2 Sarah Leigh changed review comment from: PMID: 34056600 reports 61 cases of genetically unsolved inherited optic neuropathies who were harbouring variants in ACO2, of which 50 carried dominant variants. The authors state that this is the first report of monoallelic pathogenic ACO2 variants resulting in dominant optic atrophy.; to: PMID: 34056600 reports 61 cases of genetically unsolved inherited optic neuropathies who were harbouring variants in ACO2, of which 50 carried dominant variants (the remaining 11 cases were biallelic). The authors state that this is the first report of monoallelic pathogenic ACO2 variants resulting in dominant optic atrophy.
Optic neuropathy v2.69 ACO2 Sarah Leigh reviewed gene: ACO2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic neuropathy v2.69 ACO2 Sarah Leigh Tag Q2_22_MOI tag was added to gene: ACO2.
Tag Q2_22_NHS_review tag was added to gene: ACO2.
Optic neuropathy v2.69 ACO2 Sarah Leigh Publications for gene: ACO2 were set to 25351951; 22405087
Optic neuropathy v2.68 MT-ND4 Eleanor Williams Tag gene-checked tag was added to gene: MT-ND4.
Optic neuropathy v2.68 MT-ND1 Eleanor Williams Tag gene-checked tag was added to gene: MT-ND1.
Optic neuropathy v2.68 MT-ATP6 Eleanor Williams Tag gene-checked tag was added to gene: MT-ATP6.
Optic neuropathy v2.68 MT-ND6 Arina Puzriakova Tag gene-checked tag was added to gene: MT-ND6.
Optic neuropathy v2.68 AFG3L2 Arina Puzriakova Phenotypes for gene: AFG3L2 were changed from Optic atrophy 12, 618977 to Optic atrophy 12, OMIM:618977 (AD); Spastic ataxia 5, autosomal recessive, OMIM:614487 (AR)
Optic neuropathy v2.67 OPA1 Arina Puzriakova Publications for gene: OPA1 were set to
Optic neuropathy v2.66 OPA1 Arina Puzriakova Added comment: Comment on mode of inheritance: Should be updated from 'monoallelic' only to 'both mono- and biallelic' at the next GMS panel update. Biallelic variants cause Behr syndrome (MIM# 210000) in which early-onset optic atrophy is a main clinical feature of the phenotype (PMID: 20157015; 21636302; 25012220; 25146916). Sufficient cases have been reported to rate as green for both inheritance patterns.
Optic neuropathy v2.66 OPA1 Arina Puzriakova Mode of inheritance for gene: OPA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Optic neuropathy v2.65 OPA1 Arina Puzriakova Phenotypes for gene: OPA1 were changed from Optic atrophy 1, OMIM:165500; Optic atrophy plus syndrome, OMIM:125250; Behr syndrome, OMIM:210000 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
Optic neuropathy v2.64 OPA1 Arina Puzriakova Phenotypes for gene: OPA1 were changed from Optic atrophy 1 165500; Optic atrophy plus syndrome 125250 to Optic atrophy 1, OMIM:165500; Optic atrophy plus syndrome, OMIM:125250; Behr syndrome, OMIM:210000
Optic neuropathy v2.63 OPA1 Arina Puzriakova Tag Q2_22_MOI tag was added to gene: OPA1.
Optic neuropathy v2.63 MFN2 Arina Puzriakova Phenotypes for gene: MFN2 were changed from Optic Atrophy; Hereditary motor and sensory neuropathy VIA; Charcot-Marie-Tooth disease, axonal, type 2A2A (AD), 609260; Charcot-Marie-Tooth disease, axonal, type 2A2B (AR), 617087; Hereditary motor and sensory neuropathy VIA (AD), 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
Optic neuropathy v2.62 C19orf12 Sarah Leigh Tag Q2_22_MOI tag was added to gene: C19orf12.
Optic neuropathy v2.62 C19orf12 Sarah Leigh reviewed gene: C19orf12: Rating: ; Mode of pathogenicity: None; Publications: 29295770, 31087512; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic neuropathy v2.62 C19orf12 Sarah Leigh Phenotypes for gene: C19orf12 were changed from SPASTIC PARAPLEGIA 43, AUTOSOMAL RECESSIVE, 615043; NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 4, 614298 to ?Spastic paraplegia 43, autosomal recessive, OMIM:615043; Neurodegeneration with brain iron accumulation 4, OMIM: 614298
Optic neuropathy v2.61 C19orf12 Sarah Leigh Publications for gene: C19orf12 were set to 27772766; 26187298; 24209434; 22584950
Optic neuropathy v2.60 ALPK1 Ivone Leong Tag Q4_21_rating was removed from gene: ALPK1.
Tag Q4_21_NHS_review was removed from gene: ALPK1.
Optic neuropathy v2.60 ALPK1 Ivone Leong commented on gene: ALPK1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Optic neuropathy v2.59 ALPK1 Ivone Leong Source Expert Review Green was added to ALPK1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v2.58 UCHL1 Ivone Leong Tag for-review was removed from gene: UCHL1.
Optic neuropathy v2.58 NBAS Ivone Leong Tag for-review was removed from gene: NBAS.
Optic neuropathy v2.58 MECR Ivone Leong Tag for-review was removed from gene: MECR.
Optic neuropathy v2.58 FDXR Ivone Leong Tag for-review was removed from gene: FDXR.
Optic neuropathy v2.58 AFG3L2 Ivone Leong Tag for-review was removed from gene: AFG3L2.
Optic neuropathy v2.58 UCHL1 Ivone Leong commented on gene: UCHL1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Optic neuropathy v2.58 NBAS Ivone Leong commented on gene: NBAS: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Optic neuropathy v2.58 MECR Ivone Leong commented on gene: MECR: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Optic neuropathy v2.58 FDXR Ivone Leong commented on gene: FDXR: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Optic neuropathy v2.58 AFG3L2 Ivone Leong commented on gene: AFG3L2: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Optic neuropathy v2.57 UCHL1 Ivone Leong Source Expert Review Green was added to UCHL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v2.57 NBAS Ivone Leong Source Expert Review Green was added to NBAS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v2.57 MECR Ivone Leong Source Expert Review Green was added to MECR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v2.57 FDXR Ivone Leong Source Expert Review Green was added to FDXR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v2.57 AFG3L2 Ivone Leong Source Expert Review Green was added to AFG3L2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v2.56 ACO2 Tom Cullup edited their review of gene: ACO2: Added comment: New paper (34056600) describing ACO2 as a cause of autosomal dominant optic atrophy - update of inheritance needed.; Changed publications to: 25351951, 22405087, 34056600; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Set current diagnostic: yes
Optic neuropathy v2.56 SSBP1 Sarah Leigh changed review comment from: 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: 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).
Optic neuropathy v2.56 SSBP1 Sarah Leigh reviewed gene: SSBP1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic neuropathy v2.56 SSBP1 Sarah Leigh Tag Q1_22_MOI tag was added to gene: SSBP1.
Optic neuropathy v2.56 SSBP1 Sarah Leigh Phenotypes for gene: SSBP1 were changed from Optic atrophy 13 with retinal and foveal abnormalities, OMIM:165510; Autosomal dominant optic atrophy with variable retinal degeneration; Optic atrophy with retinal degeneration (+-systemic features) to Optic atrophy 13 with retinal and foveal abnormalities OMIM:165510
Optic neuropathy v2.55 SSBP1 Sarah Leigh Publications for gene: SSBP1 were set to 31298765; 31550240; 31550237; 30412255
Optic neuropathy v2.54 ALPK1 Ivone Leong Phenotypes for gene: ALPK1 were changed from Retinopathy; Optic disc swelling; Splenomegaly; Pancytopenia; Headaches; ocular inflammation. to ROSAH syndrome, OMIM:614979
Optic neuropathy v2.53 ALPK1 Ivone Leong Classified gene: ALPK1 as Amber List (moderate evidence)
Optic neuropathy v2.53 ALPK1 Ivone Leong Added comment: Comment on list classification: New gene added by Neringa Jurkute (MD). This gene is associated with a phenotype in OMIM and Gene2Phenotype (Strong). There is enough evidence to support a gene-disease assocation. This gene should be rated Green at the next review.
Optic neuropathy v2.53 ALPK1 Ivone Leong Gene: alpk1 has been classified as Amber List (Moderate Evidence).
Optic neuropathy v2.52 ALPK1 Ivone Leong Tag Q4_21_rating tag was added to gene: ALPK1.
Tag Q4_21_NHS_review tag was added to gene: ALPK1.
Optic neuropathy v2.52 ALPK1 Ivone Leong Publications for gene: ALPK1 were set to PMID: 30967659; 31053777; 31939038; 34159509
Optic neuropathy v2.51 ALPK1 Neringa Jurkute changed review comment from: Recurrent variant has been reported in affected individuals from 9 unrelated families. Affected individual shared overlapping phenotype with retinal dystrophy, chronic disc swelling observed in majority of cases.
Sources: Literature, Research, Other; to: Recurrent variant has been reported in affected individuals from 9 unrelated families. Affected individuals shared overlapping phenotype with retinal changes, chronic disc swelling observed in majority of cases.

OMIM: 614979
PMID: 30967659; 31053777; 31939038; 34159509
Sources: Literature, Research, Other
Optic neuropathy v2.51 ALPK1 Neringa Jurkute changed review comment from: Recurrent variant has been reported in affected individuals from 9 unrelated families. Affected individual shared overlapping phenotype with retinal dystrophy, chronic disc swelling observed in majority of cases.
Sources: Literature, Research, Other; to: Recurrent variant has been reported in affected individuals from 9 unrelated families. Affected individual shared overlapping phenotype with retinal dystrophy, chronic disc swelling observed in majority of cases.
Sources: Literature, Research, Other
Optic neuropathy v2.51 ALPK1 Neringa Jurkute gene: ALPK1 was added
gene: ALPK1 was added to Optic neuropathy. Sources: Literature,Research,Other
Mode of inheritance for gene: ALPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALPK1 were set to PMID: 30967659; 31053777; 31939038; 34159509
Phenotypes for gene: ALPK1 were set to Retinopathy; Optic disc swelling; Splenomegaly; Pancytopenia; Headaches; ocular inflammation.
Mode of pathogenicity for gene: ALPK1 was set to Other
Review for gene: ALPK1 was set to GREEN
Added comment: Recurrent variant has been reported in affected individuals from 9 unrelated families. Affected individual shared overlapping phenotype with retinal dystrophy, chronic disc swelling observed in majority of cases.
Sources: Literature, Research, Other
Optic neuropathy v2.51 FXN Arina Puzriakova Phenotypes for gene: FXN were changed from Friedreich ataxia (FRDA), 229300 to Friedreich ataxia, OMIM:229300; Friedreich ataxia with retained reflexes, OMIM:229300
Optic neuropathy v2.50 FXN Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: FXN.
Optic neuropathy v2.50 C12orf65 Arina Puzriakova Phenotypes for gene: C12orf65 were changed from SPASTIC PARAPLEGIA 55, AUTOSOMAL RECESSIVE, 615035 to Combined oxidative phosphorylation deficiency 7, OMIM:613559; Spastic paraplegia 55, autosomal recessive, OMIM:615035
Optic neuropathy v2.49 C12orf65 Arina Puzriakova Publications for gene: C12orf65 were set to 28091420; 25995486; 23188110; 24198383; 24284555; 24424123
Optic neuropathy v2.48 TFG Arina Puzriakova Classified gene: TFG as Amber List (moderate evidence)
Optic neuropathy v2.48 TFG Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.
Optic neuropathy v2.48 TFG Arina Puzriakova Gene: tfg has been classified as Amber List (Moderate Evidence).
Optic neuropathy v2.47 TFG Arina Puzriakova gene: TFG was added
gene: TFG was added to Optic neuropathy. Sources: Literature
Q3_21_rating tags were added to gene: TFG.
Mode of inheritance for gene: TFG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TFG were set to 23479643; 27492651; 29971521; 30467354
Phenotypes for gene: TFG were set to Spastic paraplegia 57, autosomal recessive, OMIM:615658
Review for gene: TFG was set to GREEN
Added comment: Biallelic variants cause a HSP (MIM# 615658) which has been shown to involve early-onset optic atrophy in complex cases. At least 4 unrelated families reported with optic atrophy and variants in this gene (PMIDs: 23479643; 27492651; 29971521; 30467354).

Note that monoallelic variants are associated with different phenotype comprising adult-onset neuropathy (MIM# 604484)
Sources: Literature
Optic neuropathy v2.46 ATAD3A Arina Puzriakova Phenotypes for gene: ATAD3A were changed from Harel-Yoon syndrome: optic atrophy, peripheral neuropathy, delayed psychomotor development, intellectual disability, spastic paraplegia (HAYOS), 617183 to Harel-Yoon syndrome, OMIM:617183
Optic neuropathy v2.45 EPRS Ivone Leong reviewed gene: EPRS: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Optic neuropathy v2.45 EPRS Ivone Leong Entity copied from White matter disorders and cerebral calcification - narrow panel v1.183
Optic neuropathy v2.45 EPRS Ivone Leong gene: EPRS was added
gene: EPRS was added to Optic neuropathy. Sources: Expert Review Amber,Expert list
new-gene-name, Q2_21_rating tags were added to gene: EPRS.
Mode of inheritance for gene: EPRS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EPRS were set to 29576217; 33805425
Phenotypes for gene: EPRS were set to Leukodystrophy, hypomyelinating, 15, MIM# 617951
Optic neuropathy v2.44 ZPR1 Ivone Leong Entity copied from Growth failure in early childhood v1.70
Optic neuropathy v2.44 ZPR1 Ivone Leong gene: ZPR1 was added
gene: ZPR1 was added to Optic neuropathy. Sources: Expert Review Red,Literature
founder-effect tags were added to gene: ZPR1.
Mode of inheritance for gene: ZPR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZPR1 were set to 29851065
Phenotypes for gene: ZPR1 were set to ?Growth restriction, hypoplastic kidneys, alopecia, and distinctive facies, OMIM:619321
Optic neuropathy v2.43 ISCA2 Ivone Leong Classified gene: ISCA2 as Amber List (moderate evidence)
Optic neuropathy v2.43 ISCA2 Ivone Leong Gene: isca2 has been classified as Amber List (Moderate Evidence).
Optic neuropathy v2.42 ISCA2 Ivone Leong gene: ISCA2 was added
gene: ISCA2 was added to Optic neuropathy. Sources: Literature
Q2_21_rating tags were added to gene: ISCA2.
Mode of inheritance for gene: ISCA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ISCA2 were set to 25539947; 29297947; 29122497; 29359243
Phenotypes for gene: ISCA2 were set to Multiple mitochondrial dysfunctions syndrome 4, OMIM:616370; optic atrophy, MONDO:0003608
Review for gene: ISCA2 was set to GREEN
Added comment: This gene is associated with a phenotype in OMIM but not Gene2Phenotype. There are >3 unrelated cases. Patients usually present with a triad of neurodevelopmental regression, nystagmus with optic atrophy, and diffuse white matter disease. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Sources: Literature
Optic neuropathy v2.41 HIKESHI Ivone Leong changed review comment from: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM but not in Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.; to: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM but not in Gene2Phenotype. There is currently not enough evidence to support a gene-disease association (only 2 cases with optic atrophy), therefore this gene has been given an Amber rating.
Optic neuropathy v2.41 HIKESHI Ivone Leong Tag watchlist tag was added to gene: HIKESHI.
Optic neuropathy v2.41 HIKESHI Ivone Leong Entity copied from White matter disorders and cerebral calcification - narrow panel v1.119
Optic neuropathy v2.41 HIKESHI Ivone Leong gene: HIKESHI was added
gene: HIKESHI was added to Optic neuropathy. Sources: Expert list,Expert Review Amber
Mode of inheritance for gene: HIKESHI was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HIKESHI were set to 26545878; 28000699
Phenotypes for gene: HIKESHI were set to Leukodystrophy, hypomyelinating, 13, OMIM:616881
Optic neuropathy v2.40 WFS1 Eleanor Williams Phenotypes for gene: WFS1 were changed from Wolfram syndrome to Wolfram syndrome 1, OMIM:222300
Optic neuropathy v2.39 WFS1 Eleanor Williams Publications for gene: WFS1 were set to
Optic neuropathy v2.38 WFS1 Eleanor Williams reviewed gene: WFS1: Rating: ; Mode of pathogenicity: None; Publications: 33693650; Phenotypes: ; Mode of inheritance: None
Optic neuropathy v2.38 ACO2 Arina Puzriakova Phenotypes for gene: ACO2 were changed from Optic atrophy 9; 616289; optic atrophy, nystagmus; Infantile cerebellar-retinal degeneration to Infantile cerebellar-retinal degeneration, OMIM:614559; Infantile cerebellar-retinal degeneration, MONDO:0013802; ?Optic atrophy 9, OMIM:616289; Optic atrophy 9, MONDO:0014571
Optic neuropathy v2.37 SLC44A1 Arina Puzriakova Classified gene: SLC44A1 as Amber List (moderate evidence)
Optic neuropathy v2.37 SLC44A1 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to rate this gene Green at the next GMS panel update - at least 3 unrelated families reported with distinct SLC44A1 variants and this neurodegenerative disorder, including optic nerve atrophy (PMID: 31855247).
Optic neuropathy v2.37 SLC44A1 Arina Puzriakova Gene: slc44a1 has been classified as Amber List (Moderate Evidence).
Optic neuropathy v2.36 SLC44A1 Arina Puzriakova gene: SLC44A1 was added
gene: SLC44A1 was added to Optic neuropathy. Sources: Literature
Q2_21_rating tags were added to gene: SLC44A1.
Mode of inheritance for gene: SLC44A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC44A1 were set to 31855247
Phenotypes for gene: SLC44A1 were set to Neurodegeneration, childhood-onset, with ataxia, tremor, optic atrophy, and cognitive decline, OMIM:618868; Neurodegeneration, childhood-onset, with ataxia, tremor, optic atrophy, and cognitive decline, MONDO:0030028
Review for gene: SLC44A1 was set to GREEN
Added comment: Associated with relevant phenotype in OMIM (MIM# 618868), but not yet in Gene2Phenotype.

- PMID: 31855247 (2020) - Four individuals from three families with different homozygous frameshift variants (Asp517Metfs*19, Ser126Metfs*8, and Lys90Metfs*18) in SLC44A1. Clinical features in all affected individuals included progressive ataxia, tremor, cognitive decline, bilateral optic nerve atrophy, dysarthria, as well as urinary and bowel incontinence. Brain MRI demonstrated cerebellar atrophy and leukoencephalopathy. Functional studies indicate choline transporter deficiency as the underlying pathological mechanism.
Sources: Literature
Optic neuropathy v2.35 OPA8 Arina Puzriakova Tag curated_removed tag was added to gene: OPA8.
Optic neuropathy v2.35 OPA6 Arina Puzriakova Tag curated_removed tag was added to gene: OPA6.
Optic neuropathy v2.35 OPA5 Arina Puzriakova Tag curated_removed tag was added to gene: OPA5.
Optic neuropathy v2.35 OPA4 Arina Puzriakova Tag curated_removed tag was added to gene: OPA4.
Optic neuropathy v2.35 OPA2 Arina Puzriakova Tag curated_removed tag was added to gene: OPA2.
Optic neuropathy v2.35 C12orf65 Catherine Snow Tag new-gene-name tag was added to gene: C12orf65.
Optic neuropathy v2.35 C12orf65 Catherine Snow commented on gene: C12orf65
Optic neuropathy v2.35 PDSS1 Ivone Leong Tag watchlist tag was added to gene: PDSS1.
Optic neuropathy v2.35 PDSS1 Ivone Leong Classified gene: PDSS1 as Amber List (moderate evidence)
Optic neuropathy v2.35 PDSS1 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM and Gene2Phenotype. As there are only 2 cases there is not enough evidence to support a gene-disease association. Therefore, this gene has been given an Amber rating.
Optic neuropathy v2.35 PDSS1 Ivone Leong Gene: pdss1 has been classified as Amber List (Moderate Evidence).
Optic neuropathy v2.34 PDSS1 Ivone Leong Publications for gene: PDSS1 were set to 33285023
Optic neuropathy v2.33 PDSS1 Ivone Leong Phenotypes for gene: PDSS1 were changed from Coenzyme Q10 deficiency, primary, 2, MIM# 614651 to Coenzyme Q10 deficiency, primary, 2, OMIM:614651
Optic neuropathy v2.32 SSBP1 Ivone Leong Phenotypes for gene: SSBP1 were changed from Autosomal dominant optic atrophy with variable retinal degeneration to Optic atrophy 13 with retinal and foveal abnormalities, OMIM:165510; Autosomal dominant optic atrophy with variable retinal degeneration; Optic atrophy with retinal degeneration (+-systemic features)
Optic neuropathy v2.31 SSBP1 Ivone Leong Publications for gene: SSBP1 were set to 31298765
Optic neuropathy v2.30 FDXR Ivone Leong Publications for gene: FDXR were set to 30250212; 28965846; 29040572; 32499495
Optic neuropathy v2.29 FDXR Neringa Jurkute reviewed gene: FDXR: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 28965846, 32499495, 30250212, 33348459, 29040572; Phenotypes: Optic atrophy and sensorineural hearing loss, mitochondrial disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v2.29 SSBP1 Neringa Jurkute reviewed gene: SSBP1: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 31298765, PMID: 31550240, PMID: 31550237, PMID: 30412255; Phenotypes: Optic atrophy with retinal degeneration (+-systemic features); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Optic neuropathy v2.29 PDSS1 Zornitza Stark gene: PDSS1 was added
gene: PDSS1 was added to Optic neuropathy. Sources: Literature
Mode of inheritance for gene: PDSS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDSS1 were set to 33285023
Phenotypes for gene: PDSS1 were set to Coenzyme Q10 deficiency, primary, 2, MIM# 614651
Review for gene: PDSS1 was set to AMBER
Added comment: Two families reported where optic atrophy and deafness are part of the phenotype.
Sources: Literature
Optic neuropathy v2.29 AP3B2 Ivone Leong Phenotypes for gene: AP3B2 were changed from Epileptic encephalopathy, early infantile, 48, 617276 to Developmental and epileptic encephalopathy 48, OMIM:617276, MONDO:0015000
Optic neuropathy v2.28 AP3B2 Ivone Leong Tag for-review was removed from gene: AP3B2.
Tag watchlist tag was added to gene: AP3B2.
Optic neuropathy v2.28 AP3B2 Ivone Leong changed review comment from: Comment on list classification: New gene added by Zornitza Stark. AP3B2 is associated with a relevant disease in OMIM and probably associated with a relevant disease in Gene2Phenotype. There is enough evidence for this gene to be Green; however, until the next major review this gene will be rated as Amber for now.; to: Comment on list classification: New gene added by Zornitza Stark. AP3B2 is associated with a relevant disease in OMIM and probably associated with a relevant disease in Gene2Phenotype. PMID:27889060 describes 2 out of 8 families where individuals who have variants in this gene had optic disc/nerve pallor. Therefore, there is currently not enough evidence to support a gene-disease association. Therefore, this gene has been given an Amber rating.
Optic neuropathy v2.28 INTS8 Ivone Leong gene: INTS8 was added
gene: INTS8 was added to Optic neuropathy. Sources: Literature
Mode of inheritance for gene: INTS8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS8 were set to 28542170
Phenotypes for gene: INTS8 were set to Optic atrophy
Review for gene: INTS8 was set to RED
Added comment: PMID: 28542170 describes one Dutch family with 3 affected siblings. All three are compound heterozygous for variants in this gene. Optic atrophy was listed as a phenotype for 2/3 siblings.
Sources: Literature
Optic neuropathy v2.27 AFG3L2 Ivone Leong reviewed gene: AFG3L2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Optic neuropathy v2.27 AFG3L2 Ivone Leong Tag for-review tag was added to gene: AFG3L2.
Optic neuropathy v2.27 AFG3L2 Ivone Leong Publications for gene: AFG3L2 were set to 29181157; 26539208; 30544562; 30252181; 30389403; 30252181; 30389403; 32219868
Optic neuropathy v2.26 AFG3L2 Ivone Leong Publications for gene: AFG3L2 were set to 29181157; 26539208; 30544562; 30252181; 30389403; 30252181; 30389403
Optic neuropathy v2.25 AFG3L2 Ivone Leong Phenotypes for gene: AFG3L2 were changed from Spastic ataxia 5, autosomal recessive, 614487; Spinocerebellar ataxia 28, 610246 to Optic atrophy 12, 618977
Optic neuropathy v2.24 ATAD3A Ivone Leong Tag watchlist tag was added to gene: ATAD3A.
Optic neuropathy v2.24 ATAD3A Ivone Leong Classified gene: ATAD3A as Amber List (moderate evidence)
Optic neuropathy v2.24 ATAD3A Ivone Leong Added comment: Comment on list classification: Promoted gene from Red to Amber based on the available literature. As not every patient with a monoallelic variant in this gene presented with optic atrophy, this gene has been rated Amber until further evidence is available.

PMID: 27640307 describes 5 patients from 5 unrelated families with the same de novo variant (c.1582 C>T, R528W). 3/5 patients have optic atrophy and 2/5 have hypertrophic cardiomyopathy (HCM). The authors have suggested that R528W exerts a dominant negative effect.

Three patients from 2 additional families have biallelic variants (1 compound heterozygous and 1 biallelic deletion of ATAD3B and ATAD3A). These 3 patients did not have optic atrophy nor HCM, but had congenital cataracts.

PMID: 28158749 describes a family with monoallelic variant (c.1064 G>A, G355D) where affected mother and son do not have optic atrophy nor HCM but have hereditary spastic paraplegia.

PMID: 31727539 describes a consanguineous family with 4 affected individuals with biallelic variant (c.1217T>G, L406R). 3/4 had congenital cataracts and 4/4 had HCM. No one had optic atrophy.
Optic neuropathy v2.24 ATAD3A Ivone Leong Gene: atad3a has been classified as Amber List (Moderate Evidence).
Optic neuropathy v2.23 ATAD3A Ivone Leong Publications for gene: ATAD3A were set to 27640307; 28652416
Optic neuropathy v2.22 AFG3L2 Ivone Leong Phenotypes for gene: AFG3L2 were changed from SPASTIC ATAXIA 5, AUTOSOMAL RECESSIVE, 614487; SPINOCEREBELLAR ATAXIA 28, 610246 to Spastic ataxia 5, autosomal recessive, 614487; Spinocerebellar ataxia 28, 610246
Optic neuropathy v2.21 AFG3L2 Ivone Leong Publications for gene: AFG3L2 were set to 29181157; 26539208; 30544562
Optic neuropathy v2.20 AP3B2 Ivone Leong Classified gene: AP3B2 as Amber List (moderate evidence)
Optic neuropathy v2.20 AP3B2 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark. AP3B2 is associated with a relevant disease in OMIM and probably associated with a relevant disease in Gene2Phenotype. There is enough evidence for this gene to be Green; however, until the next major review this gene will be rated as Amber for now.
Optic neuropathy v2.20 AP3B2 Ivone Leong Gene: ap3b2 has been classified as Amber List (Moderate Evidence).
Optic neuropathy v2.19 AP3B2 Ivone Leong Tag for-review tag was added to gene: AP3B2.
Optic neuropathy v2.19 AP3B2 Ivone Leong Phenotypes for gene: AP3B2 were changed from Early-onset epileptic encephalopathy with optic atrophy, MIM#617276 to Epileptic encephalopathy, early infantile, 48, 617276
Optic neuropathy v2.18 ATAD3A Ivone Leong Added comment: Comment on mode of inheritance: Changed MOI from Both monoallelic and biallelic to Monoallelic only as it is patients with the Monoallelic form had optic atrophy (PMID: 27640307). Patients with biallelic variants had congenital cataract.
Optic neuropathy v2.18 ATAD3A Ivone Leong Mode of inheritance for gene: ATAD3A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Optic neuropathy v2.17 ATAD3A Ivone Leong Publications for gene: ATAD3A were set to 27640307
Optic neuropathy v2.16 FDXR Ivone Leong Classified gene: FDXR as Amber List (moderate evidence)
Optic neuropathy v2.16 FDXR Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark.

This gene is associated with a relevant disease in OMIM. PMID: 2499495 describes a FDXR KO mouse model that had progressive optic neuropathy. Based on all the available evidence there is enough evidence to promote this gene to Green status, which will be done at the next major review. Therefore, this gene has been rated as Amber for now.
Optic neuropathy v2.16 FDXR Ivone Leong Gene: fdxr has been classified as Amber List (Moderate Evidence).
Optic neuropathy v2.15 FDXR Ivone Leong Tag for-review tag was added to gene: FDXR.
Optic neuropathy v2.15 FDXR Ivone Leong Publications for gene: FDXR were set to 30250212; 28965846; 29040572
Optic neuropathy v2.14 MCAT Ivone Leong Classified gene: MCAT as Red List (low evidence)
Optic neuropathy v2.14 MCAT Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark. Based on the evidence this gene has been rated as Red as there is only 1 reported case.
Optic neuropathy v2.14 MCAT Ivone Leong Gene: mcat has been classified as Red List (Low Evidence).
Optic neuropathy v2.13 FDXR Ivone Leong Phenotypes for gene: FDXR were changed from Auditory neuropathy and optic atrophy, MIM#617717 to Auditory neuropathy and optic atrophy, 617717
Optic neuropathy v2.12 FDXR Ivone Leong Publications for gene: FDXR were set to 30250212; 28965846
Optic neuropathy v2.11 MECR Ivone Leong Classified gene: MECR as Amber List (moderate evidence)
Optic neuropathy v2.11 MECR Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark and an additional Green review from Sara Martins. MECR is associated with a relevant phenotype in OMIM and probably associated with a relevant phenotype in Gene2Phenotype. There is enough evidence for this gene to be Green. Currently, it is rated Amber and will be promoted to Green status at the next major review.
Optic neuropathy v2.11 MECR Ivone Leong Gene: mecr has been classified as Amber List (Moderate Evidence).
Optic neuropathy v2.10 MECR Ivone Leong Tag for-review tag was added to gene: MECR.
Optic neuropathy v2.10 MECR Ivone Leong Phenotypes for gene: MECR were changed from Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities to Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities, 617282
Optic neuropathy v2.9 NBAS Ivone Leong Classified gene: NBAS as Amber List (moderate evidence)
Optic neuropathy v2.9 NBAS Ivone Leong Gene: nbas has been classified as Amber List (Moderate Evidence).
Optic neuropathy v2.8 NBAS Ivone Leong Classified gene: NBAS as No list
Optic neuropathy v2.8 NBAS Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark. NBAS is associated with an appropriate phenotype in OMIM and probably associated with an appropriate phenotype in Gene2Phenotype.

PMID: 31015584 describes another unrelated case where patients has variant in NBAS and also had optic atrophy.

PMID: 31761904 is a study that looked at defining the spectrum of phenotypes related to NBAS. There are > 3 cases of individuals with variants in NBAS who have optic atropy.

Therefore, there is enough evidence for this gene to be Green. This gene will be made Green at the next major review.
Optic neuropathy v2.8 NBAS Ivone Leong Gene: nbas has been removed from the panel.
Optic neuropathy v2.7 NBAS Ivone Leong Tag for-review tag was added to gene: NBAS.
Optic neuropathy v2.7 NBAS Ivone Leong Publications for gene: NBAS were set to 20577004; 26286438
Optic neuropathy v2.6 NBAS Ivone Leong Phenotypes for gene: NBAS were changed from Short stature, optic nerve atrophy, and Pelger-Huet anomaly to Short stature, optic nerve atrophy, and Pelger-Huet anomaly, 614800
Optic neuropathy v2.5 UCHL1 Ivone Leong Classified gene: UCHL1 as Amber List (moderate evidence)
Optic neuropathy v2.5 UCHL1 Ivone Leong Added comment: Comment on list classification: New gene added by Zornitza Stark. Based on provided evidence there is enough evidence to support a gene-disease association and Green status. However, this gene is currently rated Amber and tagged with "for-review" until the next major review at which point this gene should be made Green.
Optic neuropathy v2.5 UCHL1 Ivone Leong Gene: uchl1 has been classified as Amber List (Moderate Evidence).
Optic neuropathy v2.4 UCHL1 Ivone Leong Tag for-review tag was added to gene: UCHL1.
Optic neuropathy v2.4 UCHL1 Ivone Leong Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive (MIM#615491) to Spastic paraplegia 79, autosomal recessive, 615491
Optic neuropathy v2.3 OPA8 Eleanor Williams Tag ensembl_ids_known_missing tag was added to gene: OPA8.
Optic neuropathy v2.3 OPA6 Eleanor Williams Tag ensembl_ids_known_missing tag was added to gene: OPA6.
Optic neuropathy v2.3 OPA5 Eleanor Williams Tag ensembl_ids_known_missing tag was added to gene: OPA5.
Optic neuropathy v2.3 OPA4 Eleanor Williams Tag ensembl_ids_known_missing tag was added to gene: OPA4.
Optic neuropathy v2.3 OPA2 Eleanor Williams Tag ensembl_ids_known_missing tag was added to gene: OPA2.
Optic neuropathy v2.3 FDXR Sara Martins reviewed gene: FDXR: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 30250212, PMID: 28965846, PMID: 29040572; Phenotypes: Auditory neuropathy and optic atrophy (MIM 617717); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v2.3 MECR Sara Martins reviewed gene: MECR: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 27817865, PMID: 31137067; Phenotypes: Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v2.3 AFG3L2 Sara Martins reviewed gene: AFG3L2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 32219868; Phenotypes: Spastic ataxia 5, autosomal recessive (MIM#614487), Spinocerebellar ataxia 28 (MIM#610246); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic neuropathy v2.3 MCAT Zornitza Stark gene: MCAT was added
gene: MCAT was added to Optic neuropathy. Sources: Literature
Mode of inheritance for gene: MCAT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCAT were set to 31915829
Phenotypes for gene: MCAT were set to progressive autosomal recessive optic neuropathy
Review for gene: MCAT was set to RED
Added comment: Single family reported.
Sources: Literature
Optic neuropathy v2.3 UCHL1 Zornitza Stark gene: UCHL1 was added
gene: UCHL1 was added to Optic neuropathy. Sources: Expert list
Mode of inheritance for gene: UCHL1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UCHL1 were set to 29735986; 23359680; 28007905
Phenotypes for gene: UCHL1 were set to Spastic paraplegia 79, autosomal recessive (MIM#615491)
Review for gene: UCHL1 was set to GREEN
Added comment: Three families reported, optic atrophy is a consistent feature and onset of OA preceded onset of other neurological features in at least some of the reported individuals.
Sources: Expert list
Optic neuropathy v2.3 NBAS Zornitza Stark gene: NBAS was added
gene: NBAS was added to Optic neuropathy. Sources: Expert list
Mode of inheritance for gene: NBAS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NBAS were set to 20577004; 26286438
Phenotypes for gene: NBAS were set to Short stature, optic nerve atrophy, and Pelger-Huet anomaly
Review for gene: NBAS was set to GREEN
Added comment: This gene causes two recessive phenotypes: OA is not a feature of the infantile liver failure syndrome. It is however a consistent feature of the second condition: Short stature, optic nerve atrophy, and Pelger-Huet anomaly, MIM# 614800, which has predominantly been described in the Yakult.

PMID: 20577004 - Study of 30 Yakut families found ALL had OA, 33/34 patients had the same homozygous missense, founder very likely

PMID: 26286438 - 1 patient chet for a PTC and missense and had OA. Second patient (also chet PTC/missense) had NO OA.

Remains to be seen whether OA is an association with specific variants in this gene, and what the underlying mechanism for this is.
Sources: Expert list
Optic neuropathy v2.3 MECR Zornitza Stark gene: MECR was added
gene: MECR was added to Optic neuropathy. Sources: Expert list
Mode of inheritance for gene: MECR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MECR were set to 27817865; 31137067
Phenotypes for gene: MECR were set to Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities
Review for gene: MECR was set to GREEN
gene: MECR was marked as current diagnostic
Added comment: At least 6 families reported, optic atrophy is a consistent feature.
Sources: Expert list
Optic neuropathy v2.3 FDXR Zornitza Stark gene: FDXR was added
gene: FDXR was added to Optic neuropathy. Sources: Expert list
Mode of inheritance for gene: FDXR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FDXR were set to 30250212; 28965846
Phenotypes for gene: FDXR were set to Auditory neuropathy and optic atrophy, MIM#617717
Review for gene: FDXR was set to GREEN
Added comment: Six unrelated families reported with bi-allelic variants in this gene, optic atrophy is a consistent feature.
Sources: Expert list
Optic neuropathy v2.3 ATAD3A Zornitza Stark reviewed gene: ATAD3A: Rating: GREEN; Mode of pathogenicity: None; Publications: 27640307, 28652416; Phenotypes: Harel-Yoon syndrome, MIM#617183; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Optic neuropathy v2.3 AP3B2 Zornitza Stark gene: AP3B2 was added
gene: AP3B2 was added to Optic neuropathy. Sources: Expert list
Mode of inheritance for gene: AP3B2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AP3B2 were set to 27889060
Phenotypes for gene: AP3B2 were set to Early-onset epileptic encephalopathy with optic atrophy, MIM#617276
Review for gene: AP3B2 was set to GREEN
Added comment: Optic atrophy is a feature of this neurological disorder.
Sources: Expert list
Optic neuropathy v2.3 AFG3L2 Zornitza Stark reviewed gene: AFG3L2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29181157, 26539208, 30252181, 30389403; Phenotypes: Spastic ataxia 5, autosomal recessive (MIM#614487), Spinocerebellar ataxia 28 (MIM#610246); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Optic neuropathy v2.3 Sarah Leigh Panel version has been signed off
Optic neuropathy v2.0 Ivone Leong promoted panel to version 2.0
Optic neuropathy v1.121 Ivone Leong Panel types changed to Rare Disease 100K; GMS Rare Disease; GMS signed-off
Optic neuropathy v1.120 TMEM126A Sarah Leigh reviewed gene: TMEM126A: Rating: ; Mode of pathogenicity: None; Publications: 31119195; Phenotypes: ; Mode of inheritance: None
Optic neuropathy v1.120 TMEM126A Sarah Leigh Publications for gene: TMEM126A were set to 19327736; 20405026; 22815638; 30961538
Optic neuropathy v1.118 Ivone Leong List of related panels changed from Inherited optic neuropathies; R41 to Inherited optic neuropathies; R41; R42.2
Optic neuropathy v1.117 Ivone Leong List of related panels changed from Inherited optic neuropathies to Inherited optic neuropathies; R41
Optic neuropathy v1.116 SSBP1 Ivone Leong Publications for gene: SSBP1 were set to PMID: 31298765
Optic neuropathy v1.115 SSBP1 Anna de Burca Classified gene: SSBP1 as Green List (high evidence)
Optic neuropathy v1.115 SSBP1 Anna de Burca Gene: ssbp1 has been classified as Green List (High Evidence).
Optic neuropathy v1.114 SSBP1 Anna de Burca reviewed gene: SSBP1: Rating: GREEN; Mode of pathogenicity: Other; Publications: 31298765; Phenotypes: Autosomal dominant optic atrophy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Optic neuropathy v1.114 SSBP1 Tom Cullup changed review comment from: Sources: Expert list; to: Sources: Expert list

Variants identified to date are missense and putative mode of action is dominant-negative, therefore there is potential for exception to loss-of-function rule, but insufficient data to clearly demonstrate at the moment. There are lower than expected LoF variants in gnomAD, so cannot rule out pathogenic LoF variants.
Optic neuropathy v1.114 SSBP1 Tom Cullup gene: SSBP1 was added
gene: SSBP1 was added to Optic neuropathy. Sources: Expert list
Mode of inheritance for gene: SSBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SSBP1 were set to PMID: 31298765
Phenotypes for gene: SSBP1 were set to Autosomal dominant optic atrophy with variable retinal degeneration
Penetrance for gene: SSBP1 were set to Complete
Review for gene: SSBP1 was set to GREEN
Added comment: Sources: Expert list
Optic neuropathy v1.113 TMEM126A Ivone Leong Classified gene: TMEM126A as Green List (high evidence)
Optic neuropathy v1.113 TMEM126A Ivone Leong Added comment: Comment on list classification: Promoted from amber to green based on the additional on case that was found (PMID: 30961538).
Optic neuropathy v1.113 TMEM126A Ivone Leong Gene: tmem126a has been classified as Green List (High Evidence).
Optic neuropathy v1.112 TMEM126A Ivone Leong Publications for gene: TMEM126A were set to 19327736; 20405026; 22815638
Optic neuropathy v1.111 TMEM126A Ivone Leong edited their review of gene: TMEM126A: Added comment: PMID: 30961538 describes a study of 3 affected individuals from 2 unrelated families. A Turkish patient with optic atrophy has a homozygous splice donor variant (c.86+2 T<C) in TMEM126A. Two Iraqi siblings with optic atrophy were found to have a homozygous missense variant (p.S36L) in TMEM126A.; Changed publications: 30961538
Optic neuropathy v1.111 TIMM8A Ivone Leong Classified gene: TIMM8A as Amber List (moderate evidence)
Optic neuropathy v1.111 TIMM8A Ivone Leong Added comment: Comment on list classification: Promoted from red to amber. TIMM8A is associated with a phenotype in both OMIM and Gene2Phenotype. Optic atrophy appears to be a minor feature of the condition and based on previous reviews, it was decided that not enough evidence is available to promote this to a green. However, if any new variants that explains the phenotype is available in the future then promotion to green gene status can be considered.
Optic neuropathy v1.111 TIMM8A Ivone Leong Gene: timm8a has been classified as Amber List (Moderate Evidence).
Optic neuropathy v1.110 TMEM126A Ivone Leong Classified gene: TMEM126A as Amber List (moderate evidence)
Optic neuropathy v1.110 TMEM126A Ivone Leong Added comment: Comment on list classification: Promoted from red to amber. TMEM126A is associated with a phenotype in OMIM but not Gene2Phenotype. There are 2 publications (PMID: 19327736, 20405026, 22815638) reporting on unrelated patients with optic atrophy who have the same variant (c.163C>T, p.R55X) who are from Algeria, Morocco and Tunisia. Haplotype analysis was consistent with a founder affect (PMID: 19327736). Based on this, it was decided that there is not enough evidence to promote it to green.
Optic neuropathy v1.110 TMEM126A Ivone Leong Gene: tmem126a has been classified as Amber List (Moderate Evidence).
Optic neuropathy v1.109 TIMM8A Ivone Leong Publications for gene: TIMM8A were set to 20301395
Optic neuropathy v1.108 SPG7 Ivone Leong Classified gene: SPG7 as Green List (high evidence)
Optic neuropathy v1.108 SPG7 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. There are >3 unrelated cases with different variants reported. It is associated with a phenotype in OMIM but not in Gene2Phenotype. Based on this evidence and the expert review, the gene has been given a green rating.
Optic neuropathy v1.108 SPG7 Ivone Leong Gene: spg7 has been classified as Green List (High Evidence).
Optic neuropathy v1.107 SPG7 Ivone Leong Publications for gene: SPG7 were set to
Optic neuropathy v1.106 TMEM126A Ivone Leong Tag founder-effect tag was added to gene: TMEM126A.
Optic neuropathy v1.106 TMEM126A Ivone Leong Phenotypes for gene: TMEM126A were changed from Optic Atrophy, Recessive to Optic Atrophy, Recessive; Optic atrophy 7, 612989
Optic neuropathy v1.105 MFF Ivone Leong Classified gene: MFF as Green List (high evidence)
Optic neuropathy v1.105 MFF Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. The gene is associated with a phenotype in OMIM but not in Gene2Phenotype. There are 3 unrelated cases with different variants in this gene associated with optic atrophy and also based on the expert review, it was decided that there is enough evidence to promote this gene to a green rating.
Optic neuropathy v1.105 MFF Ivone Leong Gene: mff has been classified as Green List (High Evidence).
Optic neuropathy v1.104 MFF Ivone Leong Publications for gene: MFF were set to 30581454; 26783368
Optic neuropathy v1.103 DNM1L Ivone Leong Classified gene: DNM1L as Green List (high evidence)
Optic neuropathy v1.103 DNM1L Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. There are 3 unrelated cases with different variants in OMIM. It is associated with a phenotype in OMIM but not in Gene2Phenotype. Based on this evidence and the expert review, the gene has been given a green rating.
Optic neuropathy v1.103 DNM1L Ivone Leong Gene: dnm1l has been classified as Green List (High Evidence).
Optic neuropathy v1.102 DNM1L Ivone Leong Publications for gene: DNM1L were set to 28969390
Optic neuropathy v1.101 CISD2 Ivone Leong Classified gene: CISD2 as Green List (high evidence)
Optic neuropathy v1.101 CISD2 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. A phenotype is associated with CISD2 in OMIM and Gene2phenotype. Optic atrophy is a phenotype of Wolfram syndrome and there are >3 unrelated cases of different variants in this gene. Based on this evidence and the expert review it was decided that there is enough evidence to promote this gene to green.
Optic neuropathy v1.101 CISD2 Ivone Leong Gene: cisd2 has been classified as Green List (High Evidence).
Optic neuropathy v1.100 CISD2 Ivone Leong Publications for gene: CISD2 were set to
Optic neuropathy v1.99 C19orf12 Ivone Leong Classified gene: C19orf12 as Green List (high evidence)
Optic neuropathy v1.99 C19orf12 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. C19orf12 is associated with a phenotype in OMIM but not in Gene2Phenotype. There are >3 unrelated cases of different variants in OMIM. Based on this and the expert review, it was decided that there is enough evidence to promote this gene to a green rating.
Optic neuropathy v1.99 C19orf12 Ivone Leong Gene: c19orf12 has been classified as Green List (High Evidence).
Optic neuropathy v1.98 C12orf65 Ivone Leong Classified gene: C12orf65 as Green List (high evidence)
Optic neuropathy v1.98 C12orf65 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. C12orf65 is associated with a phenotype in OMIM and Gene2Phenotype. There are >3 unrelated cases with different variants in this gene described in OMIM associated with optic atrophy. Therefore, based on the former and the evidence provided by the expert review, there is enough evidence to promote this gene to green status.
Optic neuropathy v1.98 C12orf65 Ivone Leong Gene: c12orf65 has been classified as Green List (High Evidence).
Optic neuropathy v1.97 C12orf65 Ivone Leong Publications for gene: C12orf65 were set to 28091420; 25995486
Optic neuropathy v1.95 ZNHIT3 Ivone Leong Phenotypes for gene: ZNHIT3 were changed from to Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO) 260565
Optic neuropathy v1.94 ZNHIT3 Ivone Leong Publications for gene: ZNHIT3 were set to
Optic neuropathy v1.93 ZNHIT3 Ivone Leong Mode of inheritance for gene: ZNHIT3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.92 YME1L1 Ivone Leong Phenotypes for gene: YME1L1 were changed from to Optic atrophy 617302; sensorineural hearing impairment; ataxia; other CNS symptoms (OPA11)
Optic neuropathy v1.91 YME1L1 Ivone Leong Publications for gene: YME1L1 were set to
Optic neuropathy v1.90 YME1L1 Ivone Leong Mode of inheritance for gene: YME1L1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.89 TSFM Ivone Leong Phenotypes for gene: TSFM were changed from to COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 3, 610505
Optic neuropathy v1.88 TSFM Ivone Leong Publications for gene: TSFM were set to
Optic neuropathy v1.87 TSFM Ivone Leong Mode of inheritance for gene: TSFM was changed from to BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.86 TBC1D20 Ivone Leong Phenotypes for gene: TBC1D20 were changed from to WARBURG MICRO SYNDROME 4 615663
Optic neuropathy v1.85 TBC1D20 Ivone Leong Mode of inheritance for gene: TBC1D20 was changed from to BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.84 SPG7 Ivone Leong Phenotypes for gene: SPG7 were changed from to SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE, 607259
Optic neuropathy v1.83 SPG7 Ivone Leong Mode of inheritance for gene: SPG7 was changed from to BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.82 SDHA Ivone Leong Phenotypes for gene: SDHA were changed from to Leigh syndrome, 256000; mitochondrial respiratory chain complex II deficiency 252011
Optic neuropathy v1.81 SDHA Ivone Leong Publications for gene: SDHA were set to
Optic neuropathy v1.80 SDHA Ivone Leong Mode of inheritance for gene: SDHA was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic neuropathy v1.79 RAB3GAP1 Ivone Leong Phenotypes for gene: RAB3GAP1 were changed from to WARBURG MICRO SYNDROME 1, 600118
Optic neuropathy v1.78 RAB3GAP1 Ivone Leong Publications for gene: RAB3GAP1 were set to
Optic neuropathy v1.77 RAB3GAP1 Ivone Leong Mode of inheritance for gene: RAB3GAP1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.76 NEFH Ivone Leong Phenotypes for gene: NEFH were changed from to CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2CC, 616924
Optic neuropathy v1.75 NEFH Ivone Leong Mode of inheritance for gene: NEFH was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Optic neuropathy v1.74 NDUFS3 Ivone Leong Phenotypes for gene: NDUFS3 were changed from to Mitochondrial complex I deficiency, nuclear type 8, 618230
Optic neuropathy v1.73 NDUFS3 Ivone Leong Publications for gene: NDUFS3 were set to
Optic neuropathy v1.72 NDUFS3 Ivone Leong Mode of inheritance for gene: NDUFS3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.71 NDUFS2 Ivone Leong Phenotypes for gene: NDUFS2 were changed from to Mitochondrial complex I deficiency, nuclear type 6, 618228
Optic neuropathy v1.70 NDUFS2 Ivone Leong Publications for gene: NDUFS2 were set to
Optic neuropathy v1.69 NDUFS2 Ivone Leong Mode of inheritance for gene: NDUFS2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.68 NDUFS1 Ivone Leong Phenotypes for gene: NDUFS1 were changed from to MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 5, 618226
Optic neuropathy v1.67 NDUFS1 Ivone Leong Mode of inheritance for gene: NDUFS1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.66 MTPAP Ivone Leong Phenotypes for gene: MTPAP were changed from to SPASTIC ATAXIA 4, AUTOSOMAL RECESSIVE, 613672
Optic neuropathy v1.65 MTPAP Ivone Leong Mode of inheritance for gene: MTPAP was changed from to BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.64 LYST Ivone Leong Publications for gene: LYST were set to PMID: 26307451
Optic neuropathy v1.63 KIF7 Ivone Leong Phenotypes for gene: KIF7 were changed from to ACROCALLOSAL SYNDROME, 200990
Optic neuropathy v1.62 KIF7 Ivone Leong Mode of inheritance for gene: KIF7 was changed from to BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.61 GP1BA Ivone Leong Mode of inheritance for gene: GP1BA was changed from to BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.60 FXN Ivone Leong Phenotypes for gene: FXN were changed from to Friedreich ataxia (FRDA), 229300
Optic neuropathy v1.59 FXN Ivone Leong Publications for gene: FXN were set to
Optic neuropathy v1.58 FXN Ivone Leong Mode of inheritance for gene: FXN was changed from to BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.57 DNAJC19 Ivone Leong Phenotypes for gene: DNAJC19 were changed from to 3-METHYLGLUTACONIC ACIDURIA, TYPE V, 610198
Optic neuropathy v1.56 DNAJC19 Ivone Leong Publications for gene: DNAJC19 were set to
Optic neuropathy v1.55 DNAJC19 Ivone Leong Mode of inheritance for gene: DNAJC19 was changed from to BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.54 AUH Ivone Leong Phenotypes for gene: AUH were changed from to 3-METHYLGLUTACONIC ACIDURIA, TYPE I, 250950
Optic neuropathy v1.53 AUH Ivone Leong Mode of inheritance for gene: AUH was changed from to BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.52 ATAD3A Ivone Leong Phenotypes for gene: ATAD3A were changed from to Harel-Yoon syndrome: optic atrophy, peripheral neuropathy, delayed psychomotor development, intellectual disability, spastic paraplegia (HAYOS), 617183
Optic neuropathy v1.51 ATAD3A Ivone Leong Publications for gene: ATAD3A were set to
Optic neuropathy v1.50 ATAD3A Ivone Leong Mode of inheritance for gene: ATAD3A was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic neuropathy v1.49 ALG3 Ivone Leong Phenotypes for gene: ALG3 were changed from to CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Id, 601110
Optic neuropathy v1.48 ALG3 Ivone Leong Mode of inheritance for gene: ALG3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.47 POLG Ivone Leong Phenotypes for gene: POLG were changed from to PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL DOMINANT 1, 157640; PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE 1, 258450
Optic neuropathy v1.46 POLG Ivone Leong Mode of inheritance for gene: POLG was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic neuropathy v1.45 MFF Ivone Leong Phenotypes for gene: MFF were changed from to Encephalopathy due to defective mitochondrial and peroxisomal fission 2, 617086
Optic neuropathy v1.44 MFF Ivone Leong Publications for gene: MFF were set to
Optic neuropathy v1.43 MFF Ivone Leong Mode of inheritance for gene: MFF was changed from to BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.42 DNM1L Ivone Leong Phenotypes for gene: DNM1L were changed from to OPTIC ATROPHY 5, 610708
Optic neuropathy v1.41 DNM1L Ivone Leong Publications for gene: DNM1L were set to
Optic neuropathy v1.40 DNM1L Ivone Leong Mode of inheritance for gene: DNM1L was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Optic neuropathy v1.39 CISD2 Ivone Leong Phenotypes for gene: CISD2 were changed from to WOLFRAM SYNDROME 2, 604928
Optic neuropathy v1.38 CISD2 Ivone Leong Mode of inheritance for gene: CISD2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.37 C19orf12 Ivone Leong Phenotypes for gene: C19orf12 were changed from to SPASTIC PARAPLEGIA 43, AUTOSOMAL RECESSIVE, 615043; NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 4, 614298
Optic neuropathy v1.36 C19orf12 Ivone Leong Publications for gene: C19orf12 were set to
Optic neuropathy v1.35 C19orf12 Ivone Leong Mode of inheritance for gene: C19orf12 was changed from to BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.34 C12orf65 Ivone Leong Phenotypes for gene: C12orf65 were changed from to SPASTIC PARAPLEGIA 55, AUTOSOMAL RECESSIVE, 615035
Optic neuropathy v1.33 C12orf65 Ivone Leong Publications for gene: C12orf65 were set to
Optic neuropathy v1.32 C12orf65 Ivone Leong Mode of inheritance for gene: C12orf65 was changed from to BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.31 AFG3L2 Ivone Leong Phenotypes for gene: AFG3L2 were changed from to SPASTIC ATAXIA 5, AUTOSOMAL RECESSIVE, 614487; SPINOCEREBELLAR ATAXIA 28, 610246
Optic neuropathy v1.30 AFG3L2 Ivone Leong Publications for gene: AFG3L2 were set to
Optic neuropathy v1.29 AFG3L2 Ivone Leong Mode of inheritance for gene: AFG3L2 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic neuropathy v1.28 ZNHIT3 Tom Cullup reviewed gene: ZNHIT3: Rating: RED; Mode of pathogenicity: ; Publications: 28335020; Phenotypes: Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO) 260565; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.28 YME1L1 Tom Cullup reviewed gene: YME1L1: Rating: RED; Mode of pathogenicity: ; Publications: 30544562; Phenotypes: Optic atrophy 617302, sensorineural hearing impairment, ataxia, other CNS symptoms (OPA11); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.28 TSFM Tom Cullup reviewed gene: TSFM: Rating: RED; Mode of pathogenicity: ; Publications: 25037205; Phenotypes: COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 3, 610505; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.28 TBC1D20 Tom Cullup reviewed gene: TBC1D20: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: WARBURG MICRO SYNDROME 4 615663; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Optic neuropathy v1.28 SDHA Tom Cullup reviewed gene: SDHA: Rating: RED; Mode of pathogenicity: ; Publications: 27683074; Phenotypes: Leigh syndrome, 256000, mitochondrial respiratory chain complex II deficiency 252011; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic neuropathy v1.28 RAB3GAP1 Tom Cullup reviewed gene: RAB3GAP1: Rating: RED; Mode of pathogenicity: ; Publications: 26421802; Phenotypes: WARBURG MICRO SYNDROME 1, 600118; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Optic neuropathy v1.28 NEFH Tom Cullup reviewed gene: NEFH: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2CC, 616924; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Optic neuropathy v1.28 NDUFS3 Tom Cullup reviewed gene: NDUFS3: Rating: RED; Mode of pathogenicity: ; Publications: 14729820; Phenotypes: Mitochondrial complex I deficiency, nuclear type 8, 618230; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.28 NDUFS2 Tom Cullup reviewed gene: NDUFS2: Rating: RED; Mode of pathogenicity: ; Publications: 28031252; Phenotypes: Mitochondrial complex I deficiency, nuclear type 6, 618228; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.28 NDUFS1 Tom Cullup reviewed gene: NDUFS1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 5, 618226; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.28 MTPAP Tom Cullup reviewed gene: MTPAP: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: SPASTIC ATAXIA 4, AUTOSOMAL RECESSIVE, 613672; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.28 LYST Tom Cullup reviewed gene: LYST: Rating: RED; Mode of pathogenicity: ; Publications: 26307451, 23521865; Phenotypes: Optic neuropathy in late-onset neurodegenerative Ch diak Higashi syndrome lacking features of ocular albinism; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.28 KIF7 Tom Cullup reviewed gene: KIF7: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ACROCALLOSAL SYNDROME, 200990; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Optic neuropathy v1.28 GP1BA Tom Cullup reviewed gene: GP1BA: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: {Nonarteritic anterior ischemic optic neuropathy, susceptibility to}; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.28 FXN Tom Cullup reviewed gene: FXN: Rating: RED; Mode of pathogenicity: ; Publications: 19268652; Phenotypes: Friedreich ataxia (FRDA), 229300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.28 DNAJC19 Tom Cullup reviewed gene: DNAJC19: Rating: RED; Mode of pathogenicity: ; Publications: 27054461, 16055927; Phenotypes: 3-METHYLGLUTACONIC ACIDURIA, TYPE V, 610198; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.28 AUH Tom Cullup reviewed gene: AUH: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: 3-METHYLGLUTACONIC ACIDURIA, TYPE I, 250950; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.28 ATAD3A Tom Cullup reviewed gene: ATAD3A: Rating: RED; Mode of pathogenicity: ; Publications: 27640307; Phenotypes: Harel-Yoon syndrome: optic atrophy, peripheral neuropathy, delayed psychomotor development, intellectual disability, spastic paraplegia (HAYOS), 617183; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic neuropathy v1.28 ALG3 Tom Cullup reviewed gene: ALG3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Id, 601110; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Optic neuropathy v1.28 WFS1 Tom Cullup reviewed gene: WFS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Wolfram syndrome; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Optic neuropathy v1.28 TMEM126A Tom Cullup reviewed gene: TMEM126A: Rating: GREEN; Mode of pathogenicity: ; Publications: 19327736, 20405026, 22815638; Phenotypes: Optic Atrophy, Recessive; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Optic neuropathy v1.28 TIMM8A Tom Cullup reviewed gene: TIMM8A: Rating: GREEN; Mode of pathogenicity: ; Publications: 11803487; Phenotypes: deafness-dystonia-optic neuropathy syndrome, Mohr-Tranebjaerg syndrome; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Optic neuropathy v1.28 SPG7 Tom Cullup reviewed gene: SPG7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE, 607259; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Optic neuropathy v1.28 SLC52A2 Tom Cullup reviewed gene: SLC52A2: Rating: GREEN; Mode of pathogenicity: ; Publications: 23243084, 22864630; Phenotypes: Brown-Vialetto-Van Laere syndrome 2, 614707; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.28 SLC25A46 Tom Cullup reviewed gene: SLC25A46: Rating: GREEN; Mode of pathogenicity: ; Publications: 26168012, 28369803; Phenotypes: Neuropathy, hereditary motor and sensory, type VIB, 616505; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.28 RTN4IP1 Tom Cullup reviewed gene: RTN4IP1: Rating: GREEN; Mode of pathogenicity: ; Publications: 26593267; Phenotypes: early-onset recessive optic neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.28 POLG Tom Cullup reviewed gene: POLG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL DOMINANT 1, 157640, PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE 1, 258450; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic neuropathy v1.28 OPA3 Tom Cullup reviewed gene: OPA3: Rating: GREEN; Mode of pathogenicity: ; Publications: 25159689, 26190011; Phenotypes: Autosomal Dominant Optic Atrophy, optic atrophy and cataracts, Optic atrophy 3 with cataract; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Optic neuropathy v1.28 OPA1 Tom Cullup reviewed gene: OPA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Optic atrophy 1 165500, Optic atrophy plus syndrome 125250; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Optic neuropathy v1.28 NR2F1 Tom Cullup reviewed gene: NR2F1: Rating: GREEN; Mode of pathogenicity: ; Publications: 29410510, 28963436, 28654857, 26986877, 24462372, 23300014; Phenotypes: Bosch-Boonstra-Schaaf optic atrophy syndrome, 615722; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Optic neuropathy v1.28 MT-ND6 Tom Cullup reviewed gene: MT-ND6: Rating: GREEN; Mode of pathogenicity: ; Publications: 26448634, 24884847, 24417559, 24398099; Phenotypes: Leber hereditary optic neuropathy, Nystagmus, severe infantile-onset complex I deficiency; Mode of inheritance: MITOCHONDRIAL
Optic neuropathy v1.28 MT-ND4 Tom Cullup reviewed gene: MT-ND4: Rating: GREEN; Mode of pathogenicity: ; Publications: 26448634, 20301353, 27159682, 26683077, 23805034, 23665487, 22553750; Phenotypes: Leber's hereditary optic neuropathy; Mode of inheritance: MITOCHONDRIAL
Optic neuropathy v1.28 MT-ND1 Tom Cullup reviewed gene: MT-ND1: Rating: GREEN; Mode of pathogenicity: ; Publications: 26448634, 27449621, 20301353, 27177320, 24884847, 24800637, 23665487; Phenotypes: Optic neuropathy and nystagmus, External ophthalmoplegia, Leber's hereditary optic neuropathy; Mode of inheritance: MITOCHONDRIAL
Optic neuropathy v1.28 MT-ATP6 Tom Cullup reviewed gene: MT-ATP6: Rating: GREEN; Mode of pathogenicity: ; Publications: 7726182, 10676807, 26448634, 26252090, 24118886 (functional evidence), 23266623; Phenotypes: Leber optic atrophy, 535000, neurogenic weakness, ataxia, and retinitis pigmentosa, retinopathy; Mode of inheritance: MITOCHONDRIAL
Optic neuropathy v1.28 MFN2 Tom Cullup reviewed gene: MFN2: Rating: GREEN; Mode of pathogenicity: ; Publications: 26955893, 26306937, 21715711; Phenotypes: Optic Atrophy, Hereditary motor and sensory neuropathy VIA, Charcot-Marie-Tooth disease, axonal, type 2A2A (AD), 609260, Charcot-Marie-Tooth disease, axonal, type 2A2B (AR), 617087, Hereditary motor and sensory neuropathy VIA (AD), 601152; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Optic neuropathy v1.28 MFF Tom Cullup reviewed gene: MFF: Rating: GREEN; Mode of pathogenicity: ; Publications: 30581454, 26783368; Phenotypes: Encephalopathy due to defective mitochondrial and peroxisomal fission 2, 617086; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.28 DNM1L Tom Cullup reviewed gene: DNM1L: Rating: GREEN; Mode of pathogenicity: ; Publications: 28969390; Phenotypes: OPTIC ATROPHY 5, 610708; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Optic neuropathy v1.28 CISD2 Tom Cullup reviewed gene: CISD2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: WOLFRAM SYNDROME 2, 604928; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.28 C19orf12 Tom Cullup reviewed gene: C19orf12: Rating: GREEN; Mode of pathogenicity: ; Publications: 27772766, 26187298, 24209434, 22584950; Phenotypes: SPASTIC PARAPLEGIA 43, AUTOSOMAL RECESSIVE, 615043, NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 4, 614298; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.28 C12orf65 Tom Cullup reviewed gene: C12orf65: Rating: GREEN; Mode of pathogenicity: ; Publications: 28091420, 25995486; Phenotypes: SPASTIC PARAPLEGIA 55, AUTOSOMAL RECESSIVE, 615035; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Optic neuropathy v1.28 ACO2 Tom Cullup reviewed gene: ACO2: Rating: GREEN; Mode of pathogenicity: ; Publications: 25351951, 22405087; Phenotypes: Optic atrophy 9, 616289, optic atrophy, nystagmus, Infantile cerebellar-retinal degeneration; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v1.28 AFG3L2 Tom Cullup reviewed gene: AFG3L2: Rating: AMBER; Mode of pathogenicity: ; Publications: 29181157, 26539208, 30544562; Phenotypes: SPASTIC ATAXIA 5, AUTOSOMAL RECESSIVE, 614487, SPINOCEREBELLAR ATAXIA 28, 610246; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic neuropathy v1.27 ZNHIT3 Ivone Leong gene: ZNHIT3 was added
gene: ZNHIT3 was added to Optic neuropathy. Sources: London North GLH,Expert Review Red
Mode of inheritance for gene: ZNHIT3 was set to
Optic neuropathy v1.27 YME1L1 Ivone Leong gene: YME1L1 was added
gene: YME1L1 was added to Optic neuropathy. Sources: London North GLH,Expert Review Red
Mode of inheritance for gene: YME1L1 was set to
Optic neuropathy v1.27 TSFM Ivone Leong gene: TSFM was added
gene: TSFM was added to Optic neuropathy. Sources: London North GLH,Expert Review Red
Mode of inheritance for gene: TSFM was set to
Optic neuropathy v1.27 TBC1D20 Ivone Leong gene: TBC1D20 was added
gene: TBC1D20 was added to Optic neuropathy. Sources: London North GLH,Expert Review Red
Mode of inheritance for gene: TBC1D20 was set to
Optic neuropathy v1.27 SDHA Ivone Leong gene: SDHA was added
gene: SDHA was added to Optic neuropathy. Sources: London North GLH,Expert Review Red
Mode of inheritance for gene: SDHA was set to
Optic neuropathy v1.27 RAB3GAP1 Ivone Leong gene: RAB3GAP1 was added
gene: RAB3GAP1 was added to Optic neuropathy. Sources: London North GLH,Expert Review Red
Mode of inheritance for gene: RAB3GAP1 was set to
Optic neuropathy v1.27 NEFH Ivone Leong gene: NEFH was added
gene: NEFH was added to Optic neuropathy. Sources: London North GLH,Expert Review Red
Mode of inheritance for gene: NEFH was set to
Optic neuropathy v1.27 NDUFS3 Ivone Leong gene: NDUFS3 was added
gene: NDUFS3 was added to Optic neuropathy. Sources: London North GLH,Expert Review Red
Mode of inheritance for gene: NDUFS3 was set to
Optic neuropathy v1.27 NDUFS2 Ivone Leong gene: NDUFS2 was added
gene: NDUFS2 was added to Optic neuropathy. Sources: London North GLH,Expert Review Red
Mode of inheritance for gene: NDUFS2 was set to
Optic neuropathy v1.27 NDUFS1 Ivone Leong gene: NDUFS1 was added
gene: NDUFS1 was added to Optic neuropathy. Sources: London North GLH,Expert Review Red
Mode of inheritance for gene: NDUFS1 was set to
Optic neuropathy v1.27 MTPAP Ivone Leong gene: MTPAP was added
gene: MTPAP was added to Optic neuropathy. Sources: London North GLH,Expert Review Red
Mode of inheritance for gene: MTPAP was set to
Optic neuropathy v1.27 LYST Ivone Leong Source London North GLH was added to LYST.
Optic neuropathy v1.27 KIF7 Ivone Leong gene: KIF7 was added
gene: KIF7 was added to Optic neuropathy. Sources: London North GLH,Expert Review Red
Mode of inheritance for gene: KIF7 was set to
Optic neuropathy v1.27 GP1BA Ivone Leong Source London North GLH was added to GP1BA.
Optic neuropathy v1.27 FXN Ivone Leong gene: FXN was added
gene: FXN was added to Optic neuropathy. Sources: London North GLH,Expert Review Red
Mode of inheritance for gene: FXN was set to
Optic neuropathy v1.27 DNAJC19 Ivone Leong gene: DNAJC19 was added
gene: DNAJC19 was added to Optic neuropathy. Sources: London North GLH,Expert Review Red
Mode of inheritance for gene: DNAJC19 was set to
Optic neuropathy v1.27 AUH Ivone Leong gene: AUH was added
gene: AUH was added to Optic neuropathy. Sources: London North GLH,Expert Review Red
Mode of inheritance for gene: AUH was set to
Optic neuropathy v1.27 ATAD3A Ivone Leong gene: ATAD3A was added
gene: ATAD3A was added to Optic neuropathy. Sources: London North GLH,Expert Review Red
Mode of inheritance for gene: ATAD3A was set to
Optic neuropathy v1.27 ALG3 Ivone Leong gene: ALG3 was added
gene: ALG3 was added to Optic neuropathy. Sources: London North GLH,Expert Review Red
Mode of inheritance for gene: ALG3 was set to
Optic neuropathy v1.27 WFS1 Ivone Leong Source London North GLH was added to WFS1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Optic neuropathy v1.27 TMEM126A Ivone Leong Source London North GLH was added to TMEM126A.
Optic neuropathy v1.27 TIMM8A Ivone Leong Source London North GLH was added to TIMM8A.
Optic neuropathy v1.27 SPG7 Ivone Leong Source London North GLH was added to SPG7.
Optic neuropathy v1.27 SLC52A2 Ivone Leong Source London North GLH was added to SLC52A2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Optic neuropathy v1.27 SLC25A46 Ivone Leong Source London North GLH was added to SLC25A46.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Optic neuropathy v1.27 RTN4IP1 Ivone Leong Source London North GLH was added to RTN4IP1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Optic neuropathy v1.27 POLG Ivone Leong gene: POLG was added
gene: POLG was added to Optic neuropathy. Sources: London North GLH,Expert Review Amber
Mode of inheritance for gene: POLG was set to
Optic neuropathy v1.27 OPA3 Ivone Leong Source London North GLH was added to OPA3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Optic neuropathy v1.27 OPA1 Ivone Leong Source London North GLH was added to OPA1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Optic neuropathy v1.27 NR2F1 Ivone Leong Source London North GLH was added to NR2F1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Optic neuropathy v1.27 MT-ND6 Ivone Leong Source London North GLH was added to MT-ND6.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Optic neuropathy v1.27 MT-ND4 Ivone Leong Source London North GLH was added to MT-ND4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Optic neuropathy v1.27 MT-ND1 Ivone Leong Source London North GLH was added to MT-ND1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Optic neuropathy v1.27 MT-ATP6 Ivone Leong Source London North GLH was added to MT-ATP6.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Optic neuropathy v1.27 MFN2 Ivone Leong Source London North GLH was added to MFN2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Optic neuropathy v1.27 MFF Ivone Leong gene: MFF was added
gene: MFF was added to Optic neuropathy. Sources: London North GLH,Expert Review Amber
Mode of inheritance for gene: MFF was set to
Optic neuropathy v1.27 DNM1L Ivone Leong gene: DNM1L was added
gene: DNM1L was added to Optic neuropathy. Sources: London North GLH,Expert Review Amber
Mode of inheritance for gene: DNM1L was set to
Optic neuropathy v1.27 CISD2 Ivone Leong gene: CISD2 was added
gene: CISD2 was added to Optic neuropathy. Sources: London North GLH,Expert Review Amber
Mode of inheritance for gene: CISD2 was set to
Optic neuropathy v1.27 C19orf12 Ivone Leong gene: C19orf12 was added
gene: C19orf12 was added to Optic neuropathy. Sources: London North GLH,Expert Review Amber
Mode of inheritance for gene: C19orf12 was set to
Optic neuropathy v1.27 C12orf65 Ivone Leong gene: C12orf65 was added
gene: C12orf65 was added to Optic neuropathy. Sources: London North GLH,Expert Review Amber
Mode of inheritance for gene: C12orf65 was set to
Optic neuropathy v1.27 ACO2 Ivone Leong Source London North GLH was added to ACO2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Optic neuropathy v1.27 AFG3L2 Ivone Leong gene: AFG3L2 was added
gene: AFG3L2 was added to Optic neuropathy. Sources: London North GLH,Expert Review Amber
Mode of inheritance for gene: AFG3L2 was set to
Optic neuropathy v1.26 WFS1 Louise Daugherty Phenotypes for gene: WFS1 were changed from Wolfram syndrome; Wolfram syndrome to Wolfram syndrome
Optic neuropathy v1.24 Ellen McDonagh Panel name changed from Inherited optic neuropathies to Optic neuropathy
List of related panels changed from to Inherited optic neuropathies
Optic neuropathy v1.23 Ellen McDonagh List of related panels changed from to
Panel types changed to Rare Disease 100K; GMS Rare Disease
Optic neuropathy SLC52A2 Ellen McDonagh classified SLC52A2 as Green List (high evidence)
Optic neuropathy SLC52A2 Ellen McDonagh commented on gene: SLC52A2
Optic neuropathy SLC52A2 Ellen McDonagh commented on gene: SLC52A2
Optic neuropathy SLC52A2 Ellen McDonagh Added gene to panel
Optic neuropathy MFN2 Panagiotis Sergouniotis reviewed gene: MFN2
Optic neuropathy OPA3 Panagiotis Sergouniotis reviewed gene: OPA3
Optic neuropathy MT-ND4 Ellen McDonagh edited their review of MT-ND4
Optic neuropathy SLC25A46 Sarah Leigh classified SLC25A46 as green
Optic neuropathy SLC25A46 Sarah Leigh edited their review of SLC25A46
Optic neuropathy SLC25A46 Sarah Leigh added SLC25A46 to panel
Optic neuropathy SLC25A46 Sarah Leigh reviewed SLC25A46
Optic neuropathy OPA2 Louise Daugherty classified OPA2 as grey
Optic neuropathy OPA2 Louise Daugherty commented on OPA2
Optic neuropathy OPA4 Louise Daugherty classified OPA4 as grey
Optic neuropathy OPA4 Louise Daugherty commented on OPA4
Optic neuropathy OPA8 Louise Daugherty classified OPA8 as grey
Optic neuropathy OPA8 Louise Daugherty commented on OPA8
Optic neuropathy OPA6 Louise Daugherty classified OPA6 as grey
Optic neuropathy OPA6 Louise Daugherty commented on OPA6
Optic neuropathy OPA5 Louise Daugherty classified OPA5 as grey
Optic neuropathy OPA5 Louise Daugherty commented on OPA5
Optic neuropathy OPA8 Ellen McDonagh commented on OPA8
Optic neuropathy OPA6 Ellen McDonagh commented on OPA6
Optic neuropathy OPA5 Ellen McDonagh commented on OPA5
Optic neuropathy OPA4 Ellen McDonagh commented on OPA4
Optic neuropathy OPA2 Ellen McDonagh commented on OPA2
Optic neuropathy Ellen McDonagh promoted panel to version 1
Optic neuropathy Ellen McDonagh approved panel
Optic neuropathy WFS1 Ellen Thomas marked WFS1 as ready
Optic neuropathy WFS1 Ellen Thomas classified WFS1 as green
Optic neuropathy WFS1 Ellen Thomas commented on WFS1
Optic neuropathy TIMM8A Ellen Thomas marked TIMM8A as ready
Optic neuropathy TIMM8A Ellen Thomas classified TIMM8A as red
Optic neuropathy TIMM8A Ellen Thomas commented on TIMM8A
Optic neuropathy SPG7 Ellen Thomas marked SPG7 as ready
Optic neuropathy SPG7 Ellen Thomas classified SPG7 as red
Optic neuropathy SPG7 Ellen Thomas commented on SPG7
Optic neuropathy RTN4IP1 Ellen Thomas marked RTN4IP1 as ready
Optic neuropathy RTN4IP1 Ellen Thomas classified RTN4IP1 as green
Optic neuropathy RTN4IP1 Ellen Thomas commented on RTN4IP1
Optic neuropathy NR2F1 Ellen Thomas marked NR2F1 as ready
Optic neuropathy NR2F1 Ellen Thomas classified NR2F1 as green
Optic neuropathy NR2F1 Ellen Thomas commented on NR2F1
Optic neuropathy MT-ND6 Ellen Thomas marked MT-ND6 as ready
Optic neuropathy MT-ND6 Ellen Thomas commented on MT-ND6
Optic neuropathy MT-ND6 Ellen Thomas classified MT-ND6 as green
Optic neuropathy MT-ND4 Ellen Thomas marked MT-ND4 as ready
Optic neuropathy MT-ND4 Ellen Thomas classified MT-ND4 as green
Optic neuropathy MT-ND4 Ellen Thomas commented on MT-ND4
Optic neuropathy MFN2 Ellen Thomas marked MFN2 as ready
Optic neuropathy MFN2 Ellen Thomas classified MFN2 as green
Optic neuropathy MFN2 Ellen Thomas commented on MFN2
Optic neuropathy LYST Ellen McDonagh classified LYST as red
Optic neuropathy LYST Ellen McDonagh added LYST to panel
Optic neuropathy LYST Ellen McDonagh reviewed LYST
Optic neuropathy ACO2 Ellen McDonagh marked ACO2 as ready
Optic neuropathy TMEM126A Ellen McDonagh marked TMEM126A as ready
Optic neuropathy OPA8 Ellen McDonagh marked OPA8 as ready
Optic neuropathy OPA6 Ellen McDonagh marked OPA6 as ready
Optic neuropathy OPA5 Ellen McDonagh marked OPA5 as ready
Optic neuropathy OPA4 Ellen McDonagh marked OPA4 as ready
Optic neuropathy OPA2 Ellen McDonagh marked OPA2 as ready
Optic neuropathy OPA2 Ellen McDonagh commented on OPA2
Optic neuropathy OPA2 Ellen McDonagh added OPA2 to panel
Optic neuropathy OPA2 Ellen McDonagh reviewed OPA2
Optic neuropathy ACO2 Ellen McDonagh classified ACO2 as green
Optic neuropathy ACO2 Ellen McDonagh classified ACO2 as red
Optic neuropathy ACO2 Ellen McDonagh added ACO2 to panel
Optic neuropathy ACO2 Ellen McDonagh reviewed ACO2
Optic neuropathy OPA5 Ellen McDonagh added OPA5 to panel
Optic neuropathy OPA5 Ellen McDonagh reviewed OPA5
Optic neuropathy OPA4 Ellen McDonagh added OPA4 to panel
Optic neuropathy OPA4 Ellen McDonagh reviewed OPA4
Optic neuropathy OPA8 Ellen McDonagh classified OPA8 as red
Optic neuropathy OPA8 Ellen McDonagh added OPA8 to panel
Optic neuropathy OPA8 Ellen McDonagh reviewed OPA8
Optic neuropathy OPA6 Ellen McDonagh marked OPA6 as ready
Optic neuropathy OPA6 Ellen McDonagh classified OPA6 as red
Optic neuropathy OPA6 Ellen McDonagh added OPA6 to panel
Optic neuropathy OPA6 Ellen McDonagh reviewed OPA6
Optic neuropathy TMEM126A Ellen McDonagh classified TMEM126A as red
Optic neuropathy TIMM8A Ellen McDonagh classified TIMM8A as amber
Optic neuropathy TIMM8A Ellen McDonagh commented on TIMM8A
Optic neuropathy WFS1 Ellen McDonagh classified WFS1 as amber
Optic neuropathy WFS1 Ellen McDonagh commented on WFS1
Optic neuropathy TIMM8A Ellen McDonagh classified TIMM8A as amber
Optic neuropathy SPG7 Ellen McDonagh classified SPG7 as amber
Optic neuropathy SPG7 Ellen McDonagh commented on SPG7
Optic neuropathy NR2F1 Ellen McDonagh classified NR2F1 as amber
Optic neuropathy NR2F1 Ellen McDonagh classified NR2F1 as green
Optic neuropathy NR2F1 Ellen McDonagh commented on NR2F1
Optic neuropathy NR2F1 Ellen McDonagh classified NR2F1 as red
Optic neuropathy MT-ND6 Ellen McDonagh commented on MT-ND6
Optic neuropathy MT-ND6 Ellen McDonagh classified MT-ND6 as amber
Optic neuropathy MT-ND4 Ellen McDonagh classified MT-ND4 as amber
Optic neuropathy MT-ND4 Ellen McDonagh commented on MT-ND4
Optic neuropathy MT-ND1 Ellen McDonagh marked MT-ND1 as ready
Optic neuropathy MT-ND1 Ellen McDonagh classified MT-ND1 as green
Optic neuropathy MT-ND1 Ellen McDonagh commented on MT-ND1
Optic neuropathy MT-ATP6 Ellen McDonagh marked MT-ATP6 as ready
Optic neuropathy MT-ATP6 Ellen McDonagh classified MT-ATP6 as green
Optic neuropathy MT-ATP6 Ellen McDonagh commented on MT-ATP6
Optic neuropathy MFN2 Ellen McDonagh classified MFN2 as amber
Optic neuropathy MFN2 Ellen McDonagh commented on MFN2
Optic neuropathy GP1BA Ellen McDonagh marked GP1BA as ready
Optic neuropathy GP1BA Ellen McDonagh classified GP1BA as red
Optic neuropathy GP1BA Ellen McDonagh commented on GP1BA
Optic neuropathy TMEM126A Ellen McDonagh commented on TMEM126A
Optic neuropathy TMEM126A Ellen McDonagh classified TMEM126A as amber
Optic neuropathy RTN4IP1 Ellen McDonagh classified RTN4IP1 as amber
Optic neuropathy RTN4IP1 Ellen McDonagh added RTN4IP1 to panel
Optic neuropathy RTN4IP1 Ellen McDonagh reviewed RTN4IP1
Optic neuropathy OPA3 Ellen McDonagh marked OPA3 as ready
Optic neuropathy OPA3 Ellen McDonagh commented on OPA3
Optic neuropathy OPA1 Ellen McDonagh marked OPA1 as ready
Optic neuropathy OPA1 Ellen McDonagh commented on OPA1