Description
This panel is used for clinical indication 'R41 Optic neuropathy' and test type 'R42.2 Leber hereditary optic neuropathy' in the NHS Genomic Medicine Service.

Further information on the testing criteria and any overlapping clinical indications can be found within (https://www.england.nhs.uk/publication/national-genomic-test-directories/) under 'R41 Optic neuropathy' and 'R42 Leber hereditary optic neuropathy'.

The content of this panel is overseen by NHS Genomic Medicine Service governance. In addition to the evidence for a gene:disease association, this requires consideration of technical aspects of the assay(s) available.

CNVs, STRs and genes encoded by the mitochondrial genome may not be routinely included in the analysis where the panel is NOT delivered by WGS. Please contact your Genomic Laboratory Hub for information regarding specific queries.

Some of the genes in this panel cause conditions that typically present in adulthood. Please consider this when applying the panel.

This panel was originally developed for the 100,000 Genomes Project and is still being used for participants in the project. For the rare disease eligibility criteria refer to: https://www.genomicsengland.co.uk/rarediseasecriteria100K


The content of this panel (version 2.0: https://panelapp.genomicsengland.co.uk/api/v1/panels/186/?version=2.0) was signed off under NHS Genomic Medicine Service governance on (02/10/2019).

This panel will continue to be curated. New changes will be reflected in an increase to the minor version of the panel and details of these can be viewed in the 'Panel Activity' page. Periodically, these changes will be reviewed by a NHS Genomic Medicine Service evaluation process for the GMS panels.

8 reviewers

  • Ellen McDonagh (Genomics England Curator)

    Group: other
    Workplace: other

  • Tom Cullup (Great Ormond Street Hospital)

    Group: NHS Genomic Medicine Centre
    Workplace: NHS diagnostic lab

  • Ellen Thomas (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Sarah Leigh (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Panagiotis Sergouniotis (Academic Clinic Fellow)

    Group: GeCIP domain
    Workplace: NHS clinical service

  • Louise Daugherty (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Anna de Burca (Genomics England Curator)

    Group: NHS Genomic Medicine Centre
    Workplace: NHS clinical service

  • Ivone Leong (Genomics England Curator)

    Group: Other
    Workplace: Other

48 Entities

48 reviewed, 21 green

List Entity Reviews Mode of inheritance Details
48 Entitiess
Green Green List (high evidence)
ACO2
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • London North GLH
  • Other
Phenotypes
  • Optic atrophy 9
  • 616289
  • optic atrophy, nystagmus
  • Infantile cerebellar-retinal degeneration
Tags
Green Green List (high evidence)
C12orf65
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • London North GLH
Phenotypes
  • SPASTIC PARAPLEGIA 55, AUTOSOMAL RECESSIVE, 615035
Tags
Green Green List (high evidence)
C19orf12
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • London North GLH
Phenotypes
  • SPASTIC PARAPLEGIA 43, AUTOSOMAL RECESSIVE, 615043
  • NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 4, 614298
Tags
Green Green List (high evidence)
CISD2
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • London North GLH
Phenotypes
  • WOLFRAM SYNDROME 2, 604928
Tags
Green Green List (high evidence)
DNM1L
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • London North GLH
Phenotypes
  • OPTIC ATROPHY 5, 610708
Tags
Green Green List (high evidence)
MFF
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • London North GLH
Phenotypes
  • Encephalopathy due to defective mitochondrial and peroxisomal fission 2, 617086
Tags
Green Green List (high evidence)
MFN2
5 reviews
2 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert
  • Expert Review Green
  • London North GLH
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
Tags
Green Green List (high evidence)
MT-ATP6
2 reviews
1 green
MITOCHONDRIAL
Sources
  • Expert Review Green
  • London North GLH
  • UKGTN
Phenotypes
  • Leber optic atrophy
  • 535000
  • neurogenic weakness, ataxia, and retinitis pigmentosa
  • retinopathy
Tags
Green Green List (high evidence)
MT-ND1
2 reviews
1 green
MITOCHONDRIAL
Sources
  • Expert Review Green
  • London North GLH
  • UKGTN
Phenotypes
  • Optic neuropathy and nystagmus
  • External ophthalmoplegia
  • Leber's hereditary optic neuropathy
Tags
Green Green List (high evidence)
MT-ND4
3 reviews
1 green
MITOCHONDRIAL
Sources
  • Expert Review Green
  • London North GLH
  • UKGTN
Phenotypes
  • Leber's hereditary optic neuropathy
Tags
  • gene-therapy-trial
Green Green List (high evidence)
MT-ND6
3 reviews
1 green
MITOCHONDRIAL
Sources
  • Expert Review Green
  • London North GLH
  • UKGTN
Phenotypes
  • Leber hereditary optic neuropathy
  • Nystagmus
  • severe infantile-onset complex I deficiency
Tags
Green Green List (high evidence)
NR2F1
3 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • London North GLH
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Bosch-Boonstra-Schaaf optic atrophy syndrome, 615722
Tags
Green Green List (high evidence)
OPA1
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Emory Genetics Laboratory
  • Expert
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • London North GLH
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Optic atrophy 1 165500
  • Optic atrophy plus syndrome 125250
Tags
Green Green List (high evidence)
OPA3
4 reviews
2 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • London North GLH
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Autosomal Dominant Optic Atrophy
  • optic atrophy and cataracts
  • Optic atrophy 3 with cataract
Tags
Green Green List (high evidence)
RTN4IP1
3 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
  • London North GLH
Phenotypes
  • early-onset recessive optic neuropathy
Tags
Green Green List (high evidence)
SLC25A46
2 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
  • London North GLH
Phenotypes
  • Neuropathy, hereditary motor and sensory, type VIB 616505
Tags
Green Green List (high evidence)
SLC52A2
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • London North GLH
  • Other
Phenotypes
  • Brown-Vialetto-Van Laere syndrome 2, 614707
Tags
  • treatable
Green Green List (high evidence)
SPG7
4 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert
  • Expert Review Green
  • London North GLH
Phenotypes
  • SPASTIC PARAPLEGIA 7, AUTOSOMAL RECESSIVE, 607259
Tags
Green Green List (high evidence)
SSBP1
2 reviews
2 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert list
  • Expert Review Green
Phenotypes
  • Autosomal dominant optic atrophy with variable retinal degeneration
Tags
Green Green List (high evidence)
TMEM126A
4 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Emory Genetics Laboratory
  • Expert
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • London North GLH
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Optic Atrophy, Recessive
  • Optic atrophy 7, 612989
Tags
  • founder-effect
Green Green List (high evidence)
WFS1
3 reviews
1 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert
  • Expert Review Green
  • London North GLH
Phenotypes
  • Wolfram syndrome
Tags
Amber Amber List (moderate evidence)
AFG3L2
1 review
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • London North GLH
Phenotypes
  • SPASTIC ATAXIA 5, AUTOSOMAL RECESSIVE, 614487
  • SPINOCEREBELLAR ATAXIA 28, 610246
Tags
Amber Amber List (moderate evidence)
POLG
1 review
1 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • London North GLH
Phenotypes
  • PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL DOMINANT 1, 157640
  • PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE 1, 258450
Tags
Amber Amber List (moderate evidence)
TIMM8A
4 reviews
1 green
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Emory Genetics Laboratory
  • Expert Review Amber
  • London North GLH
Phenotypes
  • deafness-dystonia-optic neuropathy syndrome
  • Mohr-Tranebjaerg syndrome
Tags
Red Red List (low evidence)
ALG3
1 review
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • London North GLH
Phenotypes
  • CONGENITAL DISORDER OF GLYCOSYLATION, TYPE Id, 601110
Tags
Red Red List (low evidence)
ATAD3A
1 review
1 red
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • London North GLH
Phenotypes
  • Harel-Yoon syndrome: optic atrophy, peripheral neuropathy, delayed psychomotor development, intellectual disability, spastic paraplegia (HAYOS), 617183
Tags
Red Red List (low evidence)
AUH
1 review
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • London North GLH
Phenotypes
  • 3-METHYLGLUTACONIC ACIDURIA, TYPE I, 250950
Tags
Red Red List (low evidence)
DNAJC19
1 review
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • London North GLH
Phenotypes
  • 3-METHYLGLUTACONIC ACIDURIA, TYPE V, 610198
Tags
Red Red List (low evidence)
FXN
1 review
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • London North GLH
Phenotypes
  • Friedreich ataxia (FRDA), 229300
Tags
Red Red List (low evidence)
GP1BA
2 reviews
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • London North GLH
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • {Nonarteritic anterior ischemic optic neuropathy, susceptibility to}
Tags
Red Red List (low evidence)
KIF7
1 review
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • London North GLH
Phenotypes
  • ACROCALLOSAL SYNDROME, 200990
Tags
Red Red List (low evidence)
LYST
2 reviews
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • Literature
  • London North GLH
Phenotypes
  • Optic neuropathy in late-onset neurodegenerative Chédiak–Higashi syndrome lacking features of ocular albinism
Tags
Red Red List (low evidence)
MTPAP
1 review
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • London North GLH
Phenotypes
  • SPASTIC ATAXIA 4, AUTOSOMAL RECESSIVE, 613672
Tags
Red Red List (low evidence)
NDUFS1
1 review
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • London North GLH
Phenotypes
  • MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 5, 618226
Tags
Red Red List (low evidence)
NDUFS2
1 review
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • London North GLH
Phenotypes
  • Mitochondrial complex I deficiency, nuclear type 6, 618228
Tags
Red Red List (low evidence)
NDUFS3
1 review
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • London North GLH
Phenotypes
  • Mitochondrial complex I deficiency, nuclear type 8, 618230
Tags
Red Red List (low evidence)
NEFH
1 review
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • London North GLH
Phenotypes
  • CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2CC, 616924
Tags
Red Red List (low evidence)
RAB3GAP1
1 review
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • London North GLH
Phenotypes
  • WARBURG MICRO SYNDROME 1, 600118
Tags
Red Red List (low evidence)
SDHA
1 review
1 red
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • London North GLH
Phenotypes
  • Leigh syndrome, 256000
  • mitochondrial respiratory chain complex II deficiency 252011
Tags
Red Red List (low evidence)
TBC1D20
1 review
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • London North GLH
Phenotypes
  • WARBURG MICRO SYNDROME 4 615663
Tags
Red Red List (low evidence)
TSFM
1 review
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • London North GLH
Phenotypes
  • COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 3, 610505
Tags
Red Red List (low evidence)
YME1L1
1 review
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • London North GLH
Phenotypes
  • Optic atrophy 617302
  • sensorineural hearing impairment
  • ataxia
  • other CNS symptoms (OPA11)
Tags
Red Red List (low evidence)
ZNHIT3
1 review
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • London North GLH
Phenotypes
  • Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO) 260565
Tags
No list No list
OPA2
2 reviews
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Expert Review Removed
  • Other
Phenotypes
  • Optic atrophy 2, X-linked
Tags
  • locus-type-phenotype-only
No list No list
OPA4
2 reviews
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Removed
  • Other
Phenotypes
  • Optic atrophy 4
Tags
  • locus-type-phenotype-only
No list No list
OPA5
2 reviews
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Removed
  • Other
Phenotypes
  • Optic atrophy 5
Tags
  • locus-type-phenotype-only
No list No list
OPA6
2 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Removed
  • Other
Phenotypes
  • Optic atrophy 6
Tags
  • locus-type-phenotype-only
No list No list
OPA8
2 reviews
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Removed
  • Other
Phenotypes
  • Optic atrophy 8
  • 616648
Tags
  • locus-type-phenotype-only

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