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Pneumothorax - familial v1.8 ACTA2 Louise Daugherty gene: ACTA2 was added
gene: ACTA2 was added to Pneumothorax - familial. Sources: NHS GMS
Mode of inheritance for gene: ACTA2 was set to
Early onset or syndromic epilepsy v0.1460 GNAQ Sarah Leigh Marked gene: GNAQ as ready
Early onset or syndromic epilepsy v0.1460 GNAQ Sarah Leigh Added comment: Comment when marking as ready: Associated with phenotype in OMIM and not in Gen2Phen. At least one variant (rs397514698) was identified in at least 12/15 cases of Sturge-Weber syndrome, somatic, mosaic, 185300 (PMID 25374402). The percentage of the gain of function variant in brain tissues of these 12 patients ranged from 3.6 to 8.9%.
Early onset or syndromic epilepsy v0.1460 GNAQ Sarah Leigh Gene: gnaq has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1460 GNAQ Sarah Leigh Classified gene: GNAQ as Green List (high evidence)
Early onset or syndromic epilepsy v0.1460 GNAQ Sarah Leigh Gene: gnaq has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1459 AIMP1 Rebecca Foulger Added comment: Comment on mode of inheritance: Updated MOI from monoallelic to biallelic to match OMIM, Gene2Phenotype, and other relevant panels.
Early onset or syndromic epilepsy v0.1459 AIMP1 Rebecca Foulger Mode of inheritance for gene: AIMP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1458 GNAQ Sarah Leigh Publications for gene: GNAQ were set to
Early onset or syndromic epilepsy v0.1457 GRIN2D Konstantinos Varvagiannis reviewed gene: GRIN2D: Rating: GREEN; Mode of pathogenicity: None; Publications: 27616483, 30280376; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Pancreatitis v0.43 MORC4 Ellen McDonagh edited their review of gene: MORC4: Changed rating: RED
Pancreatitis v0.43 SPINK1 Ellen McDonagh commented on gene: SPINK1
Pancreatitis v0.43 PRSS1 Ellen McDonagh commented on gene: PRSS1
Pulmonary arterial hypertension v1.39 TBX4 Louise Daugherty edited their review of gene: TBX4: Added comment: Initial gene list and info collated by Ian Berry Leeds Genetics Laboratory November 2018 on behalf of the GMS Respiratory specialist test group. Gene Symbol submitted: TBX4; Suggested initial gene rating: Green; Evidence for inclusion: Small patella syndrome & PAH in children (PMID: 23592887 ); Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given; Changed rating: GREEN
Pulmonary arterial hypertension v1.39 SOX17 Louise Daugherty commented on gene: SOX17: Initial gene list and info collated by Ian Berry Leeds Genetics Laboratory November 2018 on behalf of the GMS Respiratory specialist test group. Gene Symbol submitted: SOX17; Suggested initial gene rating: Green; Evidence for inclusion: PMID:29650961. Graf et al (2018); PMID:30044643 & 30029678, de novo & segregation cases, emerging gene at recent PAH conferences, see PanelApp.; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given
Pulmonary arterial hypertension v1.39 SMAD9 Louise Daugherty commented on gene: SMAD9: Initial gene list and info collated by Ian Berry Leeds Genetics Laboratory November 2018 on behalf of the GMS Respiratory specialist test group. Gene Symbol submitted: SMAD9; Suggested initial gene rating: Green; Evidence for inclusion: OMIM PPH gene; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given
Pulmonary arterial hypertension v1.39 SARS2 Louise Daugherty reviewed gene: SARS2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pulmonary arterial hypertension v1.39 KCNK3 Louise Daugherty commented on gene: KCNK3: Initial gene list and info collated by Ian Berry Leeds Genetics Laboratory November 2018 on behalf of the GMS Respiratory specialist test group. Gene Symbol submitted: KCNK3; Suggested initial gene rating: Green; Evidence for inclusion: OMIM PPH gene; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given
Pulmonary arterial hypertension v1.39 GDF2 Louise Daugherty commented on gene: GDF2: Initial gene list and info collated by Ian Berry Leeds Genetics Laboratory November 2018 on behalf of the GMS Respiratory specialist test group. Gene Symbol submitted: GDF2; Suggested initial gene rating: Green; Evidence for inclusion: HHT gene; some cases described w/ PAH; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given
Pulmonary arterial hypertension v1.39 ENG Louise Daugherty commented on gene: ENG: Initial gene list and info collated by Ian Berry Leeds Genetics Laboratory November 2018 on behalf of the GMS Respiratory specialist test group. Gene Symbol submitted: ENG; Suggested initial gene rating: Green; Evidence for inclusion: HHT gene; some cases described w/ PAH; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): Multiple promoter/UTR mutations, needs to be covered.
Pulmonary arterial hypertension v1.39 EIF2AK4 Louise Daugherty commented on gene: EIF2AK4: Initial gene list and info collated by Ian Berry Leeds Genetics Laboratory November 2018 on behalf of the GMS Respiratory specialist test group. Gene Symbol submitted: EIF2AK4; Suggested initial gene rating: Green; Evidence for inclusion: OMIM Pulmonary venoocclusive disease 2; causes PAH.; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given
Pulmonary arterial hypertension v1.39 CAV1 Louise Daugherty edited their review of gene: CAV1: Added comment: Initial gene list and info collated by Ian Berry Leeds Genetics Laboratory November 2018 on behalf of the GMS Respiratory specialist test group. Gene Symbol submitted: CAV1; Suggested initial gene rating: Green; Evidence for inclusion: OMIM PPH gene; Evidence for exclusion: Severe infantile syndrome, PAH unlikely to be presenting feature; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given; Changed rating: GREEN
Pulmonary arterial hypertension v1.39 BMPR2 Louise Daugherty commented on gene: BMPR2: Initial gene list and info collated by Ian Berry Leeds Genetics Laboratory November 2018 on behalf of the GMS Respiratory specialist test group. Gene Symbol submitted: BMPR2; Suggested initial gene rating: Green; Evidence for inclusion: OMIM PPH gene; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): Causative of majority of cases
Pulmonary arterial hypertension v1.39 ATP13A3 Louise Daugherty edited their review of gene: ATP13A3: Added comment: Initial gene list and info collated by Ian Berry Leeds Genetics Laboratory November 2018 on behalf of the GMS Respiratory specialist test group. Gene Symbol submitted: ATP13A3; Suggested initial gene rating: Amber; Evidence for inclusion: PMID: 29650961 Graf et al (2018), further evidence from BRIDGE study (see PanelApp); Evidence for exclusion: BRIDGE evidence not yet published; data in Graf et al. not yet convincing.; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given; Changed rating: AMBER
Pulmonary arterial hypertension v1.39 AQP1 Louise Daugherty commented on gene: AQP1: Initial gene list and info collated by Ian Berry Leeds Genetics Laboratory November 2018 on behalf of the GMS Respiratory specialist test group. Gene Symbol submitted: AQP1; Suggested initial gene rating: Amber; Evidence for inclusion: PMID: 29650961. Graf et al (2018); Evidence for exclusion: Only three families, no convincing functional evidence.; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given
Pulmonary arterial hypertension v1.39 ACVRL1 Louise Daugherty commented on gene: ACVRL1: Initial gene list and info collated by Ian Berry Leeds Genetics Laboratory November 2018 on behalf of the GMS Respiratory specialist test group. Gene Symbol submitted: ACVRL1; Suggested initial gene rating: Green; Evidence for inclusion: HHT gene; some cases described w/ PAH; Evidence for exclusion: none given; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given
Intellectual disability v2.576 GRIN2D Konstantinos Varvagiannis gene: GRIN2D was added
gene: GRIN2D was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: GRIN2D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: GRIN2D were set to 27616483; 30280376
Phenotypes for gene: GRIN2D were set to Epileptic encephalopathy, early infantile, 46 (MIM 617162)
Penetrance for gene: GRIN2D were set to unknown
Review for gene: GRIN2D was set to GREEN
gene: GRIN2D was marked as current diagnostic
Added comment: Heterozygous pathogenic variants in GRIN2D cause Epileptic encephalopathy, early infantile, 46 (MIM 617162).

As commented in the previous review, PMID: 27616483 is the first report on 2 unrelated individuals with severe epileptic encephalopathy (onset of seizures at the age of 2 and 4 months). Severe DD with ID was noted in both.

Each of these individuals were heterozygous for the same missense variant (NM_000836.2:c.1999G>A p.Val667Ile) as a de novo event. Functional studies demonstrated a gain-of-function effect.

GRIN2D encodes for an NMDA receptor subunit, and the gain-of-function effect shown for this variant suggests that NMDAR antagonists might be useful as adjuvant therapy (some improvement noted in both individuals).

[The mode of pathogenicity selected here may be modified as more evidence on further variants becomes available. GRIN2D appears to be intolerant also to LoF mutations with a pLI of 1. Both LoF and GoF mutations have been described for genes encoding other NMDAR subunits].

PMID: 30280376 reports on 3 additional unrelated patients with developmental and epileptic encephalopathy and pathogenic or likely pathogenic missense variants in GRIN2D.

Three additional missense variants are reported (Met681Ile, Ser694Arg, Asp449Asn). Parental studies were possible only for the patient with Met681Ile (de novo) as well as for the individual with Ser694Arg (only one parent available though).

Significant developmental delay was evident in all prior to the onset of seizures (1m/2y/3y respectively) and subsequent developmental stagnation/regression with ID.

The phenotype of these 3 individuals as well as of the 2 previously described is summarized in table 1 of the latter article.

GRIN2D is a probable DD gene in G2P and is included in gene panels for ID offered by diagnostic laboratories.

Several other genes for NMDA receptor subunits (eg. GRIN2A, GRIN2B, GRIN1) and relevant/similar phenotypes are included in this panel as green.

As a result, this gene can be considered for inclusion in the ID panel as green (or amber).
Sources: Literature
Pancreatitis v0.43 MORC4 Ellen McDonagh commented on gene: MORC4
Pancreatitis v0.43 MORC4 Ellen McDonagh gene: MORC4 was added
gene: MORC4 was added to Pancreatitis. Sources: Literature
Mode of inheritance for gene: MORC4 was set to Unknown
Publications for gene: MORC4 were set to 29884332; 29173301; 28754779; 26820620; 26784911; 26002935; 25253127; 23143602; 28754779; 24002981
Pancreatitis v0.42 CLDN2 Ellen McDonagh edited their review of gene: CLDN2: Changed rating: RED
Pancreatitis v0.42 CXCL8 Ellen McDonagh edited their review of gene: CXCL8: Added comment: In a publicaton search, could not find evidence for variants in this gene to be causative of pancreatitis.; Changed rating: RED
Pancreatitis v0.42 PRSS2 Ellen McDonagh Deleted their comment
Pancreatitis v0.42 CTSB Ellen McDonagh Added comment: Comment on publications: Polymorphisms in this gene have been associated with pancreatitis or tropical calcific pancreatitis, and the cathepsin B gene is involved in the pathology of pancreatitis (see publications). There does not seem to be enough evidence at this time for rare loss of function variants in this gene to be causative of hereditary pancreatitis.
Pancreatitis v0.42 CTSB Ellen McDonagh Publications for gene: CTSB were set to 30455353; 30134826; 29229780; 29079517; 27226576; 22580415; 19900452; 16492714; 10995788
Pulmonary arterial hypertension v1.38 TBX4 Louise Daugherty Source NHS GMS was added to TBX4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Pulmonary arterial hypertension v1.38 SOX17 Louise Daugherty Source NHS GMS was added to SOX17.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Pulmonary arterial hypertension v1.38 SMAD9 Louise Daugherty Source NHS GMS was added to SMAD9.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Pulmonary arterial hypertension v1.38 SARS2 Louise Daugherty gene: SARS2 was added
gene: SARS2 was added to Pulmonary arterial hypertension. Sources: NHS GMS
Mode of inheritance for gene: SARS2 was set to
Pulmonary arterial hypertension v1.38 KCNK3 Louise Daugherty Source NHS GMS was added to KCNK3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Pulmonary arterial hypertension v1.38 GDF2 Louise Daugherty Source NHS GMS was added to GDF2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Pulmonary arterial hypertension v1.38 ENG Louise Daugherty Source NHS GMS was added to ENG.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Pulmonary arterial hypertension v1.38 EIF2AK4 Louise Daugherty Source NHS GMS was added to EIF2AK4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Pulmonary arterial hypertension v1.38 CAV1 Louise Daugherty Source NHS GMS was added to CAV1.
Pulmonary arterial hypertension v1.38 BMPR2 Louise Daugherty Source NHS GMS was added to BMPR2.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Pulmonary arterial hypertension v1.38 ATP13A3 Louise Daugherty Source NHS GMS was added to ATP13A3.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Pulmonary arterial hypertension v1.38 AQP1 Louise Daugherty Source NHS GMS was added to AQP1.
Pulmonary arterial hypertension v1.38 ACVRL1 Louise Daugherty Source NHS GMS was added to ACVRL1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Pancreatitis v0.42 CTSB Ellen McDonagh edited their review of gene: CTSB: Changed rating: RED
Pancreatitis v0.42 CTSB Ellen McDonagh Added comment: Comment on publications: Polymorphisms in this gene have been associated with pancreatitis or tropical calcific pancreatitis, and the cathepsin B gene is involved in the pathology of pancreatitis (see publications). There does not seem to be enough evidence at this time for rare loss of function variants in this gene to be causative of hereditary pancreatitis.
Pancreatitis v0.42 CTSB Ellen McDonagh Publications for gene: CTSB were set to 30455353
Pancreatitis v0.41 CTSB Ellen McDonagh Added comment: Comment on publications: PMID: 30455353 - CTSC-deletion in mild and severe pancreatitis in vivo models was found to reduce the severity of pancreatitis compared to control mice.
Pancreatitis v0.41 CTSB Ellen McDonagh Publications for gene: CTSB were set to
Pancreatitis v0.40 CLDN2 Ellen McDonagh Publications for gene: CLDN2 were set to 29884332; 29173301; 28754779; 26820620; 26784911; 26002935; 25253127; 23143602; 28754779
Pancreatitis v0.39 CLDN2 Ellen McDonagh Publications for gene: CLDN2 were set to 29884332; 29173301; 28754779; 26820620; 26784911; 26002935; 25253127; 23143602
Limb disorders v0.351 ABL1 Eleanor Williams Classified gene: ABL1 as Amber List (moderate evidence)
Limb disorders v0.351 ABL1 Eleanor Williams Added comment: Comment on list classification: Downgraded to Amber on advice from Genomics England clinical team.
Limb disorders v0.351 ABL1 Eleanor Williams Gene: abl1 has been classified as Amber List (Moderate Evidence).
Pancreatitis v0.38 CLDN2 Ellen McDonagh Added comment: Comment on publications: Common polymorphisms at the CLDN2-MORC4 loci have been associated with chronic pancreatitis in numerous studies (see publications listed).
Pancreatitis v0.38 CLDN2 Ellen McDonagh Publications for gene: CLDN2 were set to
Early onset or syndromic epilepsy v0.1457 GNAQ Sarah Leigh Added comment: Comment on mode of pathogenicity: Somatic gain of function
Early onset or syndromic epilepsy v0.1457 GNAQ Sarah Leigh Mode of pathogenicity for gene: GNAQ was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Pancreatitis v0.37 CEL Ellen McDonagh edited their review of gene: CEL: Changed rating: RED
Early onset or syndromic epilepsy v0.1456 GNAQ Sarah Leigh Mode of inheritance for gene: GNAQ was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Pancreatitis v0.37 CEL Ellen McDonagh Publications for gene: CEL were set to 29233499
Pancreatitis v0.36 CEL Ellen McDonagh Added comment: Comment on publications: PMID: 29233499 - suggests CEL is an interesting candidate gene links to pancreatic disease; a recombined allele between CEL and its pseudogene CELP has been discovered which encodes a chimeric protein with impaired secretion increasing the risk for chronic pancreatitis five-fold.
Pancreatitis v0.36 CEL Ellen McDonagh Publications for gene: CEL were set to
Hereditary haemorrhagic telangiectasia v1.34 BMPR2 Louise Daugherty Source NHS GMS was added to BMPR2.
Hereditary haemorrhagic telangiectasia v1.34 GDF2 Louise Daugherty Source NHS GMS was added to GDF2.
Hereditary haemorrhagic telangiectasia v1.34 SMAD4 Louise Daugherty Source NHS GMS was added to SMAD4.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Hereditary haemorrhagic telangiectasia v1.34 ENG Louise Daugherty Source NHS GMS was added to ENG.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Hereditary haemorrhagic telangiectasia v1.34 ACVRL1 Louise Daugherty Source NHS GMS was added to ACVRL1.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v0.1455 NDUFS2 Eleanor Williams Marked gene: NDUFS2 as ready
Early onset or syndromic epilepsy v0.1455 NDUFS2 Eleanor Williams Gene: ndufs2 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1455 NDUFS2 Eleanor Williams Phenotypes for gene: NDUFS2 were changed from to Mitochondrial complex I deficiency 252010
Early onset or syndromic epilepsy v0.1454 NDUFS2 Eleanor Williams Publications for gene: NDUFS2 were set to
Early onset or syndromic epilepsy v0.1453 NDUFS2 Eleanor Williams Mode of inheritance for gene: NDUFS2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Pancreatitis v0.35 CCL2 Ellen McDonagh edited their review of gene: CCL2: Changed rating: RED
Early onset or syndromic epilepsy v0.1452 NDUFS2 Eleanor Williams Classified gene: NDUFS2 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v0.1452 NDUFS2 Eleanor Williams Added comment: Comment on list classification: Keep as Amber. Although there are sufficient cases to associate this gene with Mitochondrial complex I deficiency there is only 1 report of a patient with seizures.
Early onset or syndromic epilepsy v0.1452 NDUFS2 Eleanor Williams Gene: ndufs2 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1451 NDUFS2 Eleanor Williams commented on gene: NDUFS2
Pancreatitis v0.35 CCL2 Ellen McDonagh Added comment: Comment on publications: PMID: 23449669 - CCL2 knockout exacerbates chronic pancreatitis.
Pancreatitis v0.35 CCL2 Ellen McDonagh Publications for gene: CCL2 were set to
Pancreatitis v0.34 PRSS2 Ellen McDonagh commented on gene: PRSS2: Could not find evidence for an association with inherited pancreatitis.
Early onset or syndromic epilepsy v0.1451 GNAQ Sarah Leigh Phenotypes for gene: GNAQ were changed from to Sturge-Weber syndrome, somatic, mosaic, 185300
Pancreatitis v0.34 PRSS2 Ellen McDonagh edited their review of gene: PRSS2: Changed rating: RED
Pancreatitis v0.34 CTRC Ellen McDonagh Classified gene: CTRC as Amber List (moderate evidence)
Pancreatitis v0.34 CTRC Ellen McDonagh Added comment: Comment on list classification: Demoting this gene from Green to Amber as it seems to be a susceptibility gene, rather than an isolated cause of inherited pancreatitis.
Pancreatitis v0.34 CTRC Ellen McDonagh Gene: ctrc has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1450 GFM1 Sarah Leigh Classified gene: GFM1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1450 GFM1 Sarah Leigh Gene: gfm1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1449 GFM1 Sarah Leigh Marked gene: GFM1 as ready
Early onset or syndromic epilepsy v0.1449 GFM1 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least five variants reported in at least three unrelated cases in which seizures are a phenotypic feature.
Early onset or syndromic epilepsy v0.1449 GFM1 Sarah Leigh Gene: gfm1 has been classified as Amber List (Moderate Evidence).
Pancreatitis v0.31 PRSS2 Ellen McDonagh Added comment: Comment on publications: PMID: 16699518 - the G191R variant in this gene is deemed protective against chronic pancreatitis.
Pancreatitis v0.31 PRSS2 Ellen McDonagh Publications for gene: PRSS2 were set to 25253127; 23143602; 27846138; 26784911; 26002935; 26110235; 29884332; 19052022; 15776435; 16699518; 14695529
Pancreatitis v0.30 PRSS2 Ellen McDonagh Phenotypes for gene: PRSS2 were changed from to {Pancreatitis, chronic, protection against} 167800
Early onset or syndromic epilepsy v0.1449 GFM1 Sarah Leigh Mode of inheritance for gene: GFM1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1448 GFM1 Sarah Leigh Phenotypes for gene: GFM1 were changed from to Combined oxidative phosphorylation deficiency 1 609060
Pancreatitis v0.29 PRSS2 Ellen McDonagh Added comment: Comment on publications: PMID: 14695529 - a mutation in PRSS1 causes increased transactivation of PRSS2.
Pancreatitis v0.29 PRSS2 Ellen McDonagh Publications for gene: PRSS2 were set to 25253127; 23143602; 27846138; 26784911; 26002935; 26110235; 29884332; 19052022; 15776435; 16699518; 18362849; 14695529
Pancreatitis v0.29 PRSS2 Ellen McDonagh Added comment: Comment on publications: PMID: 14695529 - a mutation in PRSS1 causes increased transactivation of PRSS2.
Pancreatitis v0.29 PRSS2 Ellen McDonagh Publications for gene: PRSS2 were set to 25253127; 23143602; 27846138; 26784911; 26002935; 26110235; 29884332; 19052022; 15776435; 16699518
Pancreatitis v0.28 PRSS2 Ellen McDonagh Added comment: Comment on publications: Multiple association studies for PRSS1-PRSS2 locus and chronic pancreatitis, tropical calfific pancreatitis, acute pancreatitis, alcoholic and non-alcoholic pancreatitis, sporadic pancreatitis.
Pancreatitis v0.28 PRSS2 Ellen McDonagh Publications for gene: PRSS2 were set to
Hereditary haemorrhagic telangiectasia v1.33 BMPR2 Louise Daugherty Classified gene: BMPR2 as Red List (low evidence)
Hereditary haemorrhagic telangiectasia v1.33 BMPR2 Louise Daugherty Gene: bmpr2 has been classified as Red List (Low Evidence).
Early onset or syndromic epilepsy v0.1447 GFM1 Sarah Leigh Publications for gene: GFM1 were set to
Pancreatitis v0.27 CXCL8 Ellen McDonagh commented on gene: CXCL8
Pancreatitis v0.27 CTSB Ellen McDonagh commented on gene: CTSB
Early onset or syndromic epilepsy v0.1446 DPM2 Sarah Leigh Phenotypes for gene: DPM2 were changed from to Congenital disorder of glycosylation, type Iu 615042
Early onset or syndromic epilepsy v0.1445 DPM2 Sarah Leigh Publications for gene: DPM2 were set to
Pancreatitis v0.27 CASR Ellen McDonagh commented on gene: CASR: Variants in this gene seem to be a possible risk factor, unclear currently whether variants in this gene in isolation are causative of pancreatitis.
Early onset or syndromic epilepsy v0.1444 DPM2 Sarah Leigh Mode of inheritance for gene: DPM2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Pancreatitis v0.27 CASR Ellen McDonagh Added comment: Comment on publications: PMID: 26166472 - Overrepresentation of Rare CASR Coding Variants in a Sample of Young French Patients With Idiopathic Chronic Pancreatitis. PMID: 18680227 - case-control study in 57 patients and 21 controls found the R990G polymorphism was significantly associated with chronic pancreatitis (OR, 2.01; 95% CI, 1.12-3.59; P = 0.015).
Pancreatitis v0.27 CASR Ellen McDonagh Publications for gene: CASR were set to 29173301; 17853337
Early onset or syndromic epilepsy v0.1443 COX15 Sarah Leigh Mode of inheritance for gene: COX15 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1442 COX15 Sarah Leigh Phenotypes for gene: COX15 were changed from to Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2 615119; Leigh syndrome 256000
Early onset or syndromic epilepsy v0.1441 COX15 Sarah Leigh Publications for gene: COX15 were set to
Pancreatitis v0.26 CASR Ellen McDonagh Added comment: Comment on publications: PMID: 29173301 - 5 children with variants in this gene with acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP) were identified in next-generation sequencing of 10 genes, but unclear from the abstract whether these were considered diagnostic.
PMID: 17853337 - CASR gene was examined in patients with pancreatitis in primary hyperparathyroidism and no assoication with variants in this gene was found.
Pancreatitis v0.26 CASR Ellen McDonagh Publications for gene: CASR were set to
Early onset or syndromic epilepsy v0.1440 COG6 Sarah Leigh Mode of inheritance for gene: COG6 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1439 COG6 Sarah Leigh Added comment: Comment on phenotypes: Congenital disorder of glycosylation, type Iil 614576
Early onset or syndromic epilepsy v0.1439 COG6 Sarah Leigh Phenotypes for gene: COG6 were changed from to Congenital disorder of glycosylation, type Iil 614576
Early onset or syndromic epilepsy v0.1438 CNPY3 Sarah Leigh Marked gene: CNPY3 as ready
Early onset or syndromic epilepsy v0.1438 CNPY3 Sarah Leigh Added comment: Comment when marking as ready: Associated with phenotype in OMIM and not in Gen2Phen. At least three variants identified in two unrelated cases.
Early onset or syndromic epilepsy v0.1438 CNPY3 Sarah Leigh Gene: cnpy3 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1438 CNPY3 Sarah Leigh Tag watchlist tag was added to gene: CNPY3.
Early onset or syndromic epilepsy v0.1438 CNPY3 Sarah Leigh Publications for gene: CNPY3 were set to
Early onset or syndromic epilepsy v0.1437 CNPY3 Sarah Leigh Mode of inheritance for gene: CNPY3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1436 CNPY3 Sarah Leigh Phenotypes for gene: CNPY3 were changed from to Epileptic encephalopathy, early infantile, 60 617929
Pancreatitis v0.25 CTRB1 Ellen McDonagh edited their review of gene: CTRB1: Changed rating: RED
Hereditary haemorrhagic telangiectasia v1.32 BMPR2 Louise Daugherty reviewed gene: BMPR2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary haemorrhagic telangiectasia v1.32 GDF2 Louise Daugherty reviewed gene: GDF2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary haemorrhagic telangiectasia v1.32 SMAD4 Louise Daugherty reviewed gene: SMAD4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary haemorrhagic telangiectasia v1.32 ENG Louise Daugherty reviewed gene: ENG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary haemorrhagic telangiectasia v1.32 ACVRL1 Louise Daugherty reviewed gene: ACVRL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Pancreatitis v0.25 CTRB1 Ellen McDonagh Added comment: Comment on publications: PMID: 30076839 - an induced pancreatitis in vivo model revealed that CTRB1-deficient mice given cerulein had significant increases in intrapancreatic trypsin activity and developed more severe pancreatitis compared with control mice. The authors suggest that CTRB1 protects against secretagogue-induced pancreatitis by reducing trypsin activity.
Pancreatitis v0.25 CTRB1 Ellen McDonagh Publications for gene: CTRB1 were set to 28754779; 28951524
Hereditary haemorrhagic telangiectasia v1.31 BMPR2 Louise Daugherty gene: BMPR2 was added
gene: BMPR2 was added to Hereditary haemorrhagic telangiectasia. Sources:
Mode of inheritance for gene: BMPR2 was set to
Early onset or syndromic epilepsy v0.1435 NDUFV1 Sarah Leigh Marked gene: NDUFV1 as ready
Early onset or syndromic epilepsy v0.1435 NDUFV1 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least six variants reported in at least three unrelated cases in which seizures are a phenotypic feature.
Early onset or syndromic epilepsy v0.1435 NDUFV1 Sarah Leigh Gene: ndufv1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1435 NDUFV1 Sarah Leigh Classified gene: NDUFV1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1435 NDUFV1 Sarah Leigh Added comment: Comment on list classification: Sufficient variants in unrelated cases displaying seizures.
Early onset or syndromic epilepsy v0.1435 NDUFV1 Sarah Leigh Gene: ndufv1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1434 NDUFV1 Sarah Leigh Mode of inheritance for gene: NDUFV1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1433 NDUFV1 Sarah Leigh Phenotypes for gene: NDUFV1 were changed from to Mitochondrial complex I deficiency 252010
Pancreatitis v0.24 CTRB1 Ellen McDonagh Publications for gene: CTRB1 were set to
Pancreatitis v0.23 CTRB1 Ellen McDonagh commented on gene: CTRB1: PMID: 28754779 - identified CTRB1-CTRB2 as a new risk locus for alcoholic chronic pancreatitis and non-alcoholic chronic pancreatitis. A 16.6 kb inversion in the CTRB1-CTRB2 locus was in linkage disequilibrium with the CP-associated SNPs and was best tagged by rs8048956, reported to changes the expression ratio of the CTRB1 and CTRB2 isoforms and thereby affects protective trypsinogen degradation and ultimately pancreatitis risk. PMID: 28951524 found no association in the Chinese population. Not enough evidence at this time for this to be a cause of monogenic pancreatitis.
Pancreatitis v0.23 CTRB2 Ellen McDonagh Phenotypes for gene: CTRB2 were changed from to risk factor for alcoholic and non-alcoholic chronic pancreatitis
Pancreatitis v0.22 CTRB2 Ellen McDonagh Publications for gene: CTRB2 were set to
Pancreatitis v0.21 CTRB2 Ellen McDonagh reviewed gene: CTRB2: Rating: RED; Mode of pathogenicity: None; Publications: 28754779, 28951524; Phenotypes: risk factor for alcoholic/non-alcoholic chronic pancreatitis; Mode of inheritance: None
Early onset or syndromic epilepsy v0.1432 NDUFV1 Sarah Leigh Publications for gene: NDUFV1 were set to
Pancreatitis v0.21 CTRB1 Ellen McDonagh commented on gene: CTRB1
Pancreatitis v0.21 CLDN2 Ellen McDonagh commented on gene: CLDN2
Pancreatitis v0.21 CEL Ellen McDonagh commented on gene: CEL
Pancreatitis v0.21 CCL2 Ellen McDonagh commented on gene: CCL2
Pancreatitis v0.21 CASR Ellen McDonagh reviewed gene: CASR: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early onset or syndromic epilepsy v0.1431 NDUFV1 Eleanor Williams reviewed gene: NDUFV1: Rating: ; Mode of pathogenicity: None; Publications: 25615419; Phenotypes: ; Mode of inheritance: None
Early onset or syndromic epilepsy v0.1431 COG8 Sarah Leigh Phenotypes for gene: COG8 were changed from to Congenital disorder of glycosylation, type IIh 611182
Early onset or syndromic epilepsy v0.1430 COG8 Sarah Leigh Publications for gene: COG8 were set to
Early onset or syndromic epilepsy v0.1429 COG8 Sarah Leigh Mode of inheritance for gene: COG8 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1428 NDUFS1 Eleanor Williams Marked gene: NDUFS1 as ready
Early onset or syndromic epilepsy v0.1428 NDUFS1 Eleanor Williams Gene: ndufs1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1428 MAP2K2 Sarah Leigh Mode of inheritance for gene: MAP2K2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v0.1427 NDUFS1 Eleanor Williams Phenotypes for gene: NDUFS1 were changed from to Mitochondrial complex I deficiency, 252010; LEIGH SYNDROME; MITOCHONDRIAL RESPIRATORY CHAIN COMPLEX I DEFICIENCY
Early onset or syndromic epilepsy v0.1426 NDUFS1 Eleanor Williams Mode of inheritance for gene: NDUFS1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1425 NDUFS1 Eleanor Williams Publications for gene: NDUFS1 were set to
Early onset or syndromic epilepsy v0.1424 NDUFS1 Eleanor Williams Classified gene: NDUFS1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v0.1424 NDUFS1 Eleanor Williams Added comment: Comment on list classification: Keeping this gene amber on this panel, because although there are enough cases to associate the gene with the disease possible epilepsy/seizures have only been observed in 2 cases.
Early onset or syndromic epilepsy v0.1424 NDUFS1 Eleanor Williams Gene: ndufs1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1423 NDUFS1 Eleanor Williams commented on gene: NDUFS1
Early onset or syndromic epilepsy v0.1423 SCO2 Sarah Leigh Marked gene: SCO2 as ready
Early onset or syndromic epilepsy v0.1423 SCO2 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least four variants reported as compound heterozygotes in three unrelated cases of Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1, 604377 in which seizures were a phenotypic feature. It appears from the literature that seizures are not commonly reported in this phenotype (PMIDs 14994243, 12020273).
Early onset or syndromic epilepsy v0.1423 SCO2 Sarah Leigh Gene: sco2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1423 SCO2 Sarah Leigh Classified gene: SCO2 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1423 SCO2 Sarah Leigh Gene: sco2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1422 NDUFAF5 Eleanor Williams Marked gene: NDUFAF5 as ready
Early onset or syndromic epilepsy v0.1422 NDUFAF5 Eleanor Williams Gene: ndufaf5 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1422 SCO2 Sarah Leigh Publications for gene: SCO2 were set to 10545952; 10749987
Early onset or syndromic epilepsy v0.1421 NDUFAF5 Eleanor Williams Phenotypes for gene: NDUFAF5 were changed from to Mitochondrial complex 1 deficiency 252010
Early onset or syndromic epilepsy v0.1420 NDUFAF5 Eleanor Williams Publications for gene: NDUFAF5 were set to
Early onset or syndromic epilepsy v0.1419 NDUFAF5 Eleanor Williams Mode of inheritance for gene: NDUFAF5 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1418 NDUFAF5 Eleanor Williams Classified gene: NDUFAF5 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1418 NDUFAF5 Eleanor Williams Added comment: Comment on list classification: Variants in this gene reported in more than 3 families with affected individuals. Seizures seen in 5 families.
Early onset or syndromic epilepsy v0.1418 NDUFAF5 Eleanor Williams Gene: ndufaf5 has been classified as Green List (High Evidence).
DDG2P v0.18 SAMD9 Rebecca Foulger commented on gene: SAMD9
DDG2P v0.18 LRRC56 Rebecca Foulger commented on gene: LRRC56
DDG2P v0.18 CACNA1E Rebecca Foulger commented on gene: CACNA1E
DDG2P v0.18 SAMD9 Rebecca Foulger gene: SAMD9 was added
gene: SAMD9 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: SAMD9 was set to
Publications for gene: SAMD9 were set to 28346228; 27182967
Phenotypes for gene: SAMD9 were set to MIRAGE - myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, enteropathy
DDG2P v0.18 LRRC56 Rebecca Foulger gene: LRRC56 was added
gene: LRRC56 was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: LRRC56 was set to
Phenotypes for gene: LRRC56 were set to Mucociliary Clearance and Laterality Defects
DDG2P v0.18 CACNA1E Rebecca Foulger gene: CACNA1E was added
gene: CACNA1E was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: CACNA1E was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CACNA1E were set to 30343943
Phenotypes for gene: CACNA1E were set to Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesia
Mode of pathogenicity for gene: CACNA1E was set to Other - please provide details in the comments
Hereditary ataxia v1.144 FMR1_CGG Louise Daugherty Classified STR: FMR1_CGG as No list
Hereditary ataxia v1.144 FMR1_CGG Louise Daugherty Added comment: Comment on list classification: Removed STR from Panel. This STR was not listed on the recent GMC STRs document supplied by Arianna Tucci.
Hereditary ataxia v1.144 FMR1_CGG Louise Daugherty Str: fmr1_cgg has been removed from the panel.
Primary ovarian insufficiency v1.14 FMR1_CGG Louise Daugherty Classified STR: FMR1_CGG as No list
Primary ovarian insufficiency v1.14 FMR1_CGG Louise Daugherty Added comment: Comment on list classification: Removed STR from Panel. This STR was not listed on the recent GMC STRs document supplied by Arianna Tucci.
Primary ovarian insufficiency v1.14 FMR1_CGG Louise Daugherty Str: fmr1_cgg has been removed from the panel.
Fetal anomalies v0.7 ATP1A3 Rebecca Foulger Deleted their comment
Fetal anomalies v0.7 ANO5 Rebecca Foulger Deleted their comment
Fetal anomalies v0.7 RET Rebecca Foulger Deleted their comment
Intellectual disability v2.575 C9orf72_GGGGCC Louise Daugherty Pathogenic Number of Repeats for C9orf72_GGGGCC was changed from 60 to 30.
Fetal anomalies v0.7 TIMM8A Rebecca Foulger reviewed gene: TIMM8A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.7 THAP1 Rebecca Foulger reviewed gene: THAP1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.7 TGFB2 Rebecca Foulger reviewed gene: TGFB2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.7 SYNE1 Rebecca Foulger reviewed gene: SYNE1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.7 SPTLC2 Rebecca Foulger commented on gene: SPTLC2: Rating in original PAGE file: 'both DD and IF' for NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE IC
Fetal anomalies v0.7 SNORD118 Rebecca Foulger reviewed gene: SNORD118: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.7 SMCHD1 Rebecca Foulger commented on gene: SMCHD1: Rating in original PAGE file: 'both DD and IF' for Isolated Arhinia/Bosma Arhinia syndrome
Fetal anomalies v0.7 SLC4A11 Rebecca Foulger reviewed gene: SLC4A11: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.7 SLC4A1 Rebecca Foulger commented on gene: SLC4A1: Rating in original PAGE file: 'both DD and IF' for RENAL TUBULAR ACIDOSIS, DISTAL, AD and RENAL TUBULAR ACIDOSIS, DISTAL, AR.
Fetal anomalies v0.7 RRM2B Rebecca Foulger reviewed gene: RRM2B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.7 RET Rebecca Foulger commented on gene: RET: Rating in original PAGE file: 'both DD and IF' for RENAL AGENESIS and MULTIPLE ENDOCRINE NEOPLASIA IIB.
Fetal anomalies v0.7 POLD1 Rebecca Foulger commented on gene: POLD1: Rating in original PAGE file: 'both DD and IF' for SUBCUTANEOUS LIPODYSTROPHY, DEAFNESS, MANDIBULAR HYPOPLASIA AND MALE HYPOGONADISM
Fetal anomalies v0.7 PLA2G6 Rebecca Foulger reviewed gene: PLA2G6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.7 PDCD10 Rebecca Foulger reviewed gene: PDCD10: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.7 NR5A1 Rebecca Foulger commented on gene: NR5A1: Rating in original PAGE file: 'both DD and IF' for 46XY SEX REVERSAL 3 and SPERMATOGENIC FAILURE 8.
Fetal anomalies v0.7 MYO7A Rebecca Foulger reviewed gene: MYO7A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.7 MYH8 Rebecca Foulger commented on gene: MYH8: Rating in original PAGE file: 'both DD and IF' for CARNEY COMPLEX VARIANT and DISTAL ARTHROGRYPOSIS TYPE.
Fetal anomalies v0.7 MYH6 Rebecca Foulger commented on gene: MYH6: Rating in original PAGE file: 'both DD and IF' for ATRIAL SEPTAL DEFECT TYPE 3, CARDIOMYOPATHY DILATED TYPE 1EE and CARDIOMYOPATHY FAMILIAL HYPERTROPHIC TYPE 14.
Fetal anomalies v0.7 LMNA Rebecca Foulger commented on gene: LMNA: Rating in original PAGE file: 'both DD and IF' for CARDIOMYOPATHY DILATED TYPE 1A, CARDIOMYOPATHY DILATED WITH HYPERGONADOTROPIC HYPOGONADISM, FAMILIAL PARTIAL LIPODYSTROPHY TYPE 2, CHARCOT-MARIE-TOOTH DISEASE TYPE 2B1, HUTCHINSON-GILFORD PROGERIA SYNDROME, MUSCULAR DYSTROPHY CONGENITAL LMNA-RELATED, MANDIBULOACRAL DYSPLASIA WITH TYPE A LIPODYSTROPHY, EMERY-DREIFUSS MUSCULAR DYSTROPHY TYPE 2, LIMB-GIRDLE MUSCULAR DYSTROPHY TYPE 1B, LETHAL TIGHT SKIN CONTRACTURE SYNDROME and HEART-HAND SYNDROME SLOVENIAN TYPE.
Fetal anomalies v0.7 LDB3 Rebecca Foulger commented on gene: LDB3: Rating in original PAGE file: 'both DD and IF' for LEFT VENTRICULAR NON-COMPACTION TYPE 3 and CARDIOMYOPATHY DILATED TYPE 1C and MYOPATHY MYOFIBRILLAR TYPE 4.
Fetal anomalies v0.7 KRIT1 Rebecca Foulger reviewed gene: KRIT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.7 KIT Rebecca Foulger reviewed gene: KIT: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.7 KCNE1 Rebecca Foulger commented on gene: KCNE1: Rating in original PAGE file: 'both DD and IF' for JERVELL AND LANGE-NIELSEN SYNDROME TYPE 2
Fetal anomalies v0.7 KARS Rebecca Foulger commented on gene: KARS: Rating in original PAGE file: 'both DD and IF' for both CHARCOT-MARIE-TOOTH DISEASE, RECESSIVE INTERMEDIATE, B and DEAFNESS, AUTOSOMAL RECESSIVE 89.
Fetal anomalies v0.7 HSPD1 Rebecca Foulger reviewed gene: HSPD1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.7 GBA Rebecca Foulger reviewed gene: GBA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.7 FAM161A Rebecca Foulger reviewed gene: FAM161A: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.7 DARS2 Rebecca Foulger reviewed gene: DARS2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.7 COL4A2 Rebecca Foulger commented on gene: COL4A2: Rating in original PAGE file: 'both DD and IF' for PORENCEPHALY 2
Fetal anomalies v0.7 COL4A1 Rebecca Foulger commented on gene: COL4A1: Rating in original PAGE file: 'both DD and IF' for PORENCEPHALY 1
Fetal anomalies v0.7 CLN6 Rebecca Foulger commented on gene: CLN6: Rating in original PAGE file: 'both DD and IF' for both CEROID LIPOFUSCINOSIS, NEURONAL, 6 and CEROID LIPOFUSCINOSIS, NEURONAL, KUFS TYPE, ADULT ONSET.
Fetal anomalies v0.7 CISD2 Rebecca Foulger reviewed gene: CISD2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.7 CDH1 Rebecca Foulger commented on gene: CDH1: Rating in original PAGE file: 'both DD and IF' for Blepharo-cheiro-dontic syndrome
Fetal anomalies v0.7 BRCA2 Rebecca Foulger reviewed gene: BRCA2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.7 BRCA1 Rebecca Foulger reviewed gene: BRCA1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.7 ATP1A3 Rebecca Foulger commented on gene: ATP1A3: Rating in original PAGE file: 'both DD and IF' for both RAPID-ONSET DYSTONIA-PARKINSONISM and ALTERNATING HEMIPLEGIA OF CHILDHOOD.
Fetal anomalies v0.7 ATP13A2 Rebecca Foulger reviewed gene: ATP13A2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.7 AR Rebecca Foulger commented on gene: AR: Rating in original PAGE file: 'both DD and IF' for both SPINAL AND BULBAR MUSCULAR ATROPHY and ANDROGEN INSENSITIVITY SYNDROME.
Fetal anomalies v0.7 ANO5 Rebecca Foulger commented on gene: ANO5: Rating in original PAGE file: 'both DD and IF' for both MIYOSHI MUSCULAR DYSTROPHY TYPE 3 and GNATHODIAPHYSEAL DYSPLASIA.
Fetal anomalies v0.7 AMER1 Rebecca Foulger reviewed gene: AMER1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.7 ALDOB Rebecca Foulger reviewed gene: ALDOB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.7 ALAD Rebecca Foulger commented on gene: ALAD: Rating in original PAGE file: 'both DD and IF' for ACUTE HEPATIC PORPHYRIA
Fetal anomalies v0.7 AIRE Rebecca Foulger reviewed gene: AIRE: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.7 AGXT Rebecca Foulger reviewed gene: AGXT: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.7 ACTA2 Rebecca Foulger commented on gene: ACTA2: Rating in original PAGE file: 'both DD and IF' for MOYAMOYA DISEASE 5 and AORTIC ANEURYSM, FAMILIAL THORACIC 6.
Fetal anomalies v0.7 ACADS Rebecca Foulger commented on gene: ACADS: Rating in original PAGE file: 'both DD and IF' for SHORT CHAIN ACYL-COA DEHYDROGENASE DEFICIENCY
Fetal anomalies v0.7 ABCD1 Rebecca Foulger reviewed gene: ABCD1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v0.6 RET Rebecca Foulger commented on gene: RET: Rating in original PAGE file: 'Both DD and IF' for RENAL AGENESIS and MULTIPLE ENDOCRINE NEOPLASIA IIB.
Fetal anomalies v0.6 ATP1A3 Rebecca Foulger commented on gene: ATP1A3: Rating in original PAGE file: 'Both DD and IF' for both RAPID-ONSET DYSTONIA-PARKINSONISM and ALTERNATING HEMIPLEGIA OF CHILDHOOD.
Fetal anomalies v0.6 ANO5 Rebecca Foulger commented on gene: ANO5: Rating in original PAGE file: 'Both DD and IF' for both MIYOSHI MUSCULAR DYSTROPHY TYPE 3 and GNATHODIAPHYSEAL DYSPLASIA.
Fetal anomalies v0.5 SMAD4 Rebecca Foulger commented on gene: SMAD4: Multiple ratings in original PAGE file: rated as confirmed for MYHRE SYNDROME. Rated as both DD and IF for: JUVENILE POLYPOSIS/HEREDITARY HEMORRHAGIC TELANGIECTASIA SYNDROME and JUVENILE POLYPOSIS SYNDROME.
Fetal anomalies v0.5 FMR1 Rebecca Foulger commented on gene: FMR1: Multiple ratings in original PAGE file: rated as confirmed for FRAGILE X SYNDROME. Rated as both DD and IF for: PREMATURE OVARIAN FAILURE SYNDROME TYPE 1 and FRAGILE X TREMOR/ATAXIA SYNDROME.
Intellectual disability v2.574 MCM3AP Konstantinos Varvagiannis gene: MCM3AP was added
gene: MCM3AP was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: MCM3AP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCM3AP were set to 24123876; 28633435; 28969388; 29982295
Phenotypes for gene: MCM3AP were set to Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development (MIM 618124)
Penetrance for gene: MCM3AP were set to Complete
Review for gene: MCM3AP was set to AMBER
gene: MCM3AP was marked as current diagnostic
Added comment: Biallelic mutations in MCM3AP cause Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development (MIM 618124).

All relevant publications [PMIDs: 24123876, 28633435 (first detailed description of a series of patients with functional studies), 28969388, 29982295) are summarized in OMIM.

Overall more than 18 patients from 10 families and at least 8 pathogenic variants have been reported.

Apart from abnormal motor development which may be associated with the sensorimotor neuropathy, intellectual disability was a feature in several individuals (although not a universal one).

Some patients were initially evaluated for their ID while investigations for the neuropathy may be conducted late (as evident in PMID: 28633435).

MCM3AP is included in gene panels for intellectual disability offered by diagnostic laboratories.

As a result, this gene can be considered for inclusion in the ID panel as amber or green (depending on its relevance to the specific panel).
Sources: Literature
Amyotrophic lateral sclerosis/motor neuron disease v1.25 NOP56_GGCCTG Arianna Tucci Repeated Sequence for NOP56_GGCCTG was changed from CAG to GGCCTG.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.36 NOP56_GGCCTG Arianna Tucci Repeated Sequence for NOP56_GGCCTG was changed from CAG to GGCCTG.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Amyotrophic lateral sclerosis/motor neuron disease v1.24 C9orf72_GGGGCC Arianna Tucci Pathogenic Number of Repeats for C9orf72_GGGGCC was changed from 60 to 30.
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.35 C9orf72_GGGGCC Arianna Tucci Pathogenic Number of Repeats for C9orf72_GGGGCC was changed from 60 to 30.
Parkinson Disease and Complex Parkinsonism v1.58 C9orf72_GGGGCC Arianna Tucci Pathogenic Number of Repeats for C9orf72_GGGGCC was changed from 60 to 30.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Intellectual disability v2.574 SET Konstantinos Varvagiannis reviewed gene: SET: Rating: GREEN; Mode of pathogenicity: None; Publications: 29688601, 25356899, 28135719; Phenotypes: Mental retardation, autosomal dominant 58 (MIM 618106); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Early onset or syndromic epilepsy v0.1417 NDUFAF5 Eleanor Williams commented on gene: NDUFAF5
Early onset or syndromic epilepsy v0.1417 NDUFAF3 Eleanor Williams Marked gene: NDUFAF3 as ready
Early onset or syndromic epilepsy v0.1417 NDUFAF3 Eleanor Williams Gene: ndufaf3 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1417 NDUFAF3 Eleanor Williams Phenotypes for gene: NDUFAF3 were changed from to Mitochondrial complex I deficiency 252010
Early onset or syndromic epilepsy v0.1416 NDUFAF3 Eleanor Williams Publications for gene: NDUFAF3 were set to
Early onset or syndromic epilepsy v0.1415 NDUFAF3 Eleanor Williams Mode of inheritance for gene: NDUFAF3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1414 NDUFAF3 Eleanor Williams Classified gene: NDUFAF3 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v0.1414 NDUFAF3 Eleanor Williams Added comment: Comment on list classification: There are 3 cases supporting the association of NDUFAF3 with Mitochondrial complex I deficiency, but only two cases with seizures to date so keeping this gene Amber until further cases verify the association with seizures.
Early onset or syndromic epilepsy v0.1414 NDUFAF3 Eleanor Williams Gene: ndufaf3 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1413 NDUFAF3 Eleanor Williams commented on gene: NDUFAF3
Brain channelopathy v1.42 TBP_CAG Louise Daugherty Tag STR tag was added to STR: TBP_CAG.
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.34 TBP_CAG Louise Daugherty Tag STR tag was added to STR: TBP_CAG.
Hereditary spastic paraplegia v1.95 TBP_CAG Louise Daugherty Tag STR tag was added to STR: TBP_CAG.
Early onset or syndromic epilepsy v0.1413 ATN1_CAG Louise Daugherty Tag STR tag was added to STR: ATN1_CAG.
Intellectual disability v2.574 PPP2R2B_CAG Louise Daugherty Classified STR: PPP2R2B_CAG as No list
Intellectual disability v2.574 PPP2R2B_CAG Louise Daugherty Added comment: Comment on list classification: Removed STR from Panel. This STR was not listed on the recent GMC STRs document supplied by Arianna Tucci.
Intellectual disability v2.574 PPP2R2B_CAG Louise Daugherty Str: ppp2r2b_cag has been removed from the panel.
Parkinson Disease and Complex Parkinsonism v1.57 PPP2R2B_CAG Louise Daugherty Tag STR tag was added to STR: PPP2R2B_CAG.
Hereditary spastic paraplegia v1.95 PPP2R2B_CAG Louise Daugherty Tag STR tag was added to STR: PPP2R2B_CAG.
Amyotrophic lateral sclerosis/motor neuron disease v1.23 NOP56_GGCCTG Louise Daugherty Tag STR tag was added to STR: NOP56_GGCCTG.
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.34 NOP56_GGCCTG Louise Daugherty Tag STR tag was added to STR: NOP56_GGCCTG.
Early onset dystonia v1.61 JPH3_CTG Louise Daugherty Repeated Sequence for JPH3_CTG was changed from CTG to CAG.
Early onset dystonia v1.60 JPH3_CTG Louise Daugherty Deleted their comment
Early onset or syndromic epilepsy v0.1413 PSAP Eleanor Williams Classified gene: PSAP as Green List (high evidence)
Early onset or syndromic epilepsy v0.1413 PSAP Eleanor Williams Added comment: Comment on list classification: Promoting to green after gaining access to PMID: 2514102 and confirming a second case of a patient showing seizures, which along with the mouse knockout model confirms the association with seizures. In addition there is a green expert review.
Early onset or syndromic epilepsy v0.1413 PSAP Eleanor Williams Gene: psap has been classified as Green List (High Evidence).
Early onset dystonia v1.60 JPH3_CTG Louise Daugherty commented on STR: JPH3_CTG
Early onset dystonia v1.60 JPH3_CTG Louise Daugherty Repeated Sequence for JPH3_CTG was changed from CAG to CTG.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Brain channelopathy v1.42 HTT_CAG Louise Daugherty Classified STR: HTT_CAG as No list
Brain channelopathy v1.42 HTT_CAG Louise Daugherty Added comment: Comment on list classification: Removed STR from Panel. This STR was not listed on the recent GMC STRs document supplied by Arianna Tucci.
Brain channelopathy v1.42 HTT_CAG Louise Daugherty Str: htt_cag has been removed from the panel.
Early onset dystonia v1.59 JPH3_CTG Louise Daugherty Tag STR tag was added to STR: JPH3_CTG.
Structural basal ganglia disorders v1.10 HTT_CAG Louise Daugherty Classified STR: HTT_CAG as No list
Structural basal ganglia disorders v1.10 HTT_CAG Louise Daugherty Added comment: Comment on list classification: Removed STR from Panel. This STR was not listed on the recent GMC STRs document supplied by Arianna Tucci.
Structural basal ganglia disorders v1.10 HTT_CAG Louise Daugherty Str: htt_cag has been removed from the panel.
Brain channelopathy v1.41 HTT_CAG Louise Daugherty Normal Number of Repeats for HTT_CAG was changed from 36 to 40.
Pathogenic Number of Repeats for HTT_CAG was changed from 36 to 40.
Structural basal ganglia disorders v1.9 HTT_CAG Louise Daugherty Normal Number of Repeats for HTT_CAG was changed from 36 to 40.
Pathogenic Number of Repeats for HTT_CAG was changed from 36 to 40.
Hereditary spastic paraplegia v1.95 HTT_CAG Louise Daugherty Tag STR tag was added to STR: HTT_CAG.
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.34 HTT_CAG Louise Daugherty Tag STR tag was added to STR: HTT_CAG.
Hereditary ataxia v1.143 HTT_CAG Louise Daugherty Tag STR tag was added to STR: HTT_CAG.
Intellectual disability v2.573 FXN_GAA Louise Daugherty Classified STR: FXN_GAA as No list
Intellectual disability v2.573 FXN_GAA Louise Daugherty Added comment: Comment on list classification: Removed STR from Panel. This STR was not listed on the recent GMC STRs document supplied by Arianna Tucci.
Intellectual disability v2.573 FXN_GAA Louise Daugherty Str: fxn_gaa has been removed from the panel.
Intellectual disability v2.572 FXN_GAA Louise Daugherty Normal Number of Repeats for FXN_GAA was changed from 33 to 44.
Hypertrophic cardiomyopathy v1.25 FXN_GAA Louise Daugherty Classified STR: FXN_GAA as No list
Hypertrophic cardiomyopathy v1.25 FXN_GAA Louise Daugherty Added comment: Comment on list classification: Removed STR from Panel. This STR was not listed on the recent GMC STRs document supplied by Arianna Tucci.
Hypertrophic cardiomyopathy v1.25 FXN_GAA Louise Daugherty Str: fxn_gaa has been removed from the panel.
Hypertrophic cardiomyopathy v1.24 FXN_GAA Louise Daugherty Normal Number of Repeats for FXN_GAA was changed from 33 to 44.
Hereditary spastic paraplegia v1.95 FXN_GAA Louise Daugherty Tag STR tag was added to STR: FXN_GAA.
Hereditary neuropathy v1.37 FXN_GAA Louise Daugherty Tag STR tag was added to STR: FXN_GAA.
Mitochondrial disorders v1.73 FXN_GAA Louise Daugherty Tag STR tag was added to STR: FXN_GAA.
Congenital muscular dystrophy v1.18 DMPK_CTG Louise Daugherty Tag STR tag was added to STR: DMPK_CTG.
Mitochondrial disorders v1.73 DMPK_CTG Louise Daugherty Tag STR tag was added to STR: DMPK_CTG.
Fetal hydrops v1.16 DMPK_CTG Louise Daugherty Normal Number of Repeats for DMPK_CTG was changed from 34 to 38.
Gastrointestinal neuromuscular disorders v1.9 DMPK_CTG Louise Daugherty Normal Number of Repeats for DMPK_CTG was changed from 34 to 38.
Paediatric motor neuronopathies v1.19 DMPK_CTG Louise Daugherty Normal Number of Repeats for DMPK_CTG was changed from 34 to 38.
Intellectual disability v2.571 CSTB_CCCCGCCCCGCG Louise Daugherty Classified STR: CSTB_CCCCGCCCCGCG as No list
Intellectual disability v2.571 CSTB_CCCCGCCCCGCG Louise Daugherty Added comment: Comment on list classification: Removed STR from Panel. This STR was not listed on the recent GMC STRs document supplied by Arianna Tucci.
Intellectual disability v2.571 CSTB_CCCCGCCCCGCG Louise Daugherty Str: cstb_ccccgccccgcg has been removed from the panel.
Early onset or syndromic epilepsy v0.1412 CSTB_CCCCGCCCCGCG Louise Daugherty Tag STR tag was added to STR: CSTB_CCCCGCCCCGCG.
Hereditary ataxia v1.143 CSTB_CCCCGCCCCGCG Louise Daugherty Tag STR tag was added to STR: CSTB_CCCCGCCCCGCG.
Brain channelopathy v1.40 CSTB_CCCCGCCCCGCG Louise Daugherty Tag STR tag was added to STR: CSTB_CCCCGCCCCGCG.
Intellectual disability v2.570 C9orf72_GGGGCC Louise Daugherty Classified STR: C9orf72_GGGGCC as No list
Intellectual disability v2.570 C9orf72_GGGGCC Louise Daugherty Added comment: Comment on list classification: Removed STR from Panel. This STR was not listed on the recent GMC STRs document supplied by Arianna Tucci.
Intellectual disability v2.570 C9orf72_GGGGCC Louise Daugherty Str: c9orf72_ggggcc has been removed from the panel.
Undiagnosed metabolic disorders v1.79 ATXN7_CAG Louise Daugherty Classified STR: ATXN7_CAG as No list
Undiagnosed metabolic disorders v1.79 ATXN7_CAG Louise Daugherty Added comment: Comment on list classification: Removed STR from Panel. This STR was not listed on the recent GMC STRs document supplied by Arianna Tucci.
Undiagnosed metabolic disorders v1.79 ATXN7_CAG Louise Daugherty Str: atxn7_cag has been removed from the panel.
Hereditary spastic paraplegia v1.95 ATXN7_CAG Louise Daugherty Tag STR tag was added to STR: ATXN7_CAG.
Hereditary spastic paraplegia v1.95 CACNA1A_CAG Louise Daugherty Tag STR tag was added to STR: CACNA1A_CAG.
Brain channelopathy v1.40 CACNA1A_CAG Louise Daugherty Tag STR tag was added to STR: CACNA1A_CAG.
Intellectual disability v2.569 ATXN3_CAG Louise Daugherty Classified STR: ATXN3_CAG as No list
Intellectual disability v2.569 ATXN3_CAG Louise Daugherty Added comment: Comment on list classification: Removed STR from Panel. This STR was not listed on the recent GMC STRs document supplied by Arianna Tucci.
Intellectual disability v2.569 ATXN3_CAG Louise Daugherty Str: atxn3_cag has been removed from the panel.
Hereditary neuropathy v1.37 ATXN3_CAG Louise Daugherty Tag STR tag was added to STR: ATXN3_CAG.
Hereditary spastic paraplegia v1.95 ATXN3_CAG Louise Daugherty Tag STR tag was added to STR: ATXN3_CAG.
Early onset dystonia v1.59 ATXN3_CAG Louise Daugherty Tag STR tag was added to STR: ATXN3_CAG.
Intellectual disability v2.568 ATXN2_CAG Louise Daugherty Classified STR: ATXN2_CAG as No list
Intellectual disability v2.568 ATXN2_CAG Louise Daugherty Added comment: Comment on list classification: Removed STR from Panel. This STR was not listed on the recent GMC STRs document supplied by Arianna Tucci.
Intellectual disability v2.568 ATXN2_CAG Louise Daugherty Str: atxn2_cag has been removed from the panel.
Amyotrophic lateral sclerosis/motor neuron disease v1.23 ATXN2_CAG Louise Daugherty Classified STR: ATXN2_CAG as No list
Amyotrophic lateral sclerosis/motor neuron disease v1.23 ATXN2_CAG Louise Daugherty Added comment: Comment on list classification: Removed STR from Panel. This STR was not listed on the recent GMC STRs document supplied by Arianna Tucci.
Amyotrophic lateral sclerosis/motor neuron disease v1.23 ATXN2_CAG Louise Daugherty Str: atxn2_cag has been removed from the panel.
Early onset dystonia v1.59 ATXN2_CAG Louise Daugherty Tag STR tag was added to STR: ATXN2_CAG.
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.34 ATXN2_CAG Louise Daugherty Tag STR tag was added to STR: ATXN2_CAG.
Hereditary spastic paraplegia v1.95 ATXN2_CAG Louise Daugherty Tag STR tag was added to STR: ATXN2_CAG.
Hereditary neuropathy v1.37 ATXN2_CAG Louise Daugherty Tag STR tag was added to STR: ATXN2_CAG.
Skeletal dysplasia v1.130 ATXN10_ATTCT Louise Daugherty Classified STR: ATXN10_ATTCT as No list
Skeletal dysplasia v1.130 ATXN10_ATTCT Louise Daugherty Added comment: Comment on list classification: Removed STR from Panel. This STR was not listed on the recent GMC STRs document supplied by Arianna Tucci.
Skeletal dysplasia v1.130 ATXN10_ATTCT Louise Daugherty Str: atxn10_attct has been removed from the panel.
Intellectual disability v2.567 ATXN10_ATTCT Louise Daugherty Classified STR: ATXN10_ATTCT as No list
Intellectual disability v2.567 ATXN10_ATTCT Louise Daugherty Added comment: Comment on list classification: Removed STR from Panel. This STR was not listed on the recent GMC STRs document supplied by Arianna Tucci.
Intellectual disability v2.567 ATXN10_ATTCT Louise Daugherty Str: atxn10_attct has been removed from the panel.
Early onset or syndromic epilepsy v0.1412 PSAP Eleanor Williams Added comment: Comment on phenotypes: Only added Combined SAP deficiency as a phenotype as evidence for seizures only found for this disorder.
Early onset or syndromic epilepsy v0.1412 PSAP Eleanor Williams Phenotypes for gene: PSAP were changed from to Combined SAP deficiency 611721
Early onset or syndromic epilepsy v0.1411 PSAP Eleanor Williams Publications for gene: PSAP were set to
Early onset dystonia v1.59 ATXN10_ATTCT Louise Daugherty Classified STR: ATXN10_ATTCT as No list
Early onset dystonia v1.59 ATXN10_ATTCT Louise Daugherty Added comment: Comment on list classification: Removed STR from Panel. This STR was not listed on the recent GMC STRs document supplied by Arianna Tucci.
Early onset dystonia v1.59 ATXN10_ATTCT Louise Daugherty Str: atxn10_attct has been removed from the panel.
Early onset or syndromic epilepsy v0.1410 PSAP Eleanor Williams Mode of inheritance for gene: PSAP was changed from to BIALLELIC, autosomal or pseudoautosomal
Thoracic dystrophies v1.3 ATXN10_ATTCT Louise Daugherty Classified STR: ATXN10_ATTCT as No list
Thoracic dystrophies v1.3 ATXN10_ATTCT Louise Daugherty Added comment: Comment on list classification: Removed STR from Panel. This STR was not listed on the recent GMC STRs document supplied by Arianna Tucci.
Thoracic dystrophies v1.3 ATXN10_ATTCT Louise Daugherty Str: atxn10_attct has been removed from the panel.
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.34 ATXN10_ATTCT Louise Daugherty Tag STR tag was added to STR: ATXN10_ATTCT.
Early onset or syndromic epilepsy v0.1409 CSTB_CCCCGCCCCGCG Arianna Tucci Marked STR: CSTB_CCCCGCCCCGCG as ready
Early onset or syndromic epilepsy v0.1409 CSTB_CCCCGCCCCGCG Arianna Tucci Str: cstb_ccccgccccgcg has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.95 ATXN10_ATTCT Louise Daugherty Tag STR tag was added to STR: ATXN10_ATTCT.
Early onset or syndromic epilepsy v0.1409 CSTB_CCCCGCCCCGCG Arianna Tucci Classified STR: CSTB_CCCCGCCCCGCG as Green List (high evidence)
Early onset or syndromic epilepsy v0.1409 CSTB_CCCCGCCCCGCG Arianna Tucci Str: cstb_ccccgccccgcg has been classified as Green List (High Evidence).
Hereditary neuropathy v1.37 ATXN10_ATTCT Louise Daugherty Tag STR tag was added to STR: ATXN10_ATTCT.
Early onset dystonia v1.58 ATXN10_ATTCT Louise Daugherty Tag STR tag was added to STR: ATXN10_ATTCT.
Early onset or syndromic epilepsy v0.1408 CSTB_CCCCGCCCCGCG Arianna Tucci STR: CSTB_CCCCGCCCCGCG was added
STR: CSTB_CCCCGCCCCGCG was added to Genetic epilepsy syndromes. Sources: Expert list
Mode of inheritance for STR: CSTB_CCCCGCCCCGCG was set to BIALLELIC, autosomal or pseudoautosomal
Added comment: Added to the panel following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Sources: Expert list
Early onset or syndromic epilepsy v0.1407 PSAP Eleanor Williams Classified gene: PSAP as Amber List (moderate evidence)
Early onset or syndromic epilepsy v0.1407 PSAP Eleanor Williams Added comment: Comment on list classification: Keeping Amber rating, as only 1 confirmed case of a variant in PSAP in a n individual with seizures. A mouse model which does develop seizures also exists.
Early onset or syndromic epilepsy v0.1407 PSAP Eleanor Williams Gene: psap has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1406 ATN1_CAG Arianna Tucci Marked STR: ATN1_CAG as ready
Early onset or syndromic epilepsy v0.1406 ATN1_CAG Arianna Tucci Added comment: Comment when marking as ready: Added to the panel following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Early onset or syndromic epilepsy v0.1406 ATN1_CAG Arianna Tucci Str: atn1_cag has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1406 PSAP Eleanor Williams commented on gene: PSAP: A mouse SAP -/- knockout exists (PMID: 8776585) and surviving mice develop intermittent seizures and progress to continual tonic status epilepticus.
Early onset or syndromic epilepsy v0.1406 ATN1_CAG Arianna Tucci Classified STR: ATN1_CAG as Green List (high evidence)
Early onset or syndromic epilepsy v0.1406 ATN1_CAG Arianna Tucci Str: atn1_cag has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1405 ATN1_CAG Arianna Tucci STR: ATN1_CAG was added
STR: ATN1_CAG was added to Genetic epilepsy syndromes. Sources: Expert Review
Mode of inheritance for STR: ATN1_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for STR: ATN1_CAG was set to GREEN
Added comment: Sources: Expert Review
Intellectual disability v2.566 ATXN1_CAG Louise Daugherty Pathogenic Number of Repeats for ATXN1_CAG was changed from 39 to 44.
Intellectual disability v2.565 ATXN1_CAG Louise Daugherty Classified STR: ATXN1_CAG as No list
Intellectual disability v2.565 ATXN1_CAG Louise Daugherty Added comment: Comment on list classification: Removed STR from Panel. This STR was not listed on the recent GMC STRs document supplied by Arianna Tucci
Intellectual disability v2.565 ATXN1_CAG Louise Daugherty Str: atxn1_cag has been removed from the panel.
Early onset or syndromic epilepsy v0.1404 PSAP Eleanor Williams commented on gene: PSAP: Metachromatic leukodystrophy due to SAP-b deficiency
2 cases of children with variants in PSAP and saposin B deficiency have been reported in PMID: 8554069 (Henseler et al. 1996) and PMID: 10682309 (Wrobe et al. 2000). Neither child was reported to have seizures.
Early onset or syndromic epilepsy v0.1404 PSAP Eleanor Williams commented on gene: PSAP: Combined SAP deficiency
PMIDs: 2514102 (Harzer et al. 1989) and 1371116 (Schnabel et al. 1992) report 2 sibs with combined SAP deficiency with a homozygous mutation resulting in a M1L substitution. No precursor and no mature SAPs were detected in the patient's cells. Both parents were heterozygous for the mutation. Can't access full text for PMID: 2514102 to assess phenotype.

PMID: 11309366 (Hulkova et al. 2001) - In a Slovakian patient with fatal infantile combined SAP deficiency, a homozygous for a 1 bp deletion in the PSAP gene, inherited from both his parents . Immunohistochemical investigations indicated that saposins A, B, C, and D were all deficient. Generalized seizures developed within minutes of birth.
Early onset or syndromic epilepsy v0.1404 PSAP Eleanor Williams commented on gene: PSAP
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.34 ATXN1_CAG Louise Daugherty Tag STR tag was added to STR: ATXN1_CAG.
Hereditary spastic paraplegia v1.95 ATXN1_CAG Louise Daugherty Tag STR tag was added to STR: ATXN1_CAG.
Parkinson Disease and Complex Parkinsonism v1.57 ATXN1_CAG Louise Daugherty Tag STR tag was added to STR: ATXN1_CAG.
Hereditary neuropathy v1.37 ATXN1_CAG Louise Daugherty Tag STR tag was added to STR: ATXN1_CAG.
Parkinson Disease and Complex Parkinsonism v1.57 ATN1_CAG Louise Daugherty Tag STR tag was added to STR: ATN1_CAG.
Distal myopathies v1.9 AR_CAG Louise Daugherty Tag STR tag was added to STR: AR_CAG.
Congenital myopathy v1.65 AR_CAG Louise Daugherty Tag STR tag was added to STR: AR_CAG.
Paediatric motor neuronopathies v1.18 AR_CAG Louise Daugherty Classified STR: AR_CAG as No list
Paediatric motor neuronopathies v1.18 AR_CAG Louise Daugherty Added comment: Comment on list classification: Removed STR from Panel. This STR was not listed on the recent GMC STRs document supplied by Arianna Tucci
Paediatric motor neuronopathies v1.18 AR_CAG Louise Daugherty Str: ar_cag has been removed from the panel.
Early onset or syndromic epilepsy v0.1404 PPP3CA Eleanor Williams Marked gene: PPP3CA as ready
Early onset or syndromic epilepsy v0.1404 PPP3CA Eleanor Williams Gene: ppp3ca has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1404 PPP3CA Eleanor Williams Publications for gene: PPP3CA were set to
Early onset or syndromic epilepsy v0.1403 PPP3CA Eleanor Williams Phenotypes for gene: PPP3CA were changed from to Epileptic encephalopathy, infantile or early childhood, 1 617711
Early onset or syndromic epilepsy v0.1402 PPP3CA Eleanor Williams Mode of inheritance for gene: PPP3CA was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v0.1401 PPP3CA Eleanor Williams Classified gene: PPP3CA as Green List (high evidence)
Early onset or syndromic epilepsy v0.1401 PPP3CA Eleanor Williams Added comment: Comment on list classification: > 3 cases of de novo variants in this gene associated with Epileptic encephalopathy. Note variants in the catalytic domain result in loss of function and are associated with this phenotype. Variants in the AI domain of the protein are not thought to be loss of function and the clinical phenotype does not always include seizures.
Early onset or syndromic epilepsy v0.1401 PPP3CA Eleanor Williams Gene: ppp3ca has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1400 PPP3CA Eleanor Williams commented on gene: PPP3CA
Intellectual disability v2.564 TRMT1 Konstantinos Varvagiannis reviewed gene: TRMT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30289604, 21937992, 26308914, 28784718; Phenotypes: Global developmental delay, Intellectual disability, Seizures, Microcephaly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.10 CDKN2C Ivone Leong reviewed gene: CDKN2C: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.10 CDKN2B Ivone Leong reviewed gene: CDKN2B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.10 CDKN1A Ivone Leong reviewed gene: CDKN1A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.10 CDKN1A Ivone Leong Publications for gene: CDKN1A were set to
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.9 CDKN2B Ivone Leong Publications for gene: CDKN2B were set to
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.8 CDKN2C Ivone Leong Publications for gene: CDKN2C were set to
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.7 CDKN2C Ivone Leong Phenotypes for gene: CDKN2C were changed from No OMIM number to No OMIM number; Multiple endocrine neoplasia 1
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.6 CDKN2B Ivone Leong Phenotypes for gene: CDKN2B were changed from No OMIM number to No OMIM number; Multiple endocrine neoplasia 1
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.5 CDKN1A Ivone Leong Phenotypes for gene: CDKN1A were changed from No OMIM number to No OMIM number; Multiple endocrine neoplasia 1
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.4 GCM2 Ivone Leong Classified gene: GCM2 as Green List (high evidence)
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.4 GCM2 Ivone Leong Added comment: Comment on list classification: Promoted from red to green based on below comment.
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.4 GCM2 Ivone Leong Gene: gcm2 has been classified as Green List (High Evidence).
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.3 GCM2 Ivone Leong Publications for gene: GCM2 were set to 27745835; 29264504
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.2 GCM2 Ivone Leong reviewed gene: GCM2: Rating: GREEN; Mode of pathogenicity: Other; Publications: ; Phenotypes: ; Mode of inheritance: None
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.2 RET Ivone Leong Added comment: Comment on mode of pathogenicity: Variants in RET cause gain-of-function effects.
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.2 RET Ivone Leong Mode of pathogenicity for gene: RET was changed from to Other
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.1 RET Ivone Leong commented on gene: RET
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.1 MEN1 Ivone Leong commented on gene: MEN1
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.1 CDKN1B Ivone Leong commented on gene: CDKN1B
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.1 CASR Ivone Leong commented on gene: CASR
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.1 CDC73 Ivone Leong commented on gene: CDC73
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.1 RET Ivone Leong gene: RET was added
gene: RET was added to Familial hyperparathyroidism. Sources: Emory Genetics Laboratory,UKGTN,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: RET was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: RET were set to Multiple endocrine neoplasia IIB (162300); Multiple endocrine neoplasia IIA (171400)
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.1 MEN1 Ivone Leong gene: MEN1 was added
gene: MEN1 was added to Familial hyperparathyroidism. Sources: Emory Genetics Laboratory,UKGTN,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: MEN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: MEN1 were set to Multiple endocrine neoplasia 1 (131100)
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.1 GCM2 Ivone Leong gene: GCM2 was added
gene: GCM2 was added to Familial hyperparathyroidism. Sources: Radboud University Medical Center, Nijmegen,Literature
Mode of inheritance for gene: GCM2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: GCM2 were set to 27745835; 29264504
Phenotypes for gene: GCM2 were set to Hypoparathyroidism, familial isolated (146200); Hyperparathyroidism 4 (617343)
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.1 CDKN2C Ivone Leong gene: CDKN2C was added
gene: CDKN2C was added to Familial hyperparathyroidism. Sources: UKGTN
Mode of inheritance for gene: CDKN2C was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: CDKN2C were set to No OMIM number
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.1 CDKN2B Ivone Leong gene: CDKN2B was added
gene: CDKN2B was added to Familial hyperparathyroidism. Sources: UKGTN
Mode of inheritance for gene: CDKN2B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: CDKN2B were set to No OMIM number
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.1 CDKN1B Ivone Leong gene: CDKN1B was added
gene: CDKN1B was added to Familial hyperparathyroidism. Sources: Emory Genetics Laboratory,UKGTN,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: CDKN1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: CDKN1B were set to Multiple endocrine neoplasia, type IV (610755)
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.1 CDKN1A Ivone Leong gene: CDKN1A was added
gene: CDKN1A was added to Familial hyperparathyroidism. Sources: UKGTN
Mode of inheritance for gene: CDKN1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: CDKN1A were set to No OMIM number
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.1 CDC73 Ivone Leong gene: CDC73 was added
gene: CDC73 was added to Familial hyperparathyroidism. Sources: Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,UKGTN,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: CDC73 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CDC73 were set to 12434154; 15531515
Phenotypes for gene: CDC73 were set to Hyperparathyroidism, familial primary (145000); Hyperparathyroidism-jaw tumor syndrome (145001)
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia v0.1 CASR Ivone Leong gene: CASR was added
gene: CASR was added to Familial hyperparathyroidism. Sources: Radboud University Medical Center, Nijmegen,UKGTN,Illumina TruGenome Clinical Sequencing Services
Mode of inheritance for gene: CASR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CASR were set to 15292296; 7916660; 9253359; 8675635
Phenotypes for gene: CASR were set to Hyperparathyroidism, neonatal (239200); Hypocalcemia, autosomal dominant (601198)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 ZMYND10 Louise Daugherty Source Expert Review Green was added to ZMYND10.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 TTC25 Louise Daugherty Source Expert Review Green was added to TTC25.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 TAPT1 Louise Daugherty Source Expert Review Amber was added to TAPT1.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 STK36 Louise Daugherty Source Expert Review Green was added to STK36.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 SPAG17 Louise Daugherty Source Expert Review Red was added to SPAG17.
Respiratory ciliopathies including non-CF bronchiectasis v0.3 SPAG1 Louise Daugherty Source Expert Review Green was added to SPAG1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 SCNN1G Louise Daugherty Source Expert Review Green was added to SCNN1G.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 SCNN1B Louise Daugherty Source Expert Review Green was added to SCNN1B.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 SCNN1A Louise Daugherty Source Expert Review Green was added to SCNN1A.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 RSPH9 Louise Daugherty Source Expert Review Green was added to RSPH9.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 RSPH4A Louise Daugherty Source Expert Review Green was added to RSPH4A.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 RSPH3 Louise Daugherty Source Expert Review Green was added to RSPH3.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 RSPH1 Louise Daugherty Source Expert Review Green was added to RSPH1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 RPGR Louise Daugherty Source Expert Review Amber was added to RPGR.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 PIK3CD Louise Daugherty Source Expert Review Amber was added to PIK3CD.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 PIH1D3 Louise Daugherty Source Expert Review Green was added to PIH1D3.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 ORMDL3 Louise Daugherty Source Expert Review Red was added to ORMDL3.
Respiratory ciliopathies including non-CF bronchiectasis v0.3 OFD1 Louise Daugherty Source Expert Review Amber was added to OFD1.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 NME8 Louise Daugherty Source Expert Review Green was added to NME8.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 MCIDAS Louise Daugherty Source Expert Review Green was added to MCIDAS.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 LRRC6 Louise Daugherty Source Expert Review Green was added to LRRC6.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 LRRC56 Louise Daugherty Source Expert Review Green was added to LRRC56.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 HYDIN Louise Daugherty Source Expert Review Green was added to HYDIN.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 GAS8 Louise Daugherty Source Expert Review Green was added to GAS8.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 DRC1 Louise Daugherty Source Expert Review Green was added to DRC1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 DNAL1 Louise Daugherty Source Expert Review Green was added to DNAL1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 DNAJB13 Louise Daugherty Source Expert Review Green was added to DNAJB13.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 DNAI2 Louise Daugherty Source Expert Review Green was added to DNAI2.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 DNAI1 Louise Daugherty Source Expert Review Green was added to DNAI1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 DNAH9 Louise Daugherty Source Expert Review Amber was added to DNAH9.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 DNAH8 Louise Daugherty Source Expert Review Green was added to DNAH8.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 DNAH6 Louise Daugherty Source Expert Review Amber was added to DNAH6.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 DNAH5 Louise Daugherty Source Expert Review Green was added to DNAH5.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 DNAH11 Louise Daugherty Source Expert Review Green was added to DNAH11.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 DNAH1 Louise Daugherty Source Expert Review Amber was added to DNAH1.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 DNAAF5 Louise Daugherty Source Expert Review Green was added to DNAAF5.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 DNAAF4 Louise Daugherty Source Expert Review Green was added to DNAAF4.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 DNAAF3 Louise Daugherty Source Expert Review Green was added to DNAAF3.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 DNAAF2 Louise Daugherty Source Expert Review Green was added to DNAAF2.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 DNAAF1 Louise Daugherty Source Expert Review Green was added to DNAAF1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 CFTR Louise Daugherty Source Expert Review Green was added to CFTR.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 CFAP54 Louise Daugherty Source Expert Review Amber was added to CFAP54.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 CFAP46 Louise Daugherty Source Expert Review Amber was added to CFAP46.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 CENPF Louise Daugherty Source Expert Review Green was added to CENPF.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 CCNO Louise Daugherty Source Expert Review Green was added to CCNO.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 CCDC65 Louise Daugherty Source Expert Review Green was added to CCDC65.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 CCDC40 Louise Daugherty Source Expert Review Green was added to CCDC40.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 CCDC39 Louise Daugherty Source Expert Review Green was added to CCDC39.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 CCDC151 Louise Daugherty Source Expert Review Green was added to CCDC151.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 CCDC114 Louise Daugherty Source Expert Review Green was added to CCDC114.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 CCDC103 Louise Daugherty Source Expert Review Green was added to CCDC103.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 C21orf59 Louise Daugherty Source Expert Review Green was added to C21orf59.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 C11orf70 Louise Daugherty Source Expert Review Green was added to C11orf70.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 ARMC4 Louise Daugherty Source Expert Review Green was added to ARMC4.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v0.3 AGPAT2 Louise Daugherty Source Expert Review Red was added to AGPAT2.
Respiratory ciliopathies including non-CF bronchiectasis v0.2 ZMYND10 Louise Daugherty reviewed gene: ZMYND10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 TTC25 Louise Daugherty reviewed gene: TTC25: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 TAPT1 Louise Daugherty reviewed gene: TAPT1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 STK36 Louise Daugherty reviewed gene: STK36: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 SPAG17 Louise Daugherty reviewed gene: SPAG17: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 SPAG1 Louise Daugherty reviewed gene: SPAG1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 SCNN1G Louise Daugherty reviewed gene: SCNN1G: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 SCNN1B Louise Daugherty reviewed gene: SCNN1B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 SCNN1A Louise Daugherty reviewed gene: SCNN1A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 RSPH9 Louise Daugherty reviewed gene: RSPH9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 RSPH4A Louise Daugherty reviewed gene: RSPH4A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 RSPH3 Louise Daugherty reviewed gene: RSPH3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 RSPH1 Louise Daugherty reviewed gene: RSPH1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 RPGR Louise Daugherty reviewed gene: RPGR: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 PIK3CD Louise Daugherty reviewed gene: PIK3CD: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 PIH1D3 Louise Daugherty reviewed gene: PIH1D3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 ORMDL3 Louise Daugherty reviewed gene: ORMDL3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 OFD1 Louise Daugherty reviewed gene: OFD1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 NME8 Louise Daugherty reviewed gene: NME8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 MCIDAS Louise Daugherty reviewed gene: MCIDAS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 LRRC6 Louise Daugherty reviewed gene: LRRC6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 LRRC56 Louise Daugherty reviewed gene: LRRC56: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 HYDIN Louise Daugherty reviewed gene: HYDIN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 GAS8 Louise Daugherty reviewed gene: GAS8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 DRC1 Louise Daugherty reviewed gene: DRC1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 DNAL1 Louise Daugherty reviewed gene: DNAL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 DNAJB13 Louise Daugherty reviewed gene: DNAJB13: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 DNAI2 Louise Daugherty reviewed gene: DNAI2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 DNAI1 Louise Daugherty reviewed gene: DNAI1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 DNAH9 Louise Daugherty reviewed gene: DNAH9: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 DNAH8 Louise Daugherty reviewed gene: DNAH8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 DNAH6 Louise Daugherty reviewed gene: DNAH6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 DNAH5 Louise Daugherty reviewed gene: DNAH5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 DNAH11 Louise Daugherty reviewed gene: DNAH11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 DNAH1 Louise Daugherty reviewed gene: DNAH1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 DNAAF5 Louise Daugherty reviewed gene: DNAAF5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 DNAAF4 Louise Daugherty reviewed gene: DNAAF4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 DNAAF3 Louise Daugherty reviewed gene: DNAAF3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 DNAAF2 Louise Daugherty reviewed gene: DNAAF2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 DNAAF1 Louise Daugherty reviewed gene: DNAAF1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 CFTR Louise Daugherty reviewed gene: CFTR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 CFAP54 Louise Daugherty reviewed gene: CFAP54: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 CFAP46 Louise Daugherty reviewed gene: CFAP46: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 CENPF Louise Daugherty reviewed gene: CENPF: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 CCNO Louise Daugherty reviewed gene: CCNO: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 CCDC65 Louise Daugherty reviewed gene: CCDC65: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 CCDC40 Louise Daugherty reviewed gene: CCDC40: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 CCDC39 Louise Daugherty reviewed gene: CCDC39: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 CCDC151 Louise Daugherty reviewed gene: CCDC151: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 CCDC114 Louise Daugherty reviewed gene: CCDC114: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 CCDC103 Louise Daugherty reviewed gene: CCDC103: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 C21orf59 Louise Daugherty reviewed gene: C21orf59: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 C11orf70 Louise Daugherty reviewed gene: C11orf70: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 ARMC4 Louise Daugherty reviewed gene: ARMC4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.2 AGPAT2 Louise Daugherty reviewed gene: AGPAT2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Respiratory ciliopathies including non-CF bronchiectasis v0.1 ZMYND10 Louise Daugherty gene: ZMYND10 was added
gene: ZMYND10 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: ZMYND10 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 TTC25 Louise Daugherty gene: TTC25 was added
gene: TTC25 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: TTC25 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 TAPT1 Louise Daugherty gene: TAPT1 was added
gene: TAPT1 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: TAPT1 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 STK36 Louise Daugherty gene: STK36 was added
gene: STK36 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: STK36 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 SPAG17 Louise Daugherty gene: SPAG17 was added
gene: SPAG17 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: SPAG17 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 SPAG1 Louise Daugherty gene: SPAG1 was added
gene: SPAG1 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: SPAG1 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 SCNN1G Louise Daugherty gene: SCNN1G was added
gene: SCNN1G was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: SCNN1G was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 SCNN1B Louise Daugherty gene: SCNN1B was added
gene: SCNN1B was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: SCNN1B was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 SCNN1A Louise Daugherty gene: SCNN1A was added
gene: SCNN1A was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: SCNN1A was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 RSPH9 Louise Daugherty gene: RSPH9 was added
gene: RSPH9 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: RSPH9 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 RSPH4A Louise Daugherty gene: RSPH4A was added
gene: RSPH4A was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: RSPH4A was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 RSPH3 Louise Daugherty gene: RSPH3 was added
gene: RSPH3 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: RSPH3 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 RSPH1 Louise Daugherty gene: RSPH1 was added
gene: RSPH1 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: RSPH1 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 RPGR Louise Daugherty gene: RPGR was added
gene: RPGR was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: RPGR was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 PIK3CD Louise Daugherty gene: PIK3CD was added
gene: PIK3CD was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: PIK3CD was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 PIH1D3 Louise Daugherty gene: PIH1D3 was added
gene: PIH1D3 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: PIH1D3 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 ORMDL3 Louise Daugherty gene: ORMDL3 was added
gene: ORMDL3 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: ORMDL3 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 OFD1 Louise Daugherty gene: OFD1 was added
gene: OFD1 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: OFD1 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 NME8 Louise Daugherty gene: NME8 was added
gene: NME8 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: NME8 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 MCIDAS Louise Daugherty gene: MCIDAS was added
gene: MCIDAS was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: MCIDAS was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 LRRC6 Louise Daugherty gene: LRRC6 was added
gene: LRRC6 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: LRRC6 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 LRRC56 Louise Daugherty gene: LRRC56 was added
gene: LRRC56 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: LRRC56 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 HYDIN Louise Daugherty gene: HYDIN was added
gene: HYDIN was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: HYDIN was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 GAS8 Louise Daugherty gene: GAS8 was added
gene: GAS8 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: GAS8 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 DRC1 Louise Daugherty gene: DRC1 was added
gene: DRC1 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: DRC1 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 DNAL1 Louise Daugherty gene: DNAL1 was added
gene: DNAL1 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: DNAL1 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 DNAJB13 Louise Daugherty gene: DNAJB13 was added
gene: DNAJB13 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: DNAJB13 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 DNAI2 Louise Daugherty gene: DNAI2 was added
gene: DNAI2 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: DNAI2 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 DNAI1 Louise Daugherty gene: DNAI1 was added
gene: DNAI1 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: DNAI1 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 DNAH9 Louise Daugherty gene: DNAH9 was added
gene: DNAH9 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: DNAH9 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 DNAH8 Louise Daugherty gene: DNAH8 was added
gene: DNAH8 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: DNAH8 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 DNAH6 Louise Daugherty gene: DNAH6 was added
gene: DNAH6 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: DNAH6 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 DNAH5 Louise Daugherty gene: DNAH5 was added
gene: DNAH5 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: DNAH5 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 DNAH11 Louise Daugherty gene: DNAH11 was added
gene: DNAH11 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: DNAH11 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 DNAH1 Louise Daugherty gene: DNAH1 was added
gene: DNAH1 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: DNAH1 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 DNAAF5 Louise Daugherty gene: DNAAF5 was added
gene: DNAAF5 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: DNAAF5 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 DNAAF4 Louise Daugherty gene: DNAAF4 was added
gene: DNAAF4 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: DNAAF4 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 DNAAF3 Louise Daugherty gene: DNAAF3 was added
gene: DNAAF3 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: DNAAF3 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 DNAAF2 Louise Daugherty gene: DNAAF2 was added
gene: DNAAF2 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: DNAAF2 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 DNAAF1 Louise Daugherty gene: DNAAF1 was added
gene: DNAAF1 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: DNAAF1 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 CFTR Louise Daugherty gene: CFTR was added
gene: CFTR was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: CFTR was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 CFAP54 Louise Daugherty gene: CFAP54 was added
gene: CFAP54 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: CFAP54 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 CFAP46 Louise Daugherty gene: CFAP46 was added
gene: CFAP46 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: CFAP46 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 CENPF Louise Daugherty gene: CENPF was added
gene: CENPF was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: CENPF was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 CCNO Louise Daugherty gene: CCNO was added
gene: CCNO was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: CCNO was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 CCDC65 Louise Daugherty gene: CCDC65 was added
gene: CCDC65 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: CCDC65 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 CCDC40 Louise Daugherty gene: CCDC40 was added
gene: CCDC40 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: CCDC40 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 CCDC39 Louise Daugherty gene: CCDC39 was added
gene: CCDC39 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: CCDC39 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 CCDC151 Louise Daugherty gene: CCDC151 was added
gene: CCDC151 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: CCDC151 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 CCDC114 Louise Daugherty gene: CCDC114 was added
gene: CCDC114 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: CCDC114 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 CCDC103 Louise Daugherty gene: CCDC103 was added
gene: CCDC103 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: CCDC103 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 C21orf59 Louise Daugherty gene: C21orf59 was added
gene: C21orf59 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: C21orf59 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 C11orf70 Louise Daugherty gene: C11orf70 was added
gene: C11orf70 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: C11orf70 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 ARMC4 Louise Daugherty gene: ARMC4 was added
gene: ARMC4 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: ARMC4 was set to
Respiratory ciliopathies including non-CF bronchiectasis v0.1 AGPAT2 Louise Daugherty gene: AGPAT2 was added
gene: AGPAT2 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: NHS GMS
Mode of inheritance for gene: AGPAT2 was set to
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.34 NOP56_GGCCTG Arianna Tucci Marked STR: NOP56_GGCCTG as ready
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.34 NOP56_GGCCTG Arianna Tucci Str: nop56_ggcctg has been classified as Green List (High Evidence).
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.34 NOP56_GGCCTG Arianna Tucci Classified STR: NOP56_GGCCTG as Green List (high evidence)
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.34 NOP56_GGCCTG Arianna Tucci Str: nop56_ggcctg has been classified as Green List (High Evidence).
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.33 NOP56_GGCCTG Arianna Tucci STR: NOP56_GGCCTG was added
STR: NOP56_GGCCTG was added to Early onset dementia (encompassing fronto-temporal dementia and prion disease). Sources: Expert Review
Mode of inheritance for STR: NOP56_GGCCTG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for STR: NOP56_GGCCTG was set to GREEN
Added comment: added to the panel following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Sources: Expert Review
Amyotrophic lateral sclerosis/motor neuron disease v1.22 NOP56_GGCCTG Arianna Tucci Classified STR: NOP56_GGCCTG as Green List (high evidence)
Amyotrophic lateral sclerosis/motor neuron disease v1.22 NOP56_GGCCTG Arianna Tucci Str: nop56_ggcctg has been classified as Green List (High Evidence).
Amyotrophic lateral sclerosis/motor neuron disease v1.21 NOP56_GGCCTG Arianna Tucci Marked STR: NOP56_GGCCTG as ready
Amyotrophic lateral sclerosis/motor neuron disease v1.21 NOP56_GGCCTG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Amyotrophic lateral sclerosis/motor neuron disease v1.21 NOP56_GGCCTG Arianna Tucci Str: nop56_ggcctg has been classified as Red List (Low Evidence).
Amyotrophic lateral sclerosis/motor neuron disease v1.21 NOP56_GGCCTG Arianna Tucci STR: NOP56_GGCCTG was added
STR: NOP56_GGCCTG was added to Amyotrophic lateral sclerosis/motor neuron disease. Sources: Expert Review
Mode of inheritance for STR: NOP56_GGCCTG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary ataxia v1.143 NOP56_GGCCTG Arianna Tucci Classified STR: NOP56_GGCCTG as Green List (high evidence)
Hereditary ataxia v1.143 NOP56_GGCCTG Arianna Tucci Str: nop56_ggcctg has been classified as Green List (High Evidence).
Hereditary ataxia v1.142 NOP56_GGCCTG Arianna Tucci Normal Number of Repeats for NOP56_GGCCTG was changed from 14 to 15.
Hereditary ataxia v1.141 NOP56_GGCCTG Arianna Tucci Marked STR: NOP56_GGCCTG as ready
Hereditary ataxia v1.141 NOP56_GGCCTG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Hereditary ataxia v1.141 NOP56_GGCCTG Arianna Tucci Str: nop56_ggcctg has been classified as Red List (Low Evidence).
Hereditary spastic paraplegia v1.95 TBP_CAG Arianna Tucci Marked STR: TBP_CAG as ready
Hereditary spastic paraplegia v1.95 TBP_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Hereditary spastic paraplegia v1.95 TBP_CAG Arianna Tucci Str: tbp_cag has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.95 TBP_CAG Arianna Tucci Classified STR: TBP_CAG as Green List (high evidence)
Hereditary spastic paraplegia v1.95 TBP_CAG Arianna Tucci Str: tbp_cag has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.94 TBP_CAG Arianna Tucci STR: TBP_CAG was added
STR: TBP_CAG was added to Hereditary spastic paraplegia. Sources: Expert Review
Mode of inheritance for STR: TBP_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
STR: TBP_CAG was marked as current diagnostic
Parkinson Disease and Complex Parkinsonism v1.57 PPP2R2B_CAG Arianna Tucci Marked STR: PPP2R2B_CAG as ready
Parkinson Disease and Complex Parkinsonism v1.57 PPP2R2B_CAG Arianna Tucci Str: ppp2r2b_cag has been classified as Green List (High Evidence).
Parkinson Disease and Complex Parkinsonism v1.57 PPP2R2B_CAG Arianna Tucci Classified STR: PPP2R2B_CAG as Green List (high evidence)
Parkinson Disease and Complex Parkinsonism v1.57 PPP2R2B_CAG Arianna Tucci Str: ppp2r2b_cag has been classified as Green List (High Evidence).
Parkinson Disease and Complex Parkinsonism v1.56 PPP2R2B_CAG Arianna Tucci commented on STR: PPP2R2B_CAG: Added to the panel following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Parkinson Disease and Complex Parkinsonism v1.56 PPP2R2B_CAG Arianna Tucci STR: PPP2R2B_CAG was added
STR: PPP2R2B_CAG was added to Parkinson Disease and Complex Parkinsonism. Sources: Expert Review
Mode of inheritance for STR: PPP2R2B_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for STR: PPP2R2B_CAG was set to GREEN
Added comment: Sources: Expert Review
Hereditary spastic paraplegia v1.93 PPP2R2B_CAG Arianna Tucci Classified STR: PPP2R2B_CAG as Green List (high evidence)
Hereditary spastic paraplegia v1.93 PPP2R2B_CAG Arianna Tucci Str: ppp2r2b_cag has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.92 PPP2R2B_CAG Arianna Tucci Marked STR: PPP2R2B_CAG as ready
Hereditary spastic paraplegia v1.92 PPP2R2B_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Hereditary spastic paraplegia v1.92 PPP2R2B_CAG Arianna Tucci Str: ppp2r2b_cag has been classified as Red List (Low Evidence).
Hereditary spastic paraplegia v1.92 PPP2R2B_CAG Arianna Tucci STR: PPP2R2B_CAG was added
STR: PPP2R2B_CAG was added to Hereditary spastic paraplegia. Sources: Expert Review
Mode of inheritance for STR: PPP2R2B_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
STR: PPP2R2B_CAG was marked as current diagnostic
Laterality disorders and isomerism v0.3 ZMYND10 Louise Daugherty Source Expert Review Green was added to ZMYND10.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 ZIC3 Louise Daugherty Source Expert Review Green was added to ZIC3.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 TTC25 Louise Daugherty Source Expert Review Green was added to TTC25.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 SPAG1 Louise Daugherty Source Expert Review Green was added to SPAG1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 RSPH9 Louise Daugherty Source Expert Review Green was added to RSPH9.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 RSPH4A Louise Daugherty Source Expert Review Green was added to RSPH4A.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 RSPH3 Louise Daugherty Source Expert Review Green was added to RSPH3.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 RSPH1 Louise Daugherty Source Expert Review Green was added to RSPH1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 PKD1L1 Louise Daugherty Source Expert Review Green was added to PKD1L1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 PIH1D3 Louise Daugherty Source Expert Review Green was added to PIH1D3.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 NSD2 Louise Daugherty Source Expert Review Red was added to NSD2.
Laterality disorders and isomerism v0.3 NPHP4 Louise Daugherty Source Expert Review Amber was added to NPHP4.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Laterality disorders and isomerism v0.3 NODAL Louise Daugherty Source Expert Review Green was added to NODAL.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 NME8 Louise Daugherty Source Expert Review Green was added to NME8.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 NKX2-5 Louise Daugherty Source Expert Review Amber was added to NKX2-5.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Laterality disorders and isomerism v0.3 MYH6 Louise Daugherty Source Expert Review Amber was added to MYH6.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Laterality disorders and isomerism v0.3 MMP21 Louise Daugherty Source Expert Review Green was added to MMP21.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 LZTFL1 Louise Daugherty Source Expert Review Amber was added to LZTFL1.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Laterality disorders and isomerism v0.3 LRRC6 Louise Daugherty Source Expert Review Green was added to LRRC6.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 LRRC56 Louise Daugherty Source Expert Review Green was added to LRRC56.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 LETM1 Louise Daugherty Source Expert Review Red was added to LETM1.
Laterality disorders and isomerism v0.3 HYDIN Louise Daugherty Source Expert Review Green was added to HYDIN.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 GDF1 Louise Daugherty Source Expert Review Green was added to GDF1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 GAS8 Louise Daugherty Source Expert Review Green was added to GAS8.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 FANCB Louise Daugherty Source Expert Review Amber was added to FANCB.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Laterality disorders and isomerism v0.3 DRC1 Louise Daugherty Source Expert Review Green was added to DRC1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 DNAL1 Louise Daugherty Source Expert Review Green was added to DNAL1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 DNAJB13 Louise Daugherty Source Expert Review Green was added to DNAJB13.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 DNAI2 Louise Daugherty Source Expert Review Green was added to DNAI2.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 DNAI1 Louise Daugherty Source Expert Review Green was added to DNAI1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 DNAH8 Louise Daugherty Source Expert Review Amber was added to DNAH8.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Laterality disorders and isomerism v0.3 DNAH5 Louise Daugherty Source Expert Review Green was added to DNAH5.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 DNAH11 Louise Daugherty Source Expert Review Green was added to DNAH11.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 DNAH1 Louise Daugherty Source Expert Review Green was added to DNAH1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 DNAAF5 Louise Daugherty Source Expert Review Green was added to DNAAF5.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 DNAAF4 Louise Daugherty Source Expert Review Green was added to DNAAF4.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 DNAAF3 Louise Daugherty Source Expert Review Green was added to DNAAF3.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 DNAAF2 Louise Daugherty Source Expert Review Green was added to DNAAF2.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 DNAAF1 Louise Daugherty Source Expert Review Green was added to DNAAF1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 CRELD1 Louise Daugherty Source Expert Review Green was added to CRELD1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 CFC1 Louise Daugherty Source Expert Review Green was added to CFC1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 CFAP53 Louise Daugherty Source Expert Review Green was added to CFAP53.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 C11orf70 Louise Daugherty Source Expert Review Green was added to C11orf70.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 CCNO Louise Daugherty Source Expert Review Green was added to CCNO.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 CCDC65 Louise Daugherty Source Expert Review Green was added to CCDC65.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 CCDC40 Louise Daugherty Source Expert Review Green was added to CCDC40.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 CCDC39 Louise Daugherty Source Expert Review Green was added to CCDC39.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 CCDC151 Louise Daugherty Source Expert Review Green was added to CCDC151.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 CCDC114 Louise Daugherty Source Expert Review Green was added to CCDC114.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 CCDC103 Louise Daugherty Source Expert Review Green was added to CCDC103.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 C21orf59 Louise Daugherty Source Expert Review Green was added to C21orf59.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 ARMC4 Louise Daugherty Source Expert Review Green was added to ARMC4.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 ACVR2B Louise Daugherty Source Expert Review Green was added to ACVR2B.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Laterality disorders and isomerism v0.3 ACTG2 Louise Daugherty Source Expert Review Amber was added to ACTG2.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Laterality disorders and isomerism v0.3 ACTC1 Louise Daugherty Source Expert Review Amber was added to ACTC1.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Brain channelopathy v1.40 TBP_CAG Arianna Tucci Classified STR: TBP_CAG as Green List (high evidence)
Brain channelopathy v1.40 TBP_CAG Arianna Tucci Str: tbp_cag has been classified as Green List (High Evidence).
Brain channelopathy v1.39 TBP_CAG Arianna Tucci Marked STR: TBP_CAG as ready
Brain channelopathy v1.39 TBP_CAG Arianna Tucci Added comment: Comment when marking as ready: Added to the panel following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Brain channelopathy v1.39 TBP_CAG Arianna Tucci Str: tbp_cag has been classified as Red List (Low Evidence).
Brain channelopathy v1.39 TBP_CAG Arianna Tucci STR: TBP_CAG was added
STR: TBP_CAG was added to Brain channelopathy. Sources: Expert Review
Mode of inheritance for STR: TBP_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
STR: TBP_CAG was marked as current diagnostic
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.32 TBP_CAG Arianna Tucci Marked STR: TBP_CAG as ready
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.32 TBP_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.32 TBP_CAG Arianna Tucci Str: tbp_cag has been classified as Green List (High Evidence).
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.32 TBP_CAG Arianna Tucci Classified STR: TBP_CAG as Green List (high evidence)
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.32 TBP_CAG Arianna Tucci Str: tbp_cag has been classified as Green List (High Evidence).
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.31 TBP_CAG Arianna Tucci STR: TBP_CAG was added
STR: TBP_CAG was added to Early onset dementia (encompassing fronto-temporal dementia and prion disease). Sources: Expert Review
Mode of inheritance for STR: TBP_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
STR: TBP_CAG was marked as current diagnostic
Parkinson Disease and Complex Parkinsonism v1.55 TBP_CAG Arianna Tucci Marked STR: TBP_CAG as ready
Parkinson Disease and Complex Parkinsonism v1.55 TBP_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Parkinson Disease and Complex Parkinsonism v1.55 TBP_CAG Arianna Tucci Str: tbp_cag has been classified as Green List (High Evidence).
Parkinson Disease and Complex Parkinsonism v1.55 TBP_CAG Arianna Tucci Classified STR: TBP_CAG as Green List (high evidence)
Parkinson Disease and Complex Parkinsonism v1.55 TBP_CAG Arianna Tucci Str: tbp_cag has been classified as Green List (High Evidence).
Parkinson Disease and Complex Parkinsonism v1.54 TBP_CAG Arianna Tucci Normal Number of Repeats for TBP_CAG was changed from 40 to 41.
Hereditary ataxia v1.141 TBP_CAG Arianna Tucci Marked STR: TBP_CAG as ready
Hereditary ataxia v1.141 TBP_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Hereditary ataxia v1.141 TBP_CAG Arianna Tucci Str: tbp_cag has been classified as Green List (High Evidence).
Hereditary ataxia v1.141 TBP_CAG Arianna Tucci Classified STR: TBP_CAG as Green List (high evidence)
Hereditary ataxia v1.141 TBP_CAG Arianna Tucci Str: tbp_cag has been classified as Green List (High Evidence).
Hereditary ataxia v1.140 TBP_CAG Arianna Tucci Normal Number of Repeats for TBP_CAG was changed from 40 to 41.
Early onset or syndromic epilepsy v0.1400 POMT1 Eleanor Williams Marked gene: POMT1 as ready
Early onset or syndromic epilepsy v0.1400 POMT1 Eleanor Williams Gene: pomt1 has been classified as Green List (High Evidence).
Hereditary neuropathy v1.37 ATXN10_ATTCT Arianna Tucci Marked STR: ATXN10_ATTCT as ready
Hereditary neuropathy v1.37 ATXN10_ATTCT Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Hereditary neuropathy v1.37 ATXN10_ATTCT Arianna Tucci Str: atxn10_attct has been classified as Green List (High Evidence).
Hereditary neuropathy v1.37 ATXN10_ATTCT Arianna Tucci Classified STR: ATXN10_ATTCT as Green List (high evidence)
Hereditary neuropathy v1.37 ATXN10_ATTCT Arianna Tucci Str: atxn10_attct has been classified as Green List (High Evidence).
Hereditary neuropathy v1.36 ATXN10_ATTCT Arianna Tucci STR: ATXN10_ATTCT was added
STR: ATXN10_ATTCT was added to Hereditary neuropathy. Sources: Expert Review
Mode of inheritance for STR: ATXN10_ATTCT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added comment: Added to the panel following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Sources: Expert Review
Early onset or syndromic epilepsy v0.1400 POMT1 Eleanor Williams Phenotypes for gene: POMT1 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 236670
Early onset or syndromic epilepsy v0.1399 POMT1 Eleanor Williams Publications for gene: POMT1 were set to
Early onset dystonia v1.58 ATXN10_ATTCT Arianna Tucci Marked STR: ATXN10_ATTCT as ready
Early onset dystonia v1.58 ATXN10_ATTCT Arianna Tucci Str: atxn10_attct has been classified as Red List (Low Evidence).
Early onset dystonia v1.58 ATXN10_ATTCT Arianna Tucci Classified STR: ATXN10_ATTCT as Red List (low evidence)
Early onset dystonia v1.58 ATXN10_ATTCT Arianna Tucci Str: atxn10_attct has been classified as Red List (Low Evidence).
Early onset dystonia v1.57 ATXN10_ATTCT Arianna Tucci Marked STR: ATXN10_ATTCT as ready
Early onset dystonia v1.57 ATXN10_ATTCT Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Early onset dystonia v1.57 ATXN10_ATTCT Arianna Tucci Str: atxn10_attct has been classified as Green List (High Evidence).
Early onset dystonia v1.57 ATXN10_ATTCT Arianna Tucci Classified STR: ATXN10_ATTCT as Green List (high evidence)
Early onset dystonia v1.57 ATXN10_ATTCT Arianna Tucci Str: atxn10_attct has been classified as Green List (High Evidence).
Early onset dystonia v1.56 ATXN10_ATTCT Arianna Tucci STR: ATXN10_ATTCT was added
STR: ATXN10_ATTCT was added to Early onset dystonia. Sources: Expert Review
Mode of inheritance for STR: ATXN10_ATTCT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added comment: Added to the panel following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Sources: Expert Review
Early onset or syndromic epilepsy v0.1398 POMT1 Eleanor Williams Mode of inheritance for gene: POMT1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1397 POMT1 Eleanor Williams Classified gene: POMT1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1397 POMT1 Eleanor Williams Added comment: Comment on list classification: >3 cases of variants in this gene in patients with a relevant phenotype. £ patients reported with seizures.
Early onset or syndromic epilepsy v0.1397 POMT1 Eleanor Williams Gene: pomt1 has been classified as Green List (High Evidence).
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.30 ATXN10_ATTCT Arianna Tucci Marked STR: ATXN10_ATTCT as ready
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.30 ATXN10_ATTCT Arianna Tucci Added comment: Comment when marking as ready: Added to the panel following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.30 ATXN10_ATTCT Arianna Tucci Str: atxn10_attct has been classified as Green List (High Evidence).
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.30 ATXN10_ATTCT Arianna Tucci Classified STR: ATXN10_ATTCT as Green List (high evidence)
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.30 ATXN10_ATTCT Arianna Tucci Str: atxn10_attct has been classified as Green List (High Evidence).
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.29 ATXN10_ATTCT Arianna Tucci STR: ATXN10_ATTCT was added
STR: ATXN10_ATTCT was added to Early onset dementia (encompassing fronto-temporal dementia and prion disease). Sources: Expert Review
Mode of inheritance for STR: ATXN10_ATTCT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added comment: Added to the panel following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Sources: Expert Review
Early onset or syndromic epilepsy v0.1396 POMT1 Eleanor Williams commented on gene: POMT1
Hereditary spastic paraplegia v1.91 ATXN10_ATTCT Arianna Tucci Marked STR: ATXN10_ATTCT as ready
Hereditary spastic paraplegia v1.91 ATXN10_ATTCT Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Hereditary spastic paraplegia v1.91 ATXN10_ATTCT Arianna Tucci Str: atxn10_attct has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.91 ATXN10_ATTCT Arianna Tucci Classified STR: ATXN10_ATTCT as Green List (high evidence)
Hereditary spastic paraplegia v1.91 ATXN10_ATTCT Arianna Tucci Str: atxn10_attct has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.90 ATXN10_ATTCT Arianna Tucci STR: ATXN10_ATTCT was added
STR: ATXN10_ATTCT was added to Hereditary spastic paraplegia. Sources: Expert Review
Mode of inheritance for STR: ATXN10_ATTCT was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
STR: ATXN10_ATTCT was marked as current diagnostic
Hereditary ataxia v1.139 ATXN10_ATTCT Arianna Tucci Marked STR: ATXN10_ATTCT as ready
Hereditary ataxia v1.139 ATXN10_ATTCT Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Hereditary ataxia v1.139 ATXN10_ATTCT Arianna Tucci Str: atxn10_attct has been classified as Green List (High Evidence).
Hereditary ataxia v1.139 ATXN10_ATTCT Arianna Tucci Classified STR: ATXN10_ATTCT as Green List (high evidence)
Hereditary ataxia v1.139 ATXN10_ATTCT Arianna Tucci Str: atxn10_attct has been classified as Green List (High Evidence).
Hereditary ataxia v1.138 ATXN7_CAG Arianna Tucci Classified STR: ATXN7_CAG as Green List (high evidence)
Hereditary ataxia v1.138 ATXN7_CAG Arianna Tucci Str: atxn7_cag has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.89 ATXN7_CAG Arianna Tucci Marked STR: ATXN7_CAG as ready
Hereditary spastic paraplegia v1.89 ATXN7_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Hereditary spastic paraplegia v1.89 ATXN7_CAG Arianna Tucci Str: atxn7_cag has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.89 ATXN7_CAG Arianna Tucci Classified STR: ATXN7_CAG as Green List (high evidence)
Hereditary spastic paraplegia v1.89 ATXN7_CAG Arianna Tucci Str: atxn7_cag has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.88 ATXN7_CAG Arianna Tucci STR: ATXN7_CAG was added
STR: ATXN7_CAG was added to Hereditary spastic paraplegia. Sources: Expert Review
Mode of inheritance for STR: ATXN7_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
STR: ATXN7_CAG was marked as current diagnostic
Hereditary ataxia v1.137 ATXN7_CAG Arianna Tucci Marked STR: ATXN7_CAG as ready
Hereditary ataxia v1.137 ATXN7_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Hereditary ataxia v1.137 ATXN7_CAG Arianna Tucci Str: atxn7_cag has been classified as Red List (Low Evidence).
Laterality disorders and isomerism v0.2 ZMYND10 Louise Daugherty reviewed gene: ZMYND10: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 ZIC3 Louise Daugherty reviewed gene: ZIC3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 TTC25 Louise Daugherty reviewed gene: TTC25: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 SPAG1 Louise Daugherty reviewed gene: SPAG1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 RSPH9 Louise Daugherty reviewed gene: RSPH9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 RSPH4A Louise Daugherty reviewed gene: RSPH4A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 RSPH3 Louise Daugherty reviewed gene: RSPH3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 RSPH1 Louise Daugherty reviewed gene: RSPH1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 PKD1L1 Louise Daugherty reviewed gene: PKD1L1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 PIH1D3 Louise Daugherty reviewed gene: PIH1D3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 NSD2 Louise Daugherty reviewed gene: NSD2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 NPHP4 Louise Daugherty reviewed gene: NPHP4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 NODAL Louise Daugherty reviewed gene: NODAL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 NME8 Louise Daugherty reviewed gene: NME8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 NKX2-5 Louise Daugherty reviewed gene: NKX2-5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 MYH6 Louise Daugherty reviewed gene: MYH6: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 MMP21 Louise Daugherty reviewed gene: MMP21: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 LZTFL1 Louise Daugherty reviewed gene: LZTFL1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 LRRC6 Louise Daugherty reviewed gene: LRRC6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 LRRC56 Louise Daugherty reviewed gene: LRRC56: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 LETM1 Louise Daugherty reviewed gene: LETM1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 HYDIN Louise Daugherty reviewed gene: HYDIN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 GDF1 Louise Daugherty reviewed gene: GDF1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 GAS8 Louise Daugherty reviewed gene: GAS8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 FANCB Louise Daugherty reviewed gene: FANCB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 DRC1 Louise Daugherty reviewed gene: DRC1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 DNAL1 Louise Daugherty reviewed gene: DNAL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 DNAJB13 Louise Daugherty reviewed gene: DNAJB13: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 DNAI2 Louise Daugherty reviewed gene: DNAI2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 DNAI1 Louise Daugherty reviewed gene: DNAI1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 DNAH8 Louise Daugherty reviewed gene: DNAH8: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 DNAH5 Louise Daugherty reviewed gene: DNAH5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 DNAH11 Louise Daugherty reviewed gene: DNAH11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 DNAH1 Louise Daugherty reviewed gene: DNAH1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 DNAAF5 Louise Daugherty reviewed gene: DNAAF5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 DNAAF4 Louise Daugherty reviewed gene: DNAAF4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 DNAAF3 Louise Daugherty reviewed gene: DNAAF3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 DNAAF2 Louise Daugherty reviewed gene: DNAAF2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 DNAAF1 Louise Daugherty reviewed gene: DNAAF1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 CRELD1 Louise Daugherty reviewed gene: CRELD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 CFC1 Louise Daugherty reviewed gene: CFC1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 CFAP53 Louise Daugherty reviewed gene: CFAP53: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 CCNO Louise Daugherty reviewed gene: CCNO: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 CCDC65 Louise Daugherty reviewed gene: CCDC65: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 CCDC40 Louise Daugherty reviewed gene: CCDC40: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 CCDC39 Louise Daugherty reviewed gene: CCDC39: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 CCDC151 Louise Daugherty reviewed gene: CCDC151: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 CCDC114 Louise Daugherty reviewed gene: CCDC114: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 CCDC103 Louise Daugherty reviewed gene: CCDC103: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 C21orf59 Louise Daugherty reviewed gene: C21orf59: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 C11orf70 Louise Daugherty reviewed gene: C11orf70: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 ARMC4 Louise Daugherty reviewed gene: ARMC4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 ACVR2B Louise Daugherty reviewed gene: ACVR2B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 ACTG2 Louise Daugherty reviewed gene: ACTG2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Laterality disorders and isomerism v0.2 ACTC1 Louise Daugherty reviewed gene: ACTC1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Brain channelopathy v1.38 CACNA1A_CAG Arianna Tucci Marked STR: CACNA1A_CAG as ready
Brain channelopathy v1.38 CACNA1A_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Brain channelopathy v1.38 CACNA1A_CAG Arianna Tucci Str: cacna1a_cag has been classified as Green List (High Evidence).
Brain channelopathy v1.38 CACNA1A_CAG Arianna Tucci Classified STR: CACNA1A_CAG as Green List (high evidence)
Brain channelopathy v1.38 CACNA1A_CAG Arianna Tucci Str: cacna1a_cag has been classified as Green List (High Evidence).
Brain channelopathy v1.37 CACNA1A_CAG Arianna Tucci STR: CACNA1A_CAG was added
STR: CACNA1A_CAG was added to Brain channelopathy. Sources: Expert Review
Mode of inheritance for STR: CACNA1A_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
STR: CACNA1A_CAG was marked as current diagnostic
Added comment: Added to the panel following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Sources: Expert Review
Hereditary spastic paraplegia v1.87 CACNA1A_CAG Arianna Tucci Marked STR: CACNA1A_CAG as ready
Hereditary spastic paraplegia v1.87 CACNA1A_CAG Arianna Tucci Added comment: Comment when marking as ready: Added to the panel following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Hereditary spastic paraplegia v1.87 CACNA1A_CAG Arianna Tucci Str: cacna1a_cag has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.87 CACNA1A_CAG Arianna Tucci Classified STR: CACNA1A_CAG as Green List (high evidence)
Hereditary spastic paraplegia v1.87 CACNA1A_CAG Arianna Tucci Str: cacna1a_cag has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.86 CACNA1A_CAG Arianna Tucci STR: CACNA1A_CAG was added
STR: CACNA1A_CAG was added to Hereditary spastic paraplegia. Sources: Expert Review
Mode of inheritance for STR: CACNA1A_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
STR: CACNA1A_CAG was marked as current diagnostic
Laterality disorders and isomerism v0.1 ZMYND10 Louise Daugherty gene: ZMYND10 was added
gene: ZMYND10 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: ZMYND10 was set to
Laterality disorders and isomerism v0.1 ZIC3 Louise Daugherty gene: ZIC3 was added
gene: ZIC3 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: ZIC3 was set to
Laterality disorders and isomerism v0.1 TTC25 Louise Daugherty gene: TTC25 was added
gene: TTC25 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: TTC25 was set to
Laterality disorders and isomerism v0.1 SPAG1 Louise Daugherty gene: SPAG1 was added
gene: SPAG1 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: SPAG1 was set to
Laterality disorders and isomerism v0.1 RSPH9 Louise Daugherty gene: RSPH9 was added
gene: RSPH9 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: RSPH9 was set to
Laterality disorders and isomerism v0.1 RSPH4A Louise Daugherty gene: RSPH4A was added
gene: RSPH4A was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: RSPH4A was set to
Laterality disorders and isomerism v0.1 RSPH3 Louise Daugherty gene: RSPH3 was added
gene: RSPH3 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: RSPH3 was set to
Laterality disorders and isomerism v0.1 RSPH1 Louise Daugherty gene: RSPH1 was added
gene: RSPH1 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: RSPH1 was set to
Laterality disorders and isomerism v0.1 PKD1L1 Louise Daugherty gene: PKD1L1 was added
gene: PKD1L1 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: PKD1L1 was set to
Laterality disorders and isomerism v0.1 PIH1D3 Louise Daugherty gene: PIH1D3 was added
gene: PIH1D3 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: PIH1D3 was set to
Laterality disorders and isomerism v0.1 NSD2 Louise Daugherty gene: NSD2 was added
gene: NSD2 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: NSD2 was set to
Laterality disorders and isomerism v0.1 NPHP4 Louise Daugherty gene: NPHP4 was added
gene: NPHP4 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: NPHP4 was set to
Laterality disorders and isomerism v0.1 NODAL Louise Daugherty gene: NODAL was added
gene: NODAL was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: NODAL was set to
Laterality disorders and isomerism v0.1 NME8 Louise Daugherty gene: NME8 was added
gene: NME8 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: NME8 was set to
Laterality disorders and isomerism v0.1 NKX2-5 Louise Daugherty gene: NKX2-5 was added
gene: NKX2-5 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: NKX2-5 was set to
Laterality disorders and isomerism v0.1 MYH6 Louise Daugherty gene: MYH6 was added
gene: MYH6 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: MYH6 was set to
Laterality disorders and isomerism v0.1 MMP21 Louise Daugherty gene: MMP21 was added
gene: MMP21 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: MMP21 was set to
Laterality disorders and isomerism v0.1 LZTFL1 Louise Daugherty gene: LZTFL1 was added
gene: LZTFL1 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: LZTFL1 was set to
Laterality disorders and isomerism v0.1 LRRC6 Louise Daugherty gene: LRRC6 was added
gene: LRRC6 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: LRRC6 was set to
Laterality disorders and isomerism v0.1 LRRC56 Louise Daugherty gene: LRRC56 was added
gene: LRRC56 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: LRRC56 was set to
Laterality disorders and isomerism v0.1 LETM1 Louise Daugherty gene: LETM1 was added
gene: LETM1 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: LETM1 was set to
Laterality disorders and isomerism v0.1 HYDIN Louise Daugherty gene: HYDIN was added
gene: HYDIN was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: HYDIN was set to
Laterality disorders and isomerism v0.1 GDF1 Louise Daugherty gene: GDF1 was added
gene: GDF1 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: GDF1 was set to
Laterality disorders and isomerism v0.1 GAS8 Louise Daugherty gene: GAS8 was added
gene: GAS8 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: GAS8 was set to
Laterality disorders and isomerism v0.1 FANCB Louise Daugherty gene: FANCB was added
gene: FANCB was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: FANCB was set to
Laterality disorders and isomerism v0.1 DRC1 Louise Daugherty gene: DRC1 was added
gene: DRC1 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: DRC1 was set to
Laterality disorders and isomerism v0.1 DNAL1 Louise Daugherty gene: DNAL1 was added
gene: DNAL1 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: DNAL1 was set to
Laterality disorders and isomerism v0.1 DNAJB13 Louise Daugherty gene: DNAJB13 was added
gene: DNAJB13 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: DNAJB13 was set to
Laterality disorders and isomerism v0.1 DNAI2 Louise Daugherty gene: DNAI2 was added
gene: DNAI2 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: DNAI2 was set to
Laterality disorders and isomerism v0.1 DNAI1 Louise Daugherty gene: DNAI1 was added
gene: DNAI1 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: DNAI1 was set to
Laterality disorders and isomerism v0.1 DNAH8 Louise Daugherty gene: DNAH8 was added
gene: DNAH8 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: DNAH8 was set to
Laterality disorders and isomerism v0.1 DNAH5 Louise Daugherty gene: DNAH5 was added
gene: DNAH5 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: DNAH5 was set to
Laterality disorders and isomerism v0.1 DNAH11 Louise Daugherty gene: DNAH11 was added
gene: DNAH11 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: DNAH11 was set to
Laterality disorders and isomerism v0.1 DNAH1 Louise Daugherty gene: DNAH1 was added
gene: DNAH1 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: DNAH1 was set to
Laterality disorders and isomerism v0.1 DNAAF5 Louise Daugherty gene: DNAAF5 was added
gene: DNAAF5 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: DNAAF5 was set to
Laterality disorders and isomerism v0.1 DNAAF4 Louise Daugherty gene: DNAAF4 was added
gene: DNAAF4 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: DNAAF4 was set to
Laterality disorders and isomerism v0.1 DNAAF3 Louise Daugherty gene: DNAAF3 was added
gene: DNAAF3 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: DNAAF3 was set to
Laterality disorders and isomerism v0.1 DNAAF2 Louise Daugherty gene: DNAAF2 was added
gene: DNAAF2 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: DNAAF2 was set to
Laterality disorders and isomerism v0.1 DNAAF1 Louise Daugherty gene: DNAAF1 was added
gene: DNAAF1 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: DNAAF1 was set to
Laterality disorders and isomerism v0.1 CRELD1 Louise Daugherty gene: CRELD1 was added
gene: CRELD1 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: CRELD1 was set to
Laterality disorders and isomerism v0.1 CFC1 Louise Daugherty gene: CFC1 was added
gene: CFC1 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: CFC1 was set to
Laterality disorders and isomerism v0.1 CFAP53 Louise Daugherty gene: CFAP53 was added
gene: CFAP53 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: CFAP53 was set to
Laterality disorders and isomerism v0.1 CCNO Louise Daugherty gene: CCNO was added
gene: CCNO was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: CCNO was set to
Laterality disorders and isomerism v0.1 CCDC65 Louise Daugherty gene: CCDC65 was added
gene: CCDC65 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: CCDC65 was set to
Laterality disorders and isomerism v0.1 CCDC40 Louise Daugherty gene: CCDC40 was added
gene: CCDC40 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: CCDC40 was set to
Laterality disorders and isomerism v0.1 CCDC39 Louise Daugherty gene: CCDC39 was added
gene: CCDC39 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: CCDC39 was set to
Laterality disorders and isomerism v0.1 CCDC151 Louise Daugherty gene: CCDC151 was added
gene: CCDC151 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: CCDC151 was set to
Laterality disorders and isomerism v0.1 CCDC114 Louise Daugherty gene: CCDC114 was added
gene: CCDC114 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: CCDC114 was set to
Laterality disorders and isomerism v0.1 CCDC103 Louise Daugherty gene: CCDC103 was added
gene: CCDC103 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: CCDC103 was set to
Laterality disorders and isomerism v0.1 C21orf59 Louise Daugherty gene: C21orf59 was added
gene: C21orf59 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: C21orf59 was set to
Laterality disorders and isomerism v0.1 C11orf70 Louise Daugherty gene: C11orf70 was added
gene: C11orf70 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: C11orf70 was set to
Laterality disorders and isomerism v0.1 ARMC4 Louise Daugherty gene: ARMC4 was added
gene: ARMC4 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: ARMC4 was set to
Laterality disorders and isomerism v0.1 ACVR2B Louise Daugherty gene: ACVR2B was added
gene: ACVR2B was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: ACVR2B was set to
Laterality disorders and isomerism v0.1 ACTG2 Louise Daugherty gene: ACTG2 was added
gene: ACTG2 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: ACTG2 was set to
Laterality disorders and isomerism v0.1 ACTC1 Louise Daugherty gene: ACTC1 was added
gene: ACTC1 was added to Laterality disorders and isomerism. Sources: NHS GMS
Mode of inheritance for gene: ACTC1 was set to
Parkinson Disease and Complex Parkinsonism v1.53 ATXN3_CAG Arianna Tucci Marked STR: ATXN3_CAG as ready
Parkinson Disease and Complex Parkinsonism v1.53 ATXN3_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Parkinson Disease and Complex Parkinsonism v1.53 ATXN3_CAG Arianna Tucci Str: atxn3_cag has been classified as Green List (High Evidence).
Parkinson Disease and Complex Parkinsonism v1.53 ATXN3_CAG Arianna Tucci Classified STR: ATXN3_CAG as Green List (high evidence)
Parkinson Disease and Complex Parkinsonism v1.53 ATXN3_CAG Arianna Tucci Str: atxn3_cag has been classified as Green List (High Evidence).
Hereditary neuropathy v1.35 ATXN3_CAG Arianna Tucci Marked STR: ATXN3_CAG as ready
Hereditary neuropathy v1.35 ATXN3_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Hereditary neuropathy v1.35 ATXN3_CAG Arianna Tucci Str: atxn3_cag has been classified as Green List (High Evidence).
Hereditary neuropathy v1.35 ATXN3_CAG Arianna Tucci Classified STR: ATXN3_CAG as Green List (high evidence)
Hereditary neuropathy v1.35 ATXN3_CAG Arianna Tucci Str: atxn3_cag has been classified as Green List (High Evidence).
Hereditary neuropathy v1.34 ATXN3_CAG Arianna Tucci Classified STR: ATXN3_CAG as Green List (high evidence)
Hereditary neuropathy v1.34 ATXN3_CAG Arianna Tucci Str: atxn3_cag has been classified as Green List (High Evidence).
Hereditary neuropathy v1.33 ATXN3_CAG Arianna Tucci STR: ATXN3_CAG was added
STR: ATXN3_CAG was added to Hereditary neuropathy. Sources: Expert Review
Mode of inheritance for STR: ATXN3_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
STR: ATXN3_CAG was marked as current diagnostic
Added comment: Added to the panel following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Sources: Expert Review
Early onset dystonia v1.55 ATXN3_CAG Arianna Tucci Marked STR: ATXN3_CAG as ready
Early onset dystonia v1.55 ATXN3_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Early onset dystonia v1.55 ATXN3_CAG Arianna Tucci Str: atxn3_cag has been classified as Green List (High Evidence).
Early onset dystonia v1.55 ATXN3_CAG Arianna Tucci Classified STR: ATXN3_CAG as Green List (high evidence)
Early onset dystonia v1.55 ATXN3_CAG Arianna Tucci Str: atxn3_cag has been classified as Green List (High Evidence).
Early onset dystonia v1.54 ATXN3_CAG Arianna Tucci STR: ATXN3_CAG was added
STR: ATXN3_CAG was added to Early onset dystonia. Sources: Expert Review
Mode of inheritance for STR: ATXN3_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for STR: ATXN3_CAG was set to GREEN
STR: ATXN3_CAG was marked as current diagnostic
Added comment: Added to the panel following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Sources: Expert Review
Hereditary spastic paraplegia v1.85 ATXN3_CAG Arianna Tucci Marked STR: ATXN3_CAG as ready
Hereditary spastic paraplegia v1.85 ATXN3_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Hereditary spastic paraplegia v1.85 ATXN3_CAG Arianna Tucci Str: atxn3_cag has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.85 ATXN3_CAG Arianna Tucci Classified STR: ATXN3_CAG as Green List (high evidence)
Hereditary spastic paraplegia v1.85 ATXN3_CAG Arianna Tucci Str: atxn3_cag has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.84 ATXN3_CAG Arianna Tucci STR: ATXN3_CAG was added
STR: ATXN3_CAG was added to Hereditary spastic paraplegia. Sources: Expert Review
Mode of inheritance for STR: ATXN3_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
STR: ATXN3_CAG was marked as current diagnostic
Hereditary ataxia v1.137 ATXN3_CAG Arianna Tucci Marked STR: ATXN3_CAG as ready
Hereditary ataxia v1.137 ATXN3_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Hereditary ataxia v1.137 ATXN3_CAG Arianna Tucci Str: atxn3_cag has been classified as Green List (High Evidence).
Hereditary ataxia v1.137 ATXN3_CAG Arianna Tucci Classified STR: ATXN3_CAG as Green List (high evidence)
Hereditary ataxia v1.137 ATXN3_CAG Arianna Tucci Str: atxn3_cag has been classified as Green List (High Evidence).
Intellectual disability v2.564 PRR12 Konstantinos Varvagiannis reviewed gene: PRR12: Rating: GREEN; Mode of pathogenicity: None; Publications: 29556724, 26163108, 28135719; Phenotypes: Global developmental delay, Intellectual disability, Abnormality of the iris, Abnormality of vision, Behavioral abnormality; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Intellectual disability v2.564 PRR12 Konstantinos Varvagiannis Deleted their review
Intellectual disability v2.564 PRR12 Konstantinos Varvagiannis gene: PRR12 was added
gene: PRR12 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: PRR12 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: PRR12 were set to 29556724; 26163108
Phenotypes for gene: PRR12 were set to Global developmental delay; Intellectual disability; Abnormality of the iris; Abnormality of vision; Behavioral abnormality
Penetrance for gene: PRR12 were set to unknown
Review for gene: PRR12 was set to GREEN
gene: PRR12 was marked as current diagnostic
Added comment: PMID: 29556724 (Leduc et al. 2018) reports on 3 unrelated individuals with de novo pathogenic variants in PRR12. The common phenotype consisted of DD/ID (3/3), iris anomalies (colobomas in 2/3 with stellate iris patern in all) as well as additional vision problems and behavioral anomalies.

3 different loss-of-function variants are reported. These variants affected the longer transcript (Ensembl ENST00000418929.6 or NM_020719 - short : ENST00000615927.1) with a single one affecting both.

PRR12 appears to be intolerant to loss-of-function muatations (pLI of 1). Some LoF variants exist in ExAC/gnomAD although the majority appear to be low-quality variants.

As commented by the authors 2 individuals with de novo variants exist in Decipher (1 in-frame deletion and a missense SNV - both variants appear in fig.2 of the article) [a few more DDD study participants in the denovo-db all from PMID: 28135719 : http://denovo-db.gs.washington.edu/denovo-db/QueryVariantServlet?searchBy=Gene&target=PRR12].

Alternative explanations for the phenotype (eg. CHARGE syndrome, etc) were ruled out in many individuals in the article.

Functional studies have not been performed. //

PMID: 26163108 (Córdova-Fletes al. 2015) is a previous report cited by Leduc et al. One individual with balanced translocation [t(10;19)] with disruption of PRR12 is described. This individual presented with ID and behavioral anomalies (without details on eventual coloboma or other iris anomalies).

The translocation was balanced and led to fusion of PRR12 with LMIZ1. The breakpoint was located within intron 11 (PRR12 is a 14-exon gene) with fusion of PRR12 exon 11 with ZMIZ1 exon 8 upon RT-PCR. Both PRR12/ZMIZ1 products were predicted to be truncated due to frameshift and introduction of premature stop codon.

[Surprisingly qPCR and Western blot in patient LCLs were suggestive of increased PRR12 expression compared to controls suggesting either a compensation mechanism or longer half-life/accumulation of the aberrant PRR12].

Expression of wt PRR12 was highest during embryonic development in mouse/rat brain cells suggesting a role in early CNS development. The transcript studied (corresponding to the longest human transcript) was exclusively located in the nucleus compared to a shorter one located primary in the nucleus but also outside suggesting that PRR12 might be involved in regulation of transcription.

In line with this several genes linked to neurodevelopmental processes/neuronal communication appeared be dysregulated in lymphoblastoid cell lines (LCLs) from the translocation patient.

A role for ZMIZ1 is similarly discussed. //

PRR12 is included in gene panels for ID offered by diagnostic laboratories. //

As a result, this gene can be considered for inclusion in this panel as green (or amber).
Sources: Literature
Hereditary neuropathy v1.32 ATXN2_CAG Arianna Tucci Marked STR: ATXN2_CAG as ready
Hereditary neuropathy v1.32 ATXN2_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Hereditary neuropathy v1.32 ATXN2_CAG Arianna Tucci Str: atxn2_cag has been classified as Green List (High Evidence).
Hereditary neuropathy v1.32 ATXN2_CAG Arianna Tucci Classified STR: ATXN2_CAG as Green List (high evidence)
Hereditary neuropathy v1.32 ATXN2_CAG Arianna Tucci Str: atxn2_cag has been classified as Green List (High Evidence).
Hereditary neuropathy v1.32 ATXN2_CAG Arianna Tucci Classified STR: ATXN2_CAG as Green List (high evidence)
Hereditary neuropathy v1.32 ATXN2_CAG Arianna Tucci Str: atxn2_cag has been classified as Green List (High Evidence).
Hereditary neuropathy v1.31 ATXN2_CAG Arianna Tucci STR: ATXN2_CAG was added
STR: ATXN2_CAG was added to Hereditary neuropathy. Sources: Expert Review
Mode of inheritance for STR: ATXN2_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for STR: ATXN2_CAG was set to GREEN
STR: ATXN2_CAG was marked as current diagnostic
Added comment: Sources: Expert Review
Early onset dystonia v1.53 ATXN2_CAG Arianna Tucci Marked STR: ATXN2_CAG as ready
Early onset dystonia v1.53 ATXN2_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Early onset dystonia v1.53 ATXN2_CAG Arianna Tucci Str: atxn2_cag has been classified as Green List (High Evidence).
Early onset dystonia v1.53 ATXN2_CAG Arianna Tucci Classified STR: ATXN2_CAG as Green List (high evidence)
Early onset dystonia v1.53 ATXN2_CAG Arianna Tucci Str: atxn2_cag has been classified as Green List (High Evidence).
Early onset dystonia v1.52 ATXN2_CAG Arianna Tucci STR: ATXN2_CAG was added
STR: ATXN2_CAG was added to Early onset dystonia. Sources: Expert Review
Mode of inheritance for STR: ATXN2_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for STR: ATXN2_CAG was set to GREEN
STR: ATXN2_CAG was marked as current diagnostic
Added comment: Sources: Expert Review
Early onset or syndromic epilepsy v0.1396 PMM2 Eleanor Williams Classified gene: PMM2 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1396 PMM2 Eleanor Williams Added comment: Comment on list classification: > 3 cases of variants in this gene associated with the phenotype, and presenting with seizures.
Early onset or syndromic epilepsy v0.1396 PMM2 Eleanor Williams Gene: pmm2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1395 PMM2 Eleanor Williams Classified gene: PMM2 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1395 PMM2 Eleanor Williams Added comment: Comment on list classification: > 3 cases associating variants in this gene with the phenotype and presenting with seizures.
Early onset or syndromic epilepsy v0.1395 PMM2 Eleanor Williams Gene: pmm2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1394 PMM2 Eleanor Williams Marked gene: PMM2 as ready
Early onset or syndromic epilepsy v0.1394 PMM2 Eleanor Williams Gene: pmm2 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1394 PMM2 Eleanor Williams Mode of inheritance for gene: PMM2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1393 PMM2 Eleanor Williams Phenotypes for gene: PMM2 were changed from to Congenital disorder of glycosylation, type Ia 212065
Early onset or syndromic epilepsy v0.1392 PMM2 Eleanor Williams Publications for gene: PMM2 were set to
Early onset or syndromic epilepsy v0.1391 PMM2 Eleanor Williams commented on gene: PMM2
Early onset or syndromic epilepsy v0.1391 POMGNT1 Eleanor Williams Marked gene: POMGNT1 as ready
Early onset or syndromic epilepsy v0.1391 POMGNT1 Eleanor Williams Gene: pomgnt1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1391 POMGNT1 Eleanor Williams Phenotypes for gene: POMGNT1 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3 253280
Early onset or syndromic epilepsy v0.1390 POMGNT1 Eleanor Williams Mode of inheritance for gene: POMGNT1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1389 POMGNT1 Eleanor Williams Publications for gene: POMGNT1 were set to
Early onset or syndromic epilepsy v0.1388 POMGNT1 Eleanor Williams Classified gene: POMGNT1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1388 POMGNT1 Eleanor Williams Added comment: Comment on list classification: > 3 cases with variants in this gene and seizures so rating green.
Early onset or syndromic epilepsy v0.1388 POMGNT1 Eleanor Williams Gene: pomgnt1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1387 POMGNT1 Eleanor Williams commented on gene: POMGNT1
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.28 ATXN2_CAG Arianna Tucci Marked STR: ATXN2_CAG as ready
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.28 ATXN2_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.28 ATXN2_CAG Arianna Tucci Str: atxn2_cag has been classified as Green List (High Evidence).
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.28 ATXN2_CAG Arianna Tucci Classified STR: ATXN2_CAG as Green List (high evidence)
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.28 ATXN2_CAG Arianna Tucci Str: atxn2_cag has been classified as Green List (High Evidence).
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.27 ATXN2_CAG Arianna Tucci STR: ATXN2_CAG was added
STR: ATXN2_CAG was added to Early onset dementia (encompassing fronto-temporal dementia and prion disease). Sources: Expert Review
Mode of inheritance for STR: ATXN2_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for STR: ATXN2_CAG was set to GREEN
STR: ATXN2_CAG was marked as current diagnostic
Added comment: Sources: Expert Review
Hereditary spastic paraplegia v1.83 ATXN2_CAG Arianna Tucci Classified STR: ATXN2_CAG as Green List (high evidence)
Hereditary spastic paraplegia v1.83 ATXN2_CAG Arianna Tucci Str: atxn2_cag has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.82 ATXN2_CAG Arianna Tucci STR: ATXN2_CAG was added
STR: ATXN2_CAG was added to Hereditary spastic paraplegia. Sources: Expert Review
Mode of inheritance for STR: ATXN2_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added comment: Added to the panel following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Sources: Expert Review
Parkinson Disease and Complex Parkinsonism v1.52 ATXN2_CAG Arianna Tucci Marked STR: ATXN2_CAG as ready
Parkinson Disease and Complex Parkinsonism v1.52 ATXN2_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Parkinson Disease and Complex Parkinsonism v1.52 ATXN2_CAG Arianna Tucci Str: atxn2_cag has been classified as Green List (High Evidence).
Parkinson Disease and Complex Parkinsonism v1.52 ATXN2_CAG Arianna Tucci Classified STR: ATXN2_CAG as Green List (high evidence)
Parkinson Disease and Complex Parkinsonism v1.52 ATXN2_CAG Arianna Tucci Str: atxn2_cag has been classified as Green List (High Evidence).
Hereditary ataxia v1.136 ATXN2_CAG Arianna Tucci Marked STR: ATXN2_CAG as ready
Hereditary ataxia v1.136 ATXN2_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Hereditary ataxia v1.136 ATXN2_CAG Arianna Tucci Str: atxn2_cag has been classified as Green List (High Evidence).
Hereditary ataxia v1.136 ATXN2_CAG Arianna Tucci Classified STR: ATXN2_CAG as Green List (high evidence)
Hereditary ataxia v1.136 ATXN2_CAG Arianna Tucci Str: atxn2_cag has been classified as Green List (High Evidence).
Hereditary ataxia v1.135 ATXN2 Arianna Tucci Deleted their review
Hereditary ataxia v1.135 ATXN2 Arianna Tucci reviewed gene: ATXN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy v1.30 ATXN1_CAG Arianna Tucci Marked STR: ATXN1_CAG as ready
Hereditary neuropathy v1.30 ATXN1_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Hereditary neuropathy v1.30 ATXN1_CAG Arianna Tucci Str: atxn1_cag has been classified as Green List (High Evidence).
Hereditary neuropathy v1.30 ATXN1_CAG Arianna Tucci Classified STR: ATXN1_CAG as Green List (high evidence)
Hereditary neuropathy v1.30 ATXN1_CAG Arianna Tucci Str: atxn1_cag has been classified as Green List (High Evidence).
Hereditary neuropathy v1.29 ATXN1_CAG Arianna Tucci STR: ATXN1_CAG was added
STR: ATXN1_CAG was added to Hereditary neuropathy. Sources: Expert Review
Mode of inheritance for STR: ATXN1_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for STR: ATXN1_CAG was set to GREEN
STR: ATXN1_CAG was marked as clinically relevant
STR: ATXN1_CAG was marked as current diagnostic
Added comment: Added to the panel following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Sources: Expert Review
Hereditary spastic paraplegia v1.81 ATXN1_CAG Arianna Tucci Marked STR: ATXN1_CAG as ready
Hereditary spastic paraplegia v1.81 ATXN1_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Hereditary spastic paraplegia v1.81 ATXN1_CAG Arianna Tucci Str: atxn1_cag has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.81 ATXN1_CAG Arianna Tucci Classified STR: ATXN1_CAG as Green List (high evidence)
Hereditary spastic paraplegia v1.81 ATXN1_CAG Arianna Tucci Str: atxn1_cag has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.80 ATXN1_CAG Arianna Tucci STR: ATXN1_CAG was added
STR: ATXN1_CAG was added to Hereditary spastic paraplegia. Sources: Expert Review
Mode of inheritance for STR: ATXN1_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for STR: ATXN1_CAG was set to GREEN
Added comment: Sources: Expert Review
Parkinson Disease and Complex Parkinsonism v1.51 ATXN1_CAG Arianna Tucci Marked STR: ATXN1_CAG as ready
Parkinson Disease and Complex Parkinsonism v1.51 ATXN1_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Parkinson Disease and Complex Parkinsonism v1.51 ATXN1_CAG Arianna Tucci Str: atxn1_cag has been classified as Green List (High Evidence).
Parkinson Disease and Complex Parkinsonism v1.51 ATXN1_CAG Arianna Tucci Classified STR: ATXN1_CAG as Green List (high evidence)
Parkinson Disease and Complex Parkinsonism v1.51 ATXN1_CAG Arianna Tucci Str: atxn1_cag has been classified as Green List (High Evidence).
Parkinson Disease and Complex Parkinsonism v1.50 ATXN1_CAG Arianna Tucci STR: ATXN1_CAG was added
STR: ATXN1_CAG was added to Parkinson Disease and Complex Parkinsonism. Sources: Expert Review
Mode of inheritance for STR: ATXN1_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
STR: ATXN1_CAG was marked as clinically relevant
STR: ATXN1_CAG was marked as current diagnostic
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.26 ATXN1_CAG Arianna Tucci Marked STR: ATXN1_CAG as ready
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.26 ATXN1_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.26 ATXN1_CAG Arianna Tucci Str: atxn1_cag has been classified as Green List (High Evidence).
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.26 ATXN1_CAG Arianna Tucci Classified STR: ATXN1_CAG as Green List (high evidence)
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.26 ATXN1_CAG Arianna Tucci Str: atxn1_cag has been classified as Green List (High Evidence).
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.25 ATXN1_CAG Arianna Tucci STR: ATXN1_CAG was added
STR: ATXN1_CAG was added to Early onset dementia (encompassing fronto-temporal dementia and prion disease). Sources: Expert Review
Mode of inheritance for STR: ATXN1_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for STR: ATXN1_CAG was set to GREEN
STR: ATXN1_CAG was marked as clinically relevant
STR: ATXN1_CAG was marked as current diagnostic
Added comment: Sources: Expert Review
Hereditary ataxia v1.135 ATXN1_CAG Arianna Tucci Marked STR: ATXN1_CAG as ready
Hereditary ataxia v1.135 ATXN1_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Hereditary ataxia v1.135 ATXN1_CAG Arianna Tucci Str: atxn1_cag has been classified as Green List (High Evidence).
Hereditary ataxia v1.135 ATXN1_CAG Arianna Tucci Classified STR: ATXN1_CAG as Green List (high evidence)
Hereditary ataxia v1.135 ATXN1_CAG Arianna Tucci Str: atxn1_cag has been classified as Green List (High Evidence).
Hereditary ataxia v1.134 ATXN1_CAG Arianna Tucci Pathogenic Number of Repeats for ATXN1_CAG was changed from 39 to 44.
Brain channelopathy v1.36 CSTB_CCCCGCCCCGCG Arianna Tucci Marked STR: CSTB_CCCCGCCCCGCG as ready
Brain channelopathy v1.36 CSTB_CCCCGCCCCGCG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Brain channelopathy v1.36 CSTB_CCCCGCCCCGCG Arianna Tucci Str: cstb_ccccgccccgcg has been classified as Green List (High Evidence).
Brain channelopathy v1.36 CSTB_CCCCGCCCCGCG Arianna Tucci Classified STR: CSTB_CCCCGCCCCGCG as Green List (high evidence)
Brain channelopathy v1.36 CSTB_CCCCGCCCCGCG Arianna Tucci Str: cstb_ccccgccccgcg has been classified as Green List (High Evidence).
Brain channelopathy v1.35 CSTB_CCCCGCCCCGCG Arianna Tucci STR: CSTB_CCCCGCCCCGCG was added
STR: CSTB_CCCCGCCCCGCG was added to Brain channelopathy. Sources: Expert Review
Mode of inheritance for STR: CSTB_CCCCGCCCCGCG was set to BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia v1.133 CSTB_CCCCGCCCCGCG Arianna Tucci Marked STR: CSTB_CCCCGCCCCGCG as ready
Hereditary ataxia v1.133 CSTB_CCCCGCCCCGCG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Hereditary ataxia v1.133 CSTB_CCCCGCCCCGCG Arianna Tucci Str: cstb_ccccgccccgcg has been classified as Green List (High Evidence).
Hereditary ataxia v1.133 CSTB_CCCCGCCCCGCG Arianna Tucci Classified STR: CSTB_CCCCGCCCCGCG as Green List (high evidence)
Hereditary ataxia v1.133 CSTB_CCCCGCCCCGCG Arianna Tucci Str: cstb_ccccgccccgcg has been classified as Green List (High Evidence).
Hereditary ataxia v1.132 CSTB_CCCCGCCCCGCG Arianna Tucci STR: CSTB_CCCCGCCCCGCG was added
STR: CSTB_CCCCGCCCCGCG was added to Hereditary ataxia. Sources: Expert Review
Mode of inheritance for STR: CSTB_CCCCGCCCCGCG was set to BIALLELIC, autosomal or pseudoautosomal
Added comment: Added to the panel following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Sources: Expert Review
Early onset or syndromic epilepsy v0.1387 PPT1 Eleanor Williams Marked gene: PPT1 as ready
Early onset or syndromic epilepsy v0.1387 PPT1 Eleanor Williams Added comment: Comment when marking as ready: Sufficient cases
Early onset or syndromic epilepsy v0.1387 PPT1 Eleanor Williams Gene: ppt1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1387 PPT1 Eleanor Williams Phenotypes for gene: PPT1 were changed from to Ceroid lipofuscinosis, neuronal, 1 256730
Early onset or syndromic epilepsy v0.1386 PPT1 Eleanor Williams Publications for gene: PPT1 were set to
Early onset or syndromic epilepsy v0.1385 PPT1 Eleanor Williams Mode of inheritance for gene: PPT1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1384 PPT1 Eleanor Williams Classified gene: PPT1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1384 PPT1 Eleanor Williams Added comment: Comment on list classification: Numerous variants and cases presenting with seizures.
Early onset or syndromic epilepsy v0.1384 PPT1 Eleanor Williams Gene: ppt1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1383 PPT1 Eleanor Williams commented on gene: PPT1
Early onset or syndromic epilepsy v0.1383 PROSC Eleanor Williams Marked gene: PROSC as ready
Early onset or syndromic epilepsy v0.1383 PROSC Eleanor Williams Added comment: Comment when marking as ready: > 3 cases
Early onset or syndromic epilepsy v0.1383 PROSC Eleanor Williams Gene: prosc has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1383 PROSC Eleanor Williams Phenotypes for gene: PROSC were changed from to Epilepsy, early-onset, vitamin B6-dependent 617290
Early onset or syndromic epilepsy v0.1382 PROSC Eleanor Williams Publications for gene: PROSC were set to
Early onset or syndromic epilepsy v0.1381 PROSC Eleanor Williams Mode of inheritance for gene: PROSC was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1380 PROSC Eleanor Williams Classified gene: PROSC as Green List (high evidence)
Early onset or syndromic epilepsy v0.1380 PROSC Eleanor Williams Added comment: Comment on list classification: > 3 cases reported
Early onset or syndromic epilepsy v0.1380 PROSC Eleanor Williams Gene: prosc has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1379 PROSC Eleanor Williams commented on gene: PROSC
Early onset or syndromic epilepsy v0.1379 PROSC Eleanor Williams Tag new-gene-name tag was added to gene: PROSC.
Early onset or syndromic epilepsy v0.1379 NARS2 Louise Daugherty Marked gene: NARS2 as ready
Early onset or syndromic epilepsy v0.1379 NARS2 Louise Daugherty Gene: nars2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1379 NARS2 Louise Daugherty Classified gene: NARS2 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1379 NARS2 Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotypes, sufficient cases, and external review comment all support gene-disease association.
Early onset or syndromic epilepsy v0.1379 NARS2 Louise Daugherty Gene: nars2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1378 NARS2 Louise Daugherty Added comment: Comment on publications: Added publications to support upgrading of the gene to Green
Early onset or syndromic epilepsy v0.1378 NARS2 Louise Daugherty Publications for gene: NARS2 were set to
Early onset or syndromic epilepsy v0.1377 SIX3 Sarah Leigh Added comment: Comment on publications: Variants reported in following articles in either Holoprosencephaly 2 157170 or Schizencephaly 269160 however, seizures are not mentioned in the patients being reported PMID: 19353631, 17001667, 10369266, 15523651.
Early onset or syndromic epilepsy v0.1377 SIX3 Sarah Leigh Publications for gene: SIX3 were set to 28670735; 20157829
Early onset or syndromic epilepsy v0.1376 PTEN Eleanor Williams Phenotypes for gene: PTEN were changed from to Cowden syndrome 1 158350; Lhermitte-Duclos syndrome; BANNAYAN-RILEY-RUVALCABA SYNDROME
Early onset or syndromic epilepsy v0.1375 PTEN Eleanor Williams Marked gene: PTEN as ready
Early onset or syndromic epilepsy v0.1375 PTEN Eleanor Williams Gene: pten has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1375 PTEN Eleanor Williams Mode of inheritance for gene: PTEN was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v0.1374 PTEN Eleanor Williams Publications for gene: PTEN were set to
Early onset or syndromic epilepsy v0.1373 PTEN Eleanor Williams Classified gene: PTEN as Green List (high evidence)
Early onset or syndromic epilepsy v0.1373 PTEN Eleanor Williams Added comment: Comment on list classification: 3 cases in which a variant in PTEN is reported in individuals with Bannayan-Riley-Ruvalcaba syndrome with clinical phenotype that includes seizures.
Early onset or syndromic epilepsy v0.1373 PTEN Eleanor Williams Gene: pten has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1372 NARS2 Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Early onset or syndromic epilepsy v0.1372 NARS2 Louise Daugherty Phenotypes for gene: NARS2 were changed from to Combined oxidative phosphorylation deficiency 24, 616239; seizures
Early onset or syndromic epilepsy v0.1371 PTEN Eleanor Williams commented on gene: PTEN
Early onset or syndromic epilepsy v0.1371 MTHFR Louise Daugherty Marked gene: MTHFR as ready
Early onset or syndromic epilepsy v0.1371 MTHFR Louise Daugherty Gene: mthfr has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1371 MTR Louise Daugherty Marked gene: MTR as ready
Early onset or syndromic epilepsy v0.1371 MTR Louise Daugherty Gene: mtr has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1371 NAGA Louise Daugherty Marked gene: NAGA as ready
Early onset or syndromic epilepsy v0.1371 NAGA Louise Daugherty Gene: naga has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1371 NAGA Louise Daugherty Classified gene: NAGA as Green List (high evidence)
Early onset or syndromic epilepsy v0.1371 NAGA Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association.
Early onset or syndromic epilepsy v0.1371 NAGA Louise Daugherty Gene: naga has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1370 NAGA Louise Daugherty Added comment: Comment on publications: Added publications to support gene-disease association, and upgrading of the gene to Green
Early onset or syndromic epilepsy v0.1370 NAGA Louise Daugherty Publications for gene: NAGA were set to
Early onset or syndromic epilepsy v0.1369 SIX3 Sarah Leigh Publications for gene: SIX3 were set to
Early onset or syndromic epilepsy v0.1368 SIX3 Sarah Leigh Source Victorian Clinical Genetics Services was removed from SIX3.
Source Literature was added to SIX3.
Penetrance for gene SIX3 was set from to None
Limb disorders v0.350 ORC1 Eleanor Williams Marked gene: ORC1 as ready
Limb disorders v0.350 ORC1 Eleanor Williams Added comment: Comment when marking as ready: checked by clinical team
Limb disorders v0.350 ORC1 Eleanor Williams Gene: orc1 has been classified as Amber List (Moderate Evidence).
Limb disorders v0.350 ORC1 Eleanor Williams commented on gene: ORC1: Genomics England clinical team agree with Amber rating since Meier-Gorlin is a phenotype associated with generalised short stature and microcephaly rather than more focal limb phenotype. It is more likely to be picked up via other panels such as Primary Microcephaly - Microcephalic Dwarfism Spectrum and Unexplained skeletal dysplasia panels.
Early onset or syndromic epilepsy v0.1367 PCCB Eleanor Williams Classified gene: PCCB as Green List (high evidence)
Early onset or syndromic epilepsy v0.1367 PCCB Eleanor Williams Added comment: Comment on list classification: Promoted to green on the basis that there are sufficient cases of variants in this gene in patients with a relevant phenotype, and that seizures are reported in 12-53% of patients.
Early onset or syndromic epilepsy v0.1367 PCCB Eleanor Williams Gene: pccb has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1366 PCCA Eleanor Williams Classified gene: PCCA as Green List (high evidence)
Early onset or syndromic epilepsy v0.1366 PCCA Eleanor Williams Added comment: Comment on list classification: Promoted to green on the basis that there are sufficient cases of variants in this gene in patients with a relevant phenotype, and that seizures are reported in 12-53% of patients.
Early onset or syndromic epilepsy v0.1366 PCCA Eleanor Williams Gene: pcca has been classified as Green List (High Evidence).
Parkinson Disease and Complex Parkinsonism v1.49 ATN1_CAG Arianna Tucci Marked STR: ATN1_CAG as ready
Parkinson Disease and Complex Parkinsonism v1.49 ATN1_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with GMC experts (6/09/2018) about feeding back STR results
Parkinson Disease and Complex Parkinsonism v1.49 ATN1_CAG Arianna Tucci Str: atn1_cag has been classified as Red List (Low Evidence).
Parkinson Disease and Complex Parkinsonism v1.49 ATN1_CAG Arianna Tucci STR: ATN1_CAG was added
STR: ATN1_CAG was added to Parkinson Disease and Complex Parkinsonism. Sources: Expert Review
Mode of inheritance for STR: ATN1_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Brain channelopathy v1.34 ATN1_CAG Arianna Tucci Marked STR: ATN1_CAG as ready
Brain channelopathy v1.34 ATN1_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with GMC experts (6/09/2018) about feeding back STR results
Brain channelopathy v1.34 ATN1_CAG Arianna Tucci Str: atn1_cag has been classified as Green List (High Evidence).
Brain channelopathy v1.34 ATN1_CAG Arianna Tucci Classified STR: ATN1_CAG as Green List (high evidence)
Brain channelopathy v1.34 ATN1_CAG Arianna Tucci Str: atn1_cag has been classified as Green List (High Evidence).
Early onset dystonia v1.51 JPH3_CTG Arianna Tucci Marked STR: JPH3_CTG as ready
Early onset dystonia v1.51 JPH3_CTG Arianna Tucci Added comment: Comment when marking as ready: Added to the panel following the Webex discussion with GMC experts (6/09/2018) about feeding back STR results
Early onset dystonia v1.51 JPH3_CTG Arianna Tucci Str: jph3_ctg has been classified as Green List (High Evidence).
Early onset dystonia v1.51 JPH3_CTG Arianna Tucci Classified STR: JPH3_CTG as Green List (high evidence)
Early onset dystonia v1.51 JPH3_CTG Arianna Tucci Str: jph3_ctg has been classified as Green List (High Evidence).
Early onset dystonia v1.50 JPH3_CTG Arianna Tucci STR: JPH3_CTG was added
STR: JPH3_CTG was added to Early onset dystonia. Sources: Expert Review
Mode of inheritance for STR: JPH3_CTG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for STR: JPH3_CTG was set to GREEN
Added comment: Added to the panel following the Webex discussion with GMC experts (6/09/2018) about feeding back STR results
Sources: Expert Review
Parkinson Disease and Complex Parkinsonism v1.48 JPH3_CTG Arianna Tucci Classified STR: JPH3_CTG as Green List (high evidence)
Parkinson Disease and Complex Parkinsonism v1.48 JPH3_CTG Arianna Tucci Str: jph3_ctg has been classified as Green List (High Evidence).
Parkinson Disease and Complex Parkinsonism v1.47 JPH3_CTG Arianna Tucci Marked STR: JPH3_CTG as ready
Parkinson Disease and Complex Parkinsonism v1.47 JPH3_CTG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with GMC experts (6/09/2018) about feeding back STR results
Parkinson Disease and Complex Parkinsonism v1.47 JPH3_CTG Arianna Tucci Str: jph3_ctg has been classified as Red List (Low Evidence).
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.24 HTT_CAG Arianna Tucci Marked STR: HTT_CAG as ready
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.24 HTT_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with HD experts (6/09/2018) about feeding back HTT results
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.24 HTT_CAG Arianna Tucci Str: htt_cag has been classified as Green List (High Evidence).
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.24 HTT_CAG Arianna Tucci Classified STR: HTT_CAG as Green List (high evidence)
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.24 HTT_CAG Arianna Tucci Str: htt_cag has been classified as Green List (High Evidence).
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.23 HTT_CAG Arianna Tucci STR: HTT_CAG was added
STR: HTT_CAG was added to Early onset dementia (encompassing fronto-temporal dementia and prion disease). Sources: Expert Review
Mode of inheritance for STR: HTT_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for STR: HTT_CAG was set to GREEN
Added comment: Added to the panel following the Webex discussion with HD experts (6/09/2018) about feeding back HTT results
Sources: Expert Review
Hereditary ataxia v1.131 HTT_CAG Arianna Tucci Marked STR: HTT_CAG as ready
Hereditary ataxia v1.131 HTT_CAG Arianna Tucci Added comment: Comment when marking as ready: Added to the panel following the Webex discussion with HD experts (6/09/2018) about feeding back HTT results
Hereditary ataxia v1.131 HTT_CAG Arianna Tucci Str: htt_cag has been classified as Green List (High Evidence).
Hereditary ataxia v1.131 HTT_CAG Arianna Tucci Classified STR: HTT_CAG as Green List (high evidence)
Hereditary ataxia v1.131 HTT_CAG Arianna Tucci Str: htt_cag has been classified as Green List (High Evidence).
Hereditary ataxia v1.130 HTT_CAG Arianna Tucci STR: HTT_CAG was added
STR: HTT_CAG was added to Hereditary ataxia. Sources: Expert Review
Mode of inheritance for STR: HTT_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
STR: HTT_CAG was marked as current diagnostic
Hereditary spastic paraplegia v1.79 HTT_CAG Arianna Tucci Marked STR: HTT_CAG as ready
Hereditary spastic paraplegia v1.79 HTT_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as green following the Webex discussion with HD experts (6/09/2018) about feeding back HTT results
Hereditary spastic paraplegia v1.79 HTT_CAG Arianna Tucci Str: htt_cag has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.79 HTT_CAG Arianna Tucci Classified STR: HTT_CAG as Green List (high evidence)
Hereditary spastic paraplegia v1.79 HTT_CAG Arianna Tucci Str: htt_cag has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.78 HTT_CAG Arianna Tucci Pathogenic Number of Repeats for HTT_CAG was changed from 37 to 40.
Hereditary spastic paraplegia v1.77 HTT_CAG Arianna Tucci Pathogenic Number of Repeats for HTT_CAG was changed from 38 to 37.
Hereditary spastic paraplegia v1.75 HTT_CAG Arianna Tucci STR: HTT_CAG was added
STR: HTT_CAG was added to Hereditary spastic paraplegia. Sources: Expert Review
Mode of inheritance for STR: HTT_CAG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Review for STR: HTT_CAG was set to GREEN
Added comment: Added to the panel following the Webex discussion with GMC experts (6/09/2018) about feeding back HTT results
Sources: Expert Review
Parkinson Disease and Complex Parkinsonism v1.47 HTT_CAG Arianna Tucci commented on STR: HTT_CAG: Threshold changes to 40 repeats following the Webex discussion with HD experts (6/09/2018) about feeding back HTT results
Parkinson Disease and Complex Parkinsonism v1.47 HTT_CAG Arianna Tucci Marked STR: HTT_CAG as ready
Parkinson Disease and Complex Parkinsonism v1.47 HTT_CAG Arianna Tucci Str: htt_cag has been classified as Green List (High Evidence).
Parkinson Disease and Complex Parkinsonism v1.47 HTT_CAG Arianna Tucci Normal Number of Repeats for HTT_CAG was changed from 36 to 40.
Pathogenic Number of Repeats for HTT_CAG was changed from 36 to 40.
Congenital myopathy v1.65 AR_CAG Arianna Tucci Marked STR: AR_CAG as ready
Congenital myopathy v1.65 AR_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Congenital myopathy v1.65 AR_CAG Arianna Tucci Str: ar_cag has been classified as Green List (High Evidence).
Congenital myopathy v1.65 AR_CAG Arianna Tucci Classified STR: AR_CAG as Green List (high evidence)
Congenital myopathy v1.65 AR_CAG Arianna Tucci Str: ar_cag has been classified as Green List (High Evidence).
Congenital myopathy v1.64 AR_CAG Arianna Tucci STR: AR_CAG was added
STR: AR_CAG was added to Congenital myopathy. Sources: Expert list
Mode of inheritance for STR: AR_CAG was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
STR: AR_CAG was marked as current diagnostic
Added comment: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Sources: Expert list
Distal myopathies v1.9 AR_CAG Arianna Tucci Marked STR: AR_CAG as ready
Distal myopathies v1.9 AR_CAG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Distal myopathies v1.9 AR_CAG Arianna Tucci Str: ar_cag has been classified as Green List (High Evidence).
Distal myopathies v1.9 AR_CAG Arianna Tucci Classified STR: AR_CAG as Green List (high evidence)
Distal myopathies v1.9 AR_CAG Arianna Tucci Str: ar_cag has been classified as Green List (High Evidence).
Distal myopathies v1.8 AR_CAG Arianna Tucci STR: AR_CAG was added
STR: AR_CAG was added to Distal myopathies. Sources: Expert list
Mode of inheritance for STR: AR_CAG was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
STR: AR_CAG was marked as current diagnostic
Paediatric motor neuronopathies v1.17 AR_CAG Arianna Tucci Marked STR: AR_CAG as ready
Paediatric motor neuronopathies v1.17 AR_CAG Arianna Tucci Str: ar_cag has been classified as Red List (Low Evidence).
Paediatric motor neuronopathies v1.17 AR_CAG Arianna Tucci Marked STR: AR_CAG as ready
Paediatric motor neuronopathies v1.17 AR_CAG Arianna Tucci Str: ar_cag has been classified as Red List (Low Evidence).
Paediatric motor neuronopathies v1.17 AR_CAG Arianna Tucci Classified STR: AR_CAG as Red List (low evidence)
Paediatric motor neuronopathies v1.17 AR_CAG Arianna Tucci Str: ar_cag has been classified as Red List (Low Evidence).
Parkinson Disease and Complex Parkinsonism v1.46 C9orf72_GGGGCC Arianna Tucci Marked STR: C9orf72_GGGGCC as ready
Parkinson Disease and Complex Parkinsonism v1.46 C9orf72_GGGGCC Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Parkinson Disease and Complex Parkinsonism v1.46 C9orf72_GGGGCC Arianna Tucci Str: c9orf72_ggggcc has been classified as Green List (High Evidence).
Parkinson Disease and Complex Parkinsonism v1.46 C9orf72_GGGGCC Arianna Tucci Classified STR: C9orf72_GGGGCC as Green List (high evidence)
Parkinson Disease and Complex Parkinsonism v1.46 C9orf72_GGGGCC Arianna Tucci Str: c9orf72_ggggcc has been classified as Green List (High Evidence).
Mitochondrial disorders v1.73 FXN_GAA Arianna Tucci Marked STR: FXN_GAA as ready
Mitochondrial disorders v1.73 FXN_GAA Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Mitochondrial disorders v1.73 FXN_GAA Arianna Tucci Str: fxn_gaa has been classified as Green List (High Evidence).
Mitochondrial disorders v1.73 FXN_GAA Arianna Tucci Classified STR: FXN_GAA as Green List (high evidence)
Mitochondrial disorders v1.73 FXN_GAA Arianna Tucci Str: fxn_gaa has been classified as Green List (High Evidence).
Mitochondrial disorders v1.72 FXN_GAA Arianna Tucci STR: FXN_GAA was added
STR: FXN_GAA was added to Mitochondrial disorders. Sources: Expert Review
Mode of inheritance for STR: FXN_GAA was set to BIALLELIC, autosomal or pseudoautosomal
Review for STR: FXN_GAA was set to GREEN
Added comment: Added to the panel following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Sources: Expert Review
Hereditary neuropathy v1.28 FXN_GAA Arianna Tucci Marked STR: FXN_GAA as ready
Hereditary neuropathy v1.28 FXN_GAA Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Hereditary neuropathy v1.28 FXN_GAA Arianna Tucci Str: fxn_gaa has been classified as Green List (High Evidence).
Hereditary neuropathy v1.28 FXN_GAA Arianna Tucci Classified STR: FXN_GAA as Green List (high evidence)
Hereditary neuropathy v1.28 FXN_GAA Arianna Tucci Str: fxn_gaa has been classified as Green List (High Evidence).
Hereditary neuropathy v1.28 FXN_GAA Arianna Tucci Classified STR: FXN_GAA as Green List (high evidence)
Hereditary neuropathy v1.28 FXN_GAA Arianna Tucci Str: fxn_gaa has been classified as Green List (High Evidence).
Hereditary neuropathy v1.27 FXN_GAA Arianna Tucci STR: FXN_GAA was added
STR: FXN_GAA was added to Hereditary neuropathy. Sources: Expert Review
Mode of inheritance for STR: FXN_GAA was set to BIALLELIC, autosomal or pseudoautosomal
Review for STR: FXN_GAA was set to GREEN
Added comment: Added to the panel following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Sources: Expert Review
Hereditary spastic paraplegia v1.74 FXN_GAA Arianna Tucci Marked STR: FXN_GAA as ready
Hereditary spastic paraplegia v1.74 FXN_GAA Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Hereditary spastic paraplegia v1.74 FXN_GAA Arianna Tucci Str: fxn_gaa has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.74 FXN_GAA Arianna Tucci Classified STR: FXN_GAA as Green List (high evidence)
Hereditary spastic paraplegia v1.74 FXN_GAA Arianna Tucci Str: fxn_gaa has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.73 FXN_GAA Arianna Tucci STR: FXN_GAA was added
STR: FXN_GAA was added to Hereditary spastic paraplegia. Sources: Expert Review
Mode of inheritance for STR: FXN_GAA was set to BIALLELIC, autosomal or pseudoautosomal
STR: FXN_GAA was marked as current diagnostic
Added comment: Added to the panel following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Sources: Expert Review
Hereditary ataxia v1.129 FXN_GAA Arianna Tucci Normal Number of Repeats for FXN_GAA was changed from 42 to 44.
Rating Changed from Green List (high evidence) to Green List (high evidence)
Hereditary ataxia v1.128 FXN_GAA Arianna Tucci Marked STR: FXN_GAA as ready
Hereditary ataxia v1.128 FXN_GAA Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Hereditary ataxia v1.128 FXN_GAA Arianna Tucci Str: fxn_gaa has been classified as Green List (High Evidence).
Hereditary ataxia v1.128 FXN_GAA Arianna Tucci Classified STR: FXN_GAA as Green List (high evidence)
Hereditary ataxia v1.128 FXN_GAA Arianna Tucci Str: fxn_gaa has been classified as Green List (High Evidence).
Hereditary ataxia v1.127 FXN_GAA Arianna Tucci Classified STR: FXN_GAA as Green List (high evidence)
Hereditary ataxia v1.127 FXN_GAA Arianna Tucci Str: fxn_gaa has been classified as Green List (High Evidence).
Hereditary ataxia v1.126 FXN_GAA Arianna Tucci Normal Number of Repeats for FXN_GAA was changed from 33 to 42.
Hereditary ataxia v1.125 FXN_GAA Arianna Tucci reviewed STR: FXN_GAA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Paediatric motor neuronopathies v1.16 DMPK_CTG Arianna Tucci Marked STR: DMPK_CTG as ready
Paediatric motor neuronopathies v1.16 DMPK_CTG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Paediatric motor neuronopathies v1.16 DMPK_CTG Arianna Tucci Str: dmpk_ctg has been classified as Red List (Low Evidence).
Paediatric motor neuronopathies v1.16 DMPK_CTG Arianna Tucci Classified STR: DMPK_CTG as Red List (low evidence)
Paediatric motor neuronopathies v1.16 DMPK_CTG Arianna Tucci Str: dmpk_ctg has been classified as Red List (Low Evidence).
Paediatric motor neuronopathies v1.15 DMPK_CTG Arianna Tucci edited their review of STR: DMPK_CTG: Changed rating: RED
Paediatric motor neuronopathies v1.15 DMPK_CTG Arianna Tucci Deleted their comment
Mitochondrial disorders v1.71 DMPK_CTG Arianna Tucci Marked STR: DMPK_CTG as ready
Mitochondrial disorders v1.71 DMPK_CTG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Mitochondrial disorders v1.71 DMPK_CTG Arianna Tucci Str: dmpk_ctg has been classified as Green List (High Evidence).
Mitochondrial disorders v1.71 DMPK_CTG Arianna Tucci Classified STR: DMPK_CTG as Green List (high evidence)
Mitochondrial disorders v1.71 DMPK_CTG Arianna Tucci Str: dmpk_ctg has been classified as Green List (High Evidence).
Mitochondrial disorders v1.70 DMPK_CTG Arianna Tucci STR: DMPK_CTG was added
STR: DMPK_CTG was added to Mitochondrial disorders. Sources: Expert Review
Mode of inheritance for STR: DMPK_CTG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
STR: DMPK_CTG was marked as current diagnostic
Added comment: Added to the panel following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Sources: Expert Review
Intellectual disability v2.564 DMPK_CTG Arianna Tucci Classified STR: DMPK_CTG as Green List (high evidence)
Intellectual disability v2.564 DMPK_CTG Arianna Tucci Str: dmpk_ctg has been classified as Green List (High Evidence).
Intellectual disability v2.563 DMPK_CTG Arianna Tucci Marked STR: DMPK_CTG as ready
Intellectual disability v2.563 DMPK_CTG Arianna Tucci Added comment: Comment when marking as ready: Marked as ready following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Intellectual disability v2.563 DMPK_CTG Arianna Tucci Str: dmpk_ctg has been classified as Red List (Low Evidence).
Intellectual disability v2.563 DMPK_CTG Arianna Tucci Normal Number of Repeats for DMPK_CTG was changed from 34 to 38.
Congenital muscular dystrophy v1.18 DMPK_CTG Arianna Tucci Marked STR: DMPK_CTG as ready
Congenital muscular dystrophy v1.18 DMPK_CTG Arianna Tucci Added comment: Comment when marking as ready: Marked as green following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results Sources
Congenital muscular dystrophy v1.18 DMPK_CTG Arianna Tucci Str: dmpk_ctg has been classified as Green List (High Evidence).
Skeletal Muscle Channelopathies v1.11 DMPK_CTG Arianna Tucci Deleted their comment
Congenital muscular dystrophy v1.18 DMPK_CTG Arianna Tucci Classified STR: DMPK_CTG as Green List (high evidence)
Congenital muscular dystrophy v1.18 DMPK_CTG Arianna Tucci Str: dmpk_ctg has been classified as Green List (High Evidence).
Congenital muscular dystrophy v1.17 DMPK_CTG Arianna Tucci STR: DMPK_CTG was added
STR: DMPK_CTG was added to Congenital muscular dystrophy. Sources: Expert Review
Mode of inheritance for STR: DMPK_CTG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
STR: DMPK_CTG was marked as current diagnostic
Added comment: Added to the panel following the Webex discussion with experts from the GMCs (6/09/2018) about feeding back STR results
Sources: Expert Review
Congenital myopathy v1.63 DMPK_CTG Arianna Tucci Marked STR: DMPK_CTG as ready
Congenital myopathy v1.63 DMPK_CTG Arianna Tucci Added comment: Comment when marking as ready: Marked as green following the discussion about feeding back STR results via Webexes on 6/09/2018
Congenital myopathy v1.63 DMPK_CTG Arianna Tucci Str: dmpk_ctg has been classified as Green List (High Evidence).
Congenital myopathy v1.63 DMPK_CTG Arianna Tucci Classified STR: DMPK_CTG as Green List (high evidence)
Congenital myopathy v1.63 DMPK_CTG Arianna Tucci Str: dmpk_ctg has been classified as Green List (High Evidence).
Congenital myopathy v1.62 DMPK_CTG Arianna Tucci Normal Number of Repeats for DMPK_CTG was changed from 34 to 38.
Congenital myopathy v1.61 DMPK_CTG Arianna Tucci reviewed STR: DMPK_CTG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal Muscle Channelopathies v1.11 DMPK_CTG Arianna Tucci Marked STR: DMPK_CTG as ready
Skeletal Muscle Channelopathies v1.11 DMPK_CTG Arianna Tucci Added comment: Comment when marking as ready: Marked as green following the discussion about feeding back STR results via Webexes on 6/09/2018
Skeletal Muscle Channelopathies v1.11 DMPK_CTG Arianna Tucci Str: dmpk_ctg has been classified as Green List (High Evidence).
Skeletal Muscle Channelopathies v1.11 DMPK_CTG Arianna Tucci Classified STR: DMPK_CTG as Green List (high evidence)
Skeletal Muscle Channelopathies v1.11 DMPK_CTG Arianna Tucci Str: dmpk_ctg has been classified as Green List (High Evidence).
Skeletal Muscle Channelopathies v1.10 DMPK_CTG Arianna Tucci Normal Number of Repeats for DMPK_CTG was changed from 34 to 38.
Skeletal Muscle Channelopathies v1.9 DMPK_CTG Arianna Tucci reviewed STR: DMPK_CTG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None; Current diagnostic: yes
Congenital disorders of glycosylation v1.20 CAD Konstantinos Varvagiannis reviewed gene: CAD: Rating: AMBER; Mode of pathogenicity: None; Publications: 28007989; Phenotypes: Epileptic encephalopathy, early infantile, 50 - MIM 616457; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1365 SIX3 Sarah Leigh Added comment: Comment on phenotypes: Schizencephaly 269160
Early onset or syndromic epilepsy v0.1365 SIX3 Sarah Leigh Phenotypes for gene: SIX3 were changed from Holoprosencephaly 2 157170 to Holoprosencephaly 2 157170; Schizencephaly 269160
Congenital disorders of glycosylation v1.20 CAD Konstantinos Varvagiannis Deleted their review
Congenital disorders of glycosylation v1.20 CAD Konstantinos Varvagiannis reviewed gene: CAD: Rating: AMBER; Mode of pathogenicity: None; Publications: 28007989; Phenotypes: Epileptic encephalopathy, early infantile, 50 - MIM 616457; Mode of inheritance: None
Limb disorders v0.350 DVL1 Eleanor Williams Publications for gene: DVL1 were set to 25817016
Limb disorders v0.349 DVL1 Eleanor Williams Publications for gene: DVL1 were set to
Limb disorders v0.348 DVL1 Eleanor Williams Added comment: Comment on mode of pathogenicity: PMID:25817016 suggests known variants causing Robinow syndrome are gain of function
Limb disorders v0.348 DVL1 Eleanor Williams Mode of pathogenicity for gene: DVL1 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Early onset or syndromic epilepsy v0.1364 NAGA Louise Daugherty Added comment: Comment on mode of inheritance: Added MOI from external clinical review and publications
Early onset or syndromic epilepsy v0.1364 NAGA Louise Daugherty Mode of inheritance for gene: NAGA was changed from to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v2.562 CAD Konstantinos Varvagiannis gene: CAD was added
gene: CAD was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: CAD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAD were set to 25678555; 28007989
Phenotypes for gene: CAD were set to Epileptic encephalopathy, early infantile, 50 - MIM 616457
Penetrance for gene: CAD were set to Complete
Review for gene: CAD was set to AMBER
gene: CAD was marked as current diagnostic
Added comment: Biallelic pathogenic variants in CAD cause Epileptic encephalopathy, early infantile, 50 - MIM 616457.

Overall 5 individuals from 4 unrelated families have been reported in detail in PMIDs 25678555 and 28007989 (table 1 in this article provides a summary).

The phenotype consisted of developmental delay which preceded the onset of seizures (6 months to 2 years) and hematologic anomalies (anemia and anisopoikilocytosis). The patients presented developmental stagnation/regression, which in most cases occurred several months following the seizure onset.

CAD is a tri-functional protein catalyzing the first 3 steps of the de novo pyrimidine biosynthesis.

In total, 5 variants have been reported (2 missense, 1 nonsense and 2 splice-site SNVs) with functional studies (cDNA, metabolites) supporting pathogenicity and disruption of this pathway.

CAD mutations have previously been studied in other model organisms.

Mutations in enzymes catalyzing downstream steps of the same pathway are associated with other syndromes.

The disorder appears to be amenable to dietary intervention (uridine supplementation).

CAD is included in gene panels for intellectual disability offered by different diagnostic laboratories.

As a result, this gene can be considered for inclusion in the ID panel as amber or green.
Sources: Literature
Early onset or syndromic epilepsy v0.1363 SDHA Sarah Leigh Marked gene: SDHA as ready
Early onset or syndromic epilepsy v0.1363 SDHA Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least four variants reported in two unrelated cases, one of autosomal recessive encephalomyopathy and isolated mitochondrial complex II deficiency and the other of Leigh syndrome. Seizures do not appear to be a common feature of either phenotype as there are numerous reports of biallelic SDHA variants in cases with out seizures (PMIDs: 22972948, 16798039,12794685, 10746566 & 7550341).
Early onset or syndromic epilepsy v0.1363 SDHA Sarah Leigh Gene: sdha has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1363 NAGA Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Early onset or syndromic epilepsy v0.1363 NAGA Louise Daugherty Phenotypes for gene: NAGA were changed from to Schindler disease, type I, 609241; seizures
Early onset or syndromic epilepsy v0.1362 CAD Konstantinos Varvagiannis gene: CAD was added
gene: CAD was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: CAD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CAD were set to 25678555; 28007989
Phenotypes for gene: CAD were set to Epileptic encephalopathy, early infantile, 50 - MIM 616457
Penetrance for gene: CAD were set to Complete
Review for gene: CAD was set to GREEN
Added comment: Biallelic pathogenic variants in CAD cause Epileptic encephalopathy, early infantile, 50 - MIM 616457.

Overall 5 individuals from 4 unrelated families have been reported in detail in PMIDs 25678555 and 28007989 (table 1 in this article provides a summary).

The phenotype consisted of developmental delay which preceded the onset of seizures (6 months to 2 years) and hematologic anomalies (anemia and anisopoikilocytosis). The patients presented developmental stagnation/regression, which in most cases occurred several months following the seizure onset.

CAD is a tri-functional protein catalyzing the first 3 steps of the de novo pyrimidine biosynthesis.

In total, 5 variants have been reported (2 missense, 1 nonsense and 2 splice-site SNVs) with functional studies (cDNA, metabolites) supporting pathogenicity and disruption of this pathway.

CAD mutations have previously been studied in other model organisms.

Mutations in enzymes catalyzing downstream steps of the same pathway are associated with other syndromes.

The disorder appears to be amenable to dietary intervention (uridine supplementation).

As a result, this gene can be considered for inclusion in the epilepsy panel as green (or amber).
Sources: Literature
Limb disorders v0.347 BHLHA9 Eleanor Williams Mode of inheritance for gene: BHLHA9 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1362 SDHA Sarah Leigh Added comment: Comment on publications: PMIDs: 22972948, 16798039,12794685, 10746566 & 7550341 report biallelic variants, but no seizures.
Early onset or syndromic epilepsy v0.1362 SDHA Sarah Leigh Publications for gene: SDHA were set to
Hereditary spastic paraplegia v1.72 ERLIN1 Rebecca Foulger Publications for gene: ERLIN1 were set to PMID: 24482476
Limb disorders v0.346 WNT5A Eleanor Williams Added comment: Comment on mode of inheritance: Changed to imprinted status unknown as reviewer had selected this.
Limb disorders v0.346 WNT5A Eleanor Williams Mode of inheritance for gene: WNT5A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v0.345 TRPS1 Eleanor Williams Added comment: Comment on mode of inheritance: Changed to imprinted status unknown as reviewer had selected this.
Limb disorders v0.345 TRPS1 Eleanor Williams Mode of inheritance for gene: TRPS1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v0.344 TP63 Eleanor Williams Added comment: Comment on mode of inheritance: Changed to imprinted status unknown as reviewer had selected this.
Limb disorders v0.344 TP63 Eleanor Williams Mode of inheritance for gene: TP63 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v0.1361 MTR Louise Daugherty Classified gene: MTR as Green List (high evidence)
Early onset or syndromic epilepsy v0.1361 MTR Louise Daugherty Gene: mtr has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1360 MTR Louise Daugherty Publications for gene: MTR were set to 9453374; 12068375; 9683607; 28666289
Limb disorders v0.343 ABL1 Rebecca Foulger Added comment: Comment on mode of pathogenicity: Both variants reported so far in PMID:28288113 are missense.
Limb disorders v0.343 ABL1 Rebecca Foulger Mode of pathogenicity for gene: ABL1 was changed from None to Other
Limb disorders v0.342 ABL1 Rebecca Foulger Classified gene: ABL1 as Green List (high evidence)
Limb disorders v0.342 ABL1 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Green: ABL1 was originally added to the TAAD panel by the external reviewer Chris Buxton. The phenotypes reported in PMID:28288113 are appropriate for inclusion on the limb panel (including clinodactyly, arachnodactyly, camptodactylyly) and seen in sufficient cases (>3 families, 2 missense variants) for a diagnostic rating.
Limb disorders v0.342 ABL1 Rebecca Foulger Gene: abl1 has been classified as Green List (High Evidence).
Limb disorders v0.341 ABL1 Rebecca Foulger commented on gene: ABL1: Digit anomalies were seen in all four families from PMID:28288113: Subject 1 (family 1) had a hindfoot deformity. Subject 2 (family 1) had long fingers and toes. Subject 3 (family 2), had 5th finger clinodactyly bilaterally. Subject 4 (family 3) had clinodactyly of the 5th fingers. Subject 5 (family 3) had arachnodactyly (Spider hands), Subject 6 (family 4) had bilateral camptodactylyly of little fingers and bilateral 2-3 toe syndactyly.
Limb disorders v0.341 ABL1 Rebecca Foulger gene: ABL1 was added
gene: ABL1 was added to Limb disorders. Sources: Literature
Mode of inheritance for gene: ABL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ABL1 were set to 28288113
Phenotypes for gene: ABL1 were set to congential heart disease, skeletal abnormalities and failure to thrive; clinodactyly; syndactyly; arachnodactyly
Added comment: Wang et al.,2017 (PMID:28288113) report ABL1 germline variants cosegregating with an autosomal dominant disorder characterized by congenital heart disease, skeletal abnormalities and failure to thrive. The variant c.734A>G (p.Tyr245Cys) was found to occur de novo in 3 individuals (families 1-2) and in family 3, the variant was seen in the affected father and daughter. Additionally, a de novo c.1066G>A (p.Ala356Thr) variant was identified in a sixth individual (family 4). Functional assays show that both missense variants cause increased phosphorylation, suggesting increased ABL1 kinase activity.
Sources: Literature
Limb disorders v0.340 TBX4 Eleanor Williams Added comment: Comment on mode of inheritance: Changing to imprinted status unknown as per the reviewer selection.
Limb disorders v0.340 TBX4 Eleanor Williams Mode of inheritance for gene: TBX4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hypertrophic cardiomyopathy v1.23 MT-TL1 Ellen McDonagh gene: MT-TL1 was added
gene: MT-TL1 was added to Hypertrophic cardiomyopathy - teen and adult. Sources: Expert Review
Mode of inheritance for gene gene: MT-TL1 was set to MITOCHONDRIAL
Added comment: This gene was suggested by Dr Atsuko Okazaki (Division of Genomic Medicine Research, Medical Genomics Center, National Center for Global Health and Medicine, Tokyo, Japan) to be added to this panel. Comments from Dr Atsuko Okazaki: "Among our ~2000 patients, certain numbers of hypertrophic cardiomyopathy patients have m.3243A>G mutation in MT-TL1 with high heteroplasty rate in the heart. Although reporting mitochondrial DNA mutations with their pathogenicity is always challenging due to the heteroplasty rate in affected organs, I think it might be one possibility to let clinicians know that m.3243A>G is a causative mutation for hypertrophic cardiomyopathy if mutation rate is high in the heart."
Sources: Expert Review
Early onset or syndromic epilepsy v0.1359 MTR Louise Daugherty Publications for gene: MTR were set to 12068375; 9683607; 28666289
Mitochondrial disorders v1.69 MT-ATP8 Ellen McDonagh commented on gene: MT-ATP8: Comments from Dr Atsuko Okazaki (Division of Genomic Medicine Research, Medical Genomics Center, National Center for Global Health and Medicine, Tokyo, Japan): "Only m.8528T>C (to be exact, it is an overlapping region of MT-ATP6/ATP8) can be reported as a confirmed mutation for infantile hypertrophic cardiomyopathy. In comparison, m.8527A>G is a polymorphism for MT-ATP8 and possibly disease-associated for MT-ATP6 (amber/red) although both m.8527A>G and m.8528T>C are located in MT-ATP8 gene."
Early onset or syndromic epilepsy v0.1358 MTR Louise Daugherty Classified gene: MTR as Amber List (moderate evidence)
Early onset or syndromic epilepsy v0.1358 MTR Louise Daugherty Added comment: Comment on list classification: Not enough evidence to date to rate this gene green, kept this gene Amber on this panel until further evidence.
Early onset or syndromic epilepsy v0.1358 MTR Louise Daugherty Gene: mtr has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1357 MTR Louise Daugherty Added comment: Comment on publications: added publication to support gene-disease association
Early onset or syndromic epilepsy v0.1357 MTR Louise Daugherty Publications for gene: MTR were set to
Early onset or syndromic epilepsy v0.1356 MTHFR Louise Daugherty Publications for gene: MTHFR were set to 29391032; 21778025; 12406076; 12840091; 9587029; 30267335; 24556013
Hypophosphataemia or rickets v0.24 FAM20C Ivone Leong Classified gene: FAM20C as Green List (high evidence)
Hypophosphataemia or rickets v0.24 FAM20C Ivone Leong Added comment: Comment on list classification: Promoted from red to green based on previous comment.
Hypophosphataemia or rickets v0.24 FAM20C Ivone Leong Gene: fam20c has been classified as Green List (High Evidence).
Hypophosphataemia or rickets v0.23 FAM20C Ivone Leong Publications for gene: FAM20C were set to
Hypophosphataemia or rickets v0.22 CYP2R1 Ivone Leong Classified gene: CYP2R1 as Green List (high evidence)
Hypophosphataemia or rickets v0.22 CYP2R1 Ivone Leong Added comment: Comment on list classification: Promoted from red to green based on previous comment. CYP2R1 is also confirmed as associated with Rickets due to defect in vitamin D 25-hydroxylation on OMIM but no phenotypes are listed for it on Gene2Phenotype.
Hypophosphataemia or rickets v0.22 CYP2R1 Ivone Leong Gene: cyp2r1 has been classified as Green List (High Evidence).
Hypophosphataemia or rickets v0.21 CYP2R1 Ivone Leong Publications for gene: CYP2R1 were set to
Hypophosphataemia or rickets v0.20 CLCN5 Ivone Leong Classified gene: CLCN5 as Amber List (moderate evidence)
Hypophosphataemia or rickets v0.20 CLCN5 Ivone Leong Added comment: Comment on list classification: Promoted from red to amber based on the previous comment. CLCN5 is confirmed to be associated with hypophosphataemic rickets on OMIM, but no phenotypes are listed for it on Gene2Phenotype. It is also a green gene on the Skeletal dysplasia panel (Version 1.129).
Hypophosphataemia or rickets v0.20 CLCN5 Ivone Leong Gene: clcn5 has been classified as Amber List (Moderate Evidence).
Hypophosphataemia or rickets v0.19 CLCN5 Ivone Leong Publications for gene: CLCN5 were set to
Hypophosphataemia or rickets v0.18 VDR Ivone Leong Classified gene: VDR as Green List (high evidence)
Hypophosphataemia or rickets v0.18 VDR Ivone Leong Added comment: Comment on list classification: Promoted from amber to green based on previous comment.
Hypophosphataemia or rickets v0.18 VDR Ivone Leong Gene: vdr has been classified as Green List (High Evidence).
Hypophosphataemia or rickets v0.17 CYP27B1 Ivone Leong Classified gene: CYP27B1 as Green List (high evidence)
Hypophosphataemia or rickets v0.17 CYP27B1 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green based on previous comments.
Hypophosphataemia or rickets v0.17 CYP27B1 Ivone Leong Gene: cyp27b1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1355 SDHA Sarah Leigh Added comment: Comment on phenotypes: Mitochondrial respiratory chain complex II deficiency 252011
Early onset or syndromic epilepsy v0.1355 SDHA Sarah Leigh Phenotypes for gene: SDHA were changed from to Leigh syndrome 256000; Mitochondrial respiratory chain complex II deficiency 252011
Hypophosphataemia or rickets v0.16 CYP27B1 Ivone Leong Publications for gene: CYP27B1 were set to
Hypophosphataemia or rickets v0.15 SLC9A3R1 Ivone Leong Classified gene: SLC9A3R1 as Amber List (moderate evidence)
Hypophosphataemia or rickets v0.15 SLC9A3R1 Ivone Leong Added comment: Comment on list classification: Promoted from red to amber based on previous comment.
Hypophosphataemia or rickets v0.15 SLC9A3R1 Ivone Leong Gene: slc9a3r1 has been classified as Amber List (Moderate Evidence).
Hypophosphataemia or rickets v0.14 SLC9A3R1 Ivone Leong Publications for gene: SLC9A3R1 were set to
Early onset or syndromic epilepsy v0.1354 SDHA Sarah Leigh Mode of inheritance for gene: SDHA was changed from to BIALLELIC, autosomal or pseudoautosomal
Hypophosphataemia or rickets v0.13 FGFR1 Ivone Leong Classified gene: FGFR1 as Green List (high evidence)
Hypophosphataemia or rickets v0.13 FGFR1 Ivone Leong Added comment: Comment on list classification: Promoted from red to green based on the previous comment.
Hypophosphataemia or rickets v0.13 FGFR1 Ivone Leong Gene: fgfr1 has been classified as Green List (High Evidence).
Hypophosphataemia or rickets v0.12 FGFR1 Ivone Leong Publications for gene: FGFR1 were set to
Hypophosphataemia or rickets v0.11 SLC34A1 Ivone Leong Publications for gene: SLC34A1 were set to
Hypophosphataemia or rickets v0.10 SLC34A1 Ivone Leong Classified gene: SLC34A1 as Green List (high evidence)
Hypophosphataemia or rickets v0.10 SLC34A1 Ivone Leong Added comment: Comment on list classification: Promoted from red to green based on previous comments.
Hypophosphataemia or rickets v0.10 SLC34A1 Ivone Leong Gene: slc34a1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1353 SEPSECS Sarah Leigh Marked gene: SEPSECS as ready
Early onset or syndromic epilepsy v0.1353 SEPSECS Sarah Leigh Added comment: Comment when marking as ready: Associated with phenotype in OMIM and not in Gen2Phen. At least three variants identified in unrelated cases of Pontocerebellar hypoplasia type 2D 613811, however, the majority of published cases of this condition do not include seizures.
Early onset or syndromic epilepsy v0.1353 SEPSECS Sarah Leigh Gene: sepsecs has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1353 SEPSECS Sarah Leigh Classified gene: SEPSECS as Green List (high evidence)
Early onset or syndromic epilepsy v0.1353 SEPSECS Sarah Leigh Gene: sepsecs has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1352 SEPSECS Sarah Leigh Publications for gene: SEPSECS were set to 20920667; 25044680
Early onset or syndromic epilepsy v0.1351 SEPSECS Sarah Leigh Deleted their comment
Early onset or syndromic epilepsy v0.1351 SEPSECS Sarah Leigh Added comment: Comment on publications: No seizures reported in two milder cases of Pontocerebellar hypoplasia type 2D 613811 in PMID: 26888482. SEPSECS variants not reported in the cases that have seizures (21 trios) in PMID: 25590979. PMID: 26805434 case report of pontocerebellar hypoplasia type 2D and optic nerve atrophy, with homozygous SEPSECS variannt, but no seizures.
Early onset or syndromic epilepsy v0.1351 SEPSECS Sarah Leigh Publications for gene: SEPSECS were set to 20920667; 25044680
Rare multisystem ciliopathy disorders v1.79 LZTFL1 Eleanor Williams Publications for gene: LZTFL1 were set to PMID: 22510444; 23692385
Rare multisystem ciliopathy disorders v1.78 LZTFL1 Eleanor Williams commented on gene: LZTFL1
Limb disorders v0.339 WDR60 Eleanor Williams Publications for gene: WDR60 were set to
Limb disorders v0.338 LBR Eleanor Williams Publications for gene: LBR were set to 18382993; 12618959; 21327084; 12118250
Limb disorders v0.337 LBR Eleanor Williams commented on gene: LBR
Limb disorders v0.337 WDR60 Eleanor Williams commented on gene: WDR60
Limb disorders v0.337 ZIC3 Eleanor Williams commented on gene: ZIC3
Unexplained kidney failure in young people v1.20 ANOS1 Anna de Burca reviewed gene: ANOS1: Rating: RED; Mode of pathogenicity: None; Publications: 11531922, 9719154; Phenotypes: Hypogonadotropic hypogonadism 1 with or without anosmia (Kallmann syndrome 1); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early onset or syndromic epilepsy v0.1350 MTR Louise Daugherty Phenotypes for gene: MTR were changed from Homocystinuria-megaloblastic anemia, cblG complementation type, 250940; seizures to Homocystinuria-megaloblastic anemia, cblG complementation type, 250940; methionine synthase deficiency type cblG; seizures
Early onset or syndromic epilepsy v0.1349 MTR Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Early onset or syndromic epilepsy v0.1349 MTR Louise Daugherty Phenotypes for gene: MTR were changed from to Homocystinuria-megaloblastic anemia, cblG complementation type, 250940; seizures
Early onset or syndromic epilepsy v0.1348 MTR Louise Daugherty Mode of inheritance for gene: MTR was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1347 SEPSECS Sarah Leigh Added comment: Comment on publications: No seizures reported in two milder cases of Pontocerebellar hypoplasia type 2D 613811 in PMID: 26888482.
Early onset or syndromic epilepsy v0.1347 SEPSECS Sarah Leigh Publications for gene: SEPSECS were set to 20920667; 25044680
Early onset or syndromic epilepsy v0.1346 SEPSECS Sarah Leigh Mode of inheritance for gene: SEPSECS was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1345 SEPSECS Sarah Leigh Mode of inheritance for gene: SEPSECS was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1344 SEPSECS Sarah Leigh Publications for gene: SEPSECS were set to
Early onset or syndromic epilepsy v0.1343 SEPSECS Sarah Leigh Phenotypes for gene: SEPSECS were changed from to Pontocerebellar hypoplasia type 2D 613811
Early onset or syndromic epilepsy v0.1342 SETBP1 Sarah Leigh Marked gene: SETBP1 as ready
Early onset or syndromic epilepsy v0.1342 SETBP1 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least five variants reported in twelve unrelated cases in which seizures are a phenotypic feature.
Early onset or syndromic epilepsy v0.1342 SETBP1 Sarah Leigh Gene: setbp1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1342 SETBP1 Sarah Leigh Classified gene: SETBP1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1342 SETBP1 Sarah Leigh Gene: setbp1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1341 SETBP1 Sarah Leigh Publications for gene: SETBP1 were set to
Early onset or syndromic epilepsy v0.1340 SETBP1 Sarah Leigh Mode of inheritance for gene: SETBP1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v0.1339 SETBP1 Sarah Leigh Phenotypes for gene: SETBP1 were changed from to Schinzel-Giedion midface retraction syndrome 269150
Early onset or syndromic epilepsy v0.1338 SIX3 Sarah Leigh Phenotypes for gene: SIX3 were changed from to Holoprosencephaly 2 157170
Early onset or syndromic epilepsy v0.1337 SIX3 Sarah Leigh Mode of inheritance for gene: SIX3 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v0.1336 SLC25A12 Sarah Leigh Marked gene: SLC25A12 as ready
Early onset or syndromic epilepsy v0.1336 SLC25A12 Sarah Leigh Added comment: Comment when marking as ready: Associated with phenotype in OMIM and not in Gen2Phen. At least three homozygous variants identified in unrelated cases in which seizures are a phenotypic feature.
Early onset or syndromic epilepsy v0.1336 SLC25A12 Sarah Leigh Gene: slc25a12 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1336 SLC25A12 Sarah Leigh Classified gene: SLC25A12 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1336 SLC25A12 Sarah Leigh Gene: slc25a12 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1335 SLC25A12 Sarah Leigh Added comment: Comment on publications: Homozygous missense variants: c.1058G>A; p.Arg353Gln, segregated with disease in this kindred in a child with epilepsy (PMID 24515575);
c.1769A>G, p.Gln590Arg in a 3 year old girl (PMID: 19641205); de novo in an infant c.1335C>A, p.Asn445Lys (PMID 27290639).
Early onset or syndromic epilepsy v0.1335 SLC25A12 Sarah Leigh Publications for gene: SLC25A12 were set to 24515575; 19641205; 27290639
Early onset or syndromic epilepsy v0.1334 SLC25A12 Sarah Leigh Publications for gene: SLC25A12 were set to
Early onset or syndromic epilepsy v0.1333 SLC25A12 Sarah Leigh Phenotypes for gene: SLC25A12 were changed from to Epileptic encephalopathy, early infantile, 39 612949
Early onset or syndromic epilepsy v0.1332 SLC25A12 Sarah Leigh Mode of inheritance for gene: SLC25A12 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1331 SLC6A8 Sarah Leigh Classified gene: SLC6A8 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1331 SLC6A8 Sarah Leigh Gene: slc6a8 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1330 SLC6A8 Sarah Leigh Marked gene: SLC6A8 as ready
Early onset or syndromic epilepsy v0.1330 SLC6A8 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least four variants reported
in at least four unrelated male cases in which seizures are a phenotypic feature.
Early onset or syndromic epilepsy v0.1330 SLC6A8 Sarah Leigh Gene: slc6a8 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1330 SLC6A8 Sarah Leigh Publications for gene: SLC6A8 were set to
Early onset or syndromic epilepsy v0.1329 SLC6A8 Sarah Leigh Phenotypes for gene: SLC6A8 were changed from to Cerebral creatine deficiency syndrome 1 300352
Early onset or syndromic epilepsy v0.1328 SLC6A8 Sarah Leigh Mode of inheritance for gene: SLC6A8 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early onset or syndromic epilepsy v0.1327 SNORD118 Sarah Leigh Marked gene: SNORD118 as ready
Early onset or syndromic epilepsy v0.1327 SNORD118 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and in Gen2Phen gene (Plausible disease-causing mutations within, affecting or encompassing the coding region of a single gene identified in multiple (>3) unrelated cases/families with both the relevant disease (RD) and an incidental disorder). At least 13 variants reported in 13 cases in which seizures are a phenotypic feature.
Early onset or syndromic epilepsy v0.1327 SNORD118 Sarah Leigh Gene: snord118 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1327 SNORD118 Sarah Leigh Mode of inheritance for gene: SNORD118 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1326 SNORD118 Sarah Leigh Classified gene: SNORD118 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1326 SNORD118 Sarah Leigh Gene: snord118 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1325 SNORD118 Sarah Leigh Publications for gene: SNORD118 were set to
Early onset or syndromic epilepsy v0.1324 DOLK Konstantinos Varvagiannis reviewed gene: DOLK: Rating: AMBER; Mode of pathogenicity: None; Publications: 24144945, 28816422; Phenotypes: ; Mode of inheritance: None
Early onset or syndromic epilepsy v0.1324 SNORD118 Sarah Leigh Phenotypes for gene: SNORD118 were changed from to Leukoencephalopathy, brain calcifications, and cysts 614561
Thoracic aortic aneurysm or dissection v1.78 ABL1 Rebecca Foulger Mode of inheritance for gene: ABL1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v0.1323 MTHFR Louise Daugherty Classified gene: MTHFR as Green List (high evidence)
Early onset or syndromic epilepsy v0.1323 MTHFR Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association
Early onset or syndromic epilepsy v0.1323 MTHFR Louise Daugherty Gene: mthfr has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1322 MTHFR Louise Daugherty Added comment: Comment on publications: Added publications to support upgrading of the gene to Green
Early onset or syndromic epilepsy v0.1322 MTHFR Louise Daugherty Publications for gene: MTHFR were set to
Early onset or syndromic epilepsy v0.1321 EIF2B3 Rebecca Foulger Marked gene: EIF2B3 as ready
Early onset or syndromic epilepsy v0.1321 EIF2B3 Rebecca Foulger Gene: eif2b3 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1321 EIF2B1 Rebecca Foulger Marked gene: EIF2B1 as ready
Early onset or syndromic epilepsy v0.1321 EIF2B1 Rebecca Foulger Gene: eif2b1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1321 ETHE1 Rebecca Foulger Marked gene: ETHE1 as ready
Early onset or syndromic epilepsy v0.1321 ETHE1 Rebecca Foulger Gene: ethe1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1321 DNM1L Rebecca Foulger Added comment: Comment on mode of inheritance: Both autosomal dominant and autosomal recessive inheritance reported by OMIM for 'Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1, 614388'.
Early onset or syndromic epilepsy v0.1321 DNM1L Rebecca Foulger Mode of inheritance for gene: DNM1L was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1320 MMACHC Rebecca Foulger Marked gene: MMACHC as ready
Early onset or syndromic epilepsy v0.1320 MMACHC Rebecca Foulger Gene: mmachc has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1320 MPDU1 Rebecca Foulger Marked gene: MPDU1 as ready
Early onset or syndromic epilepsy v0.1320 MPDU1 Rebecca Foulger Gene: mpdu1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1320 MPDU1 Rebecca Foulger Classified gene: MPDU1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1320 MPDU1 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Green review by Zornitza plus sufficient (>3) cases of seizures in CDG patients with MPDU1 variants from PMIDs:11733556, 11733564 and 28122681.
Early onset or syndromic epilepsy v0.1320 MPDU1 Rebecca Foulger Gene: mpdu1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1319 MPDU1 Rebecca Foulger Publications for gene: MPDU1 were set to
Early onset or syndromic epilepsy v0.1318 MPDU1 Rebecca Foulger commented on gene: MPDU1: PMID:28122681 (Al Teneiji et al. 2017) report 15 patients, 1 of which had MPDU1-CDG. The patient had a homozygous c.218G>A (p.G73E) variant in MPDU1, and seizures were reported amongst the phenotypes (Table 2).
Early onset or syndromic epilepsy v0.1318 MTHFR Louise Daugherty Added comment: Comment on mode of inheritance: Added MOI from external clinical review and publications
Early onset or syndromic epilepsy v0.1318 MTHFR Louise Daugherty Mode of inheritance for gene: MTHFR was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1317 MTHFR Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Early onset or syndromic epilepsy v0.1317 MTHFR Louise Daugherty Phenotypes for gene: MTHFR were changed from to Homocystinuria due to MTHFR deficiency, 236250; seizures
Early onset or syndromic epilepsy v0.1316 MPDU1 Rebecca Foulger commented on gene: MPDU1: Schenk et al 2001 (PMID:11733564) report 3 unrelated patients with congenital disorder of glycosylation CDG-If, and variants in MPDU1. Patient S had severed intractable seizures from birth, which worsened up to his death age 10 months. Patient A had generalized seizures from age 15 months that responded well to valproate (listed as generalized febrile seizures in Table 1). Patient L had hypertonic attacks in infancy.
Early onset or syndromic epilepsy v0.1316 MPDU1 Rebecca Foulger commented on gene: MPDU1
Hypophosphataemia or rickets v0.9 SLC9A3R1 Ivone Leong reviewed gene: SLC9A3R1: Rating: AMBER; Mode of pathogenicity: None; Publications: 18784102, 25296721, 19073985; Phenotypes: ; Mode of inheritance: None
Early onset or syndromic epilepsy v0.1316 MPDU1 Rebecca Foulger Mode of inheritance for gene: MPDU1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1315 MPDU1 Rebecca Foulger Phenotypes for gene: MPDU1 were changed from to Congenital disorder of glycosylation, type If, 609180
Early onset or syndromic epilepsy v0.1314 MMADHC Rebecca Foulger Marked gene: MMADHC as ready
Early onset or syndromic epilepsy v0.1314 MMADHC Rebecca Foulger Gene: mmadhc has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1314 MMADHC Rebecca Foulger Classified gene: MMADHC as Green List (high evidence)
Early onset or syndromic epilepsy v0.1314 MMADHC Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green. Green rating by Zornitza, and sufficient unrelated cases of patients with MMADHC variants and seizures (4 cases in PMID:18385497) for inclusion on panel.
Early onset or syndromic epilepsy v0.1314 MMADHC Rebecca Foulger Gene: mmadhc has been classified as Green List (High Evidence).
Brain channelopathy v1.33 SPR Sarah Leigh Classified gene: SPR as Green List (high evidence)
Brain channelopathy v1.33 SPR Sarah Leigh Added comment: Comment on list classification: Recommedation from Arianna Tucci to add SPR to this panel
Brain channelopathy v1.33 SPR Sarah Leigh Gene: spr has been classified as Green List (High Evidence).
Brain channelopathy v1.32 SPR Sarah Leigh gene: SPR was added
gene: SPR was added to Brain channelopathy. Sources: Literature
Mode of inheritance for gene: SPR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: SPR were set to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency 612716
Review for gene: SPR was set to GREEN
Added comment: According to the recommendations of Arianna Tucci (Genomics England Clinical Fellow), the phenotypes associated with variants in SPR are not associated with epileptic seizures, rather with myoclonic movements as reported in the following publications: PMID 16650784: myoclonic jerks sometimes observed; PMID 21431957: myoclonic movements of hands and face; PMID 28189489 sudden stiffening of the whole body, extension of all extremities, and upward gaze lasting for several minutes often after meals in a 3 month old boy (including during a hospital stay), initially, mistaken for seizures, however 24h video-EEG showed no epileptiform discharges or any EEG correlate. Therefore this phenotype is relevant to the Brain channelopathy panel.
Sources: Literature
Early onset or syndromic epilepsy v0.1313 MMADHC Rebecca Foulger commented on gene: MMADHC
Early onset or syndromic epilepsy v0.1313 MMADHC Rebecca Foulger Mode of inheritance for gene: MMADHC was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1312 SPR Sarah Leigh Marked gene: SPR as ready
Early onset or syndromic epilepsy v0.1312 SPR Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene, however, the associated seizures appear to have been misdiagnosed and are infact myoclonic movements (PMIDs 16650784;21431957;28189489).
Early onset or syndromic epilepsy v0.1312 SPR Sarah Leigh Gene: spr has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1312 SPR Sarah Leigh Publications for gene: SPR were set to
Early onset or syndromic epilepsy v0.1311 SPR Sarah Leigh reviewed gene: SPR: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Early onset or syndromic epilepsy v0.1311 MMADHC Rebecca Foulger Phenotypes for gene: MMADHC were changed from to Methylmalonic aciduria and homocystinuria, cblD type, 277410
Early onset or syndromic epilepsy v0.1310 EXOSC3 Rebecca Foulger Publications for gene: EXOSC3 were set to 25144110; 25149867; 23975261
Early onset or syndromic epilepsy v0.1309 MMACHC Rebecca Foulger Publications for gene: MMACHC were set to
Early onset or syndromic epilepsy v0.1308 MMACHC Rebecca Foulger Marked gene: MMACHC as ready
Early onset or syndromic epilepsy v0.1308 MMACHC Rebecca Foulger Gene: mmachc has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1308 MMACHC Rebecca Foulger Classified gene: MMACHC as Green List (high evidence)
Early onset or syndromic epilepsy v0.1308 MMACHC Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Green review by Zornitza plus sufficient (>3) cases of cblC disease patients with MMACHC variants and seizures from PMIDs 17431913 and 20924684).
Early onset or syndromic epilepsy v0.1308 MMACHC Rebecca Foulger Gene: mmachc has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1307 MMACHC Rebecca Foulger commented on gene: MMACHC: PMID:20924684 (Wang et al, 2010) report 43 patients with combined methylmalonic acidemia and hyperhomocysteinemia (cblC type), 50% of which presented with seizures. Homozygous MMACHC variants are listed in Table 4.
Early onset or syndromic epilepsy v0.1307 SPR Sarah Leigh Mode of inheritance for gene: SPR was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1306 DBT Rebecca Foulger Marked gene: DBT as ready
Early onset or syndromic epilepsy v0.1306 DBT Rebecca Foulger Gene: dbt has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1306 DBT Rebecca Foulger Classified gene: DBT as Amber List (moderate evidence)
Early onset or syndromic epilepsy v0.1306 DBT Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber: DBT encodes the E2 subunit of the BCKD complex. The other complex subunits (BCKDHA and BCKDHB) are Green on this panel, and all 3 genes are associated with Maple syrup urine disease (MSUD, MIM:248600). Seizures are a recognised symptom of MSUD, and although there is generalized information about DBT causing intermediate forms of the disease with later-onset seizures, specific cases with DBT variants are required before promoting to Green.
Early onset or syndromic epilepsy v0.1306 DBT Rebecca Foulger Gene: dbt has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1305 DBT Rebecca Foulger Tag watchlist tag was added to gene: DBT.
Early onset or syndromic epilepsy v0.1305 EIF2B1 Rebecca Foulger Classified gene: EIF2B1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v0.1305 EIF2B1 Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber after discussion in Genomics England Curation team. Although other EIF2B subunits are also associated with Vanishing white matter (VWM) and rated Green on the panel, there are currently insufficient clinical/literature cases of patients with EIF2B1 and seizures (2 patients in PMIDs 25761052 and 25843247). Therefore added 'watchlist' tag while awaiting further cases.
Early onset or syndromic epilepsy v0.1305 EIF2B1 Rebecca Foulger Gene: eif2b1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1304 EIF2B3 Rebecca Foulger Marked gene: EIF2B3 as ready
Early onset or syndromic epilepsy v0.1304 EIF2B3 Rebecca Foulger Gene: eif2b3 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1304 EIF2B3 Rebecca Foulger Tag watchlist tag was added to gene: EIF2B3.
Early onset or syndromic epilepsy v0.1304 EIF2B1 Rebecca Foulger Tag watchlist tag was added to gene: EIF2B1.
Early onset or syndromic epilepsy v0.1304 EIF2B3 Rebecca Foulger Classified gene: EIF2B3 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v0.1304 EIF2B3 Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber after discussion in Genomics England Curation team. Although other EIF2B subunits are also associated with Vanishing white matter (VWM) and rated Green on the panel, there are currently insufficient clinical/literature cases of patients with EIF2B3 and seizures (1 patient in 19158808). Therefore added 'watchlist' tag while awaiting further cases.
Early onset or syndromic epilepsy v0.1304 EIF2B3 Rebecca Foulger Gene: eif2b3 has been classified as Amber List (Moderate Evidence).
Cerebellar hypoplasia v1.25 COASY Louise Daugherty Classified gene: COASY as Amber List (moderate evidence)
Cerebellar hypoplasia v1.25 COASY Louise Daugherty Added comment: Comment on list classification: New gene. Rated Amber until more cases on gene and disease association are reported.
Cerebellar hypoplasia v1.25 COASY Louise Daugherty Gene: coasy has been classified as Amber List (Moderate Evidence).
Cerebellar hypoplasia v1.24 COASY Louise Daugherty commented on gene: COASY: added watchlist tag
Cerebellar hypoplasia v1.24 COASY Louise Daugherty gene: COASY was added
gene: COASY was added to Cerebellar hypoplasia. Sources: Literature
watchlist tags were added to gene: COASY.
Mode of inheritance for gene: COASY was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COASY were set to 30089828; 24360804
Phenotypes for gene: COASY were set to Severe prenatal onset pontocerebellar hypoplasia, microcephaly, arthrogryposis
Review for gene: COASY was set to AMBER
Added comment: From Dijk et al. (2018) PMID: 30089828 variants in the gene Coenzyme A (CoA) synthase (COASY) gene, an enzyme essential in CoA synthesis. A single variant was identified in 4 individuals in 2 unrelated families with PCH, prenatal onset microcephaly, and arthrogryposis. In both families, the variant c.[1549_1550delAG]; [1486-3 C>G] segregated wth the phenotype. No CoA synthase protein was detected in patient cells by immunoblot analysis and CoA synthase activity was virtually absent. Partial CoA synthase defects were previously described by Dusi et al. (2014) PMID: 24360804 as a cause of COASY Protein-Associated Neurodegeneration (CoPAN), a type of Neurodegeneration and Brain Iron Accumulation (MIM: 615643). Dijk et al. (2018) PMID: 30089828 demonstrate that near complete loss of function variants in COASY are associated with lethal PCH and arthrogryposis.
Sources: Literature
Hypophosphataemia or rickets v0.9 SLC34A1 Ivone Leong edited their review of gene: SLC34A1: Added comment: Found an additional case of 2 siblings from Argentina who have hypophosphatemic nephrolithiasis/osteoporosis with a missense variant in SLC34A1.; Changed rating: GREEN; Changed publications: 12324554, 9560283, 25050900
Arthrogryposis v2.33 COASY Louise Daugherty Classified gene: COASY as Amber List (moderate evidence)
Arthrogryposis v2.33 COASY Louise Daugherty Added comment: Comment on list classification: New gene. Rated Amber until more cases on gene and disease association are reported.
Arthrogryposis v2.33 COASY Louise Daugherty Gene: coasy has been classified as Amber List (Moderate Evidence).
Arthrogryposis v2.32 COASY Louise Daugherty commented on gene: COASY: added watchlist tag
Severe microcephaly v1.42 COASY Louise Daugherty Publications for gene: COASY were set to 30089828
Arthrogryposis v2.32 COASY Louise Daugherty gene: COASY was added
gene: COASY was added to Arthrogryposis. Sources: Literature
watchlist tags were added to gene: COASY.
Mode of inheritance for gene: COASY was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COASY were set to 30089828; 24360804
Phenotypes for gene: COASY were set to Severe prenatal onset pontocerebellar hypoplasia, microcephaly, arthrogryposis
Review for gene: COASY was set to AMBER
Added comment: From Dijk et al. (2018) PMID: 30089828 variants in the gene Coenzyme A (CoA) synthase (COASY) gene, an enzyme essential in CoA synthesis. A single variant was identified in 4 individuals in 2 unrelated families with PCH, prenatal onset microcephaly, and arthrogryposis. In both families, the variant c.[1549_1550delAG]; [1486-3 C>G] segregated wth the phenotype. No CoA synthase protein was detected in patient cells by immunoblot analysis and CoA synthase activity was virtually absent. Partial CoA synthase defects were previously described by Dusi et al. (2014) PMID: 24360804 as a cause of COASY Protein-Associated Neurodegeneration (CoPAN), a type of Neurodegeneration and Brain Iron Accumulation (MIM: 615643). Dijk et al. (2018) PMID: 30089828 demonstrate that near complete loss of function variants in COASY are associated with lethal PCH and arthrogryposis.
Sources: Literature
Severe microcephaly v1.41 COASY Louise Daugherty commented on gene: COASY: added watchlist tag
Severe microcephaly v1.41 COASY Louise Daugherty Tag watchlist tag was added to gene: COASY.
Early onset or syndromic epilepsy v0.1303 SPR Sarah Leigh Phenotypes for gene: SPR were changed from to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency 612716
Severe microcephaly v1.41 COASY Louise Daugherty Classified gene: COASY as Amber List (moderate evidence)
Severe microcephaly v1.41 COASY Louise Daugherty Added comment: Comment on list classification: New gene. Rated Amber until more cases on gene and disease association are reported.
Severe microcephaly v1.41 COASY Louise Daugherty Gene: coasy has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1302 STAG1 Sarah Leigh Marked gene: STAG1 as ready
Early onset or syndromic epilepsy v0.1302 STAG1 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. Three missense variants and one copy number event that deletes STAG1 & PCCB genes were reported in four unrelated cases in which seizures were a phenotypic feature.
Early onset or syndromic epilepsy v0.1302 STAG1 Sarah Leigh Gene: stag1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1302 STAG1 Sarah Leigh Classified gene: STAG1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1302 STAG1 Sarah Leigh Gene: stag1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1301 STAG1 Sarah Leigh Publications for gene: STAG1 were set to
Severe microcephaly v1.40 COASY Louise Daugherty gene: COASY was added
gene: COASY was added to Severe microcephaly. Sources: Literature
Mode of inheritance for gene: COASY was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COASY were set to 30089828
Phenotypes for gene: COASY were set to Severe prenatal onset pontocerebellar hypoplasia, microcephaly, arthrogryposis
Review for gene: COASY was set to AMBER
Added comment: From Dijk et al. (2018) PMID: 30089828 variants in the gene Coenzyme A (CoA) synthase (COASY) gene, an enzyme essential in CoA synthesis. A single variant was identified in 4 individuals in 2 unrelated families with PCH, prenatal onset microcephaly, and arthrogryposis. In both families, the variant c.[1549_1550delAG]; [1486-3 C>G] segregated wth the phenotype. No CoA synthase protein was detected in patient cells by immunoblot analysis and CoA synthase activity was virtually absent. Partial CoA synthase defects were previously described by Dusi et al. (2014) PMID: 24360804 as a cause of COASY Protein-Associated Neurodegeneration (CoPAN), a type of Neurodegeneration and Brain Iron Accumulation (MIM: 615643). Dijk et al. (2018) PMID: 30089828 demonstrate that near complete loss of function variants in COASY are associated with lethal PCH and arthrogryposis.
Sources: Literature
Early onset or syndromic epilepsy v0.1300 STAG1 Sarah Leigh Phenotypes for gene: STAG1 were changed from to Mental retardation, autosomal dominant 47 617635
Hypophosphataemia or rickets v0.9 SLC34A1 Ivone Leong reviewed gene: SLC34A1: Rating: AMBER; Mode of pathogenicity: None; Publications: 12324554, 9560283; Phenotypes: ; Mode of inheritance: None
Early onset or syndromic epilepsy v0.1299 STAG1 Sarah Leigh Mode of inheritance for gene: STAG1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v0.1298 STAMBP Sarah Leigh Classified gene: STAMBP as Green List (high evidence)
Early onset or syndromic epilepsy v0.1298 STAMBP Sarah Leigh Gene: stambp has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1297 STAMBP Sarah Leigh Marked gene: STAMBP as ready
Early onset or syndromic epilepsy v0.1297 STAMBP Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 9 variants reported in at least 6 unrelated cases in which seizures are a phenotypic feature.
Early onset or syndromic epilepsy v0.1297 STAMBP Sarah Leigh Gene: stambp has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1297 STAMBP Sarah Leigh Publications for gene: STAMBP were set to
Early onset or syndromic epilepsy v0.1296 MMACHC Rebecca Foulger commented on gene: MMACHC
Early onset or syndromic epilepsy v0.1296 LARGE1 Ivone Leong Marked gene: LARGE1 as ready
Early onset or syndromic epilepsy v0.1296 LARGE1 Ivone Leong Added comment: Comment when marking as ready: Seizures are more common features of other dystroglycanopathies, therefore LARGE1 will remain an amber gene as there is not enough evidence to promote it to a green gene currently. I have added the 'watchlist' tag.
Early onset or syndromic epilepsy v0.1296 LARGE1 Ivone Leong Gene: large1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1296 LARGE1 Ivone Leong Tag watchlist tag was added to gene: LARGE1.
Early onset or syndromic epilepsy v0.1296 ISPD Ivone Leong Marked gene: ISPD as ready
Early onset or syndromic epilepsy v0.1296 ISPD Ivone Leong Added comment: Comment when marking as ready: Seizures are more common features of other dystroglycanopathies, therefore ISPD will remain an amber gene as there is not enough evidence to promote it to a green gene currently. I have added the 'watchlist' tag.
Early onset or syndromic epilepsy v0.1296 ISPD Ivone Leong Gene: ispd has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1296 ISPD Ivone Leong Tag watchlist tag was added to gene: ISPD.
Early onset or syndromic epilepsy v0.1296 STAMBP Sarah Leigh Phenotypes for gene: STAMBP were changed from to Microcephaly-capillary malformation syndrome 614261
Early onset or syndromic epilepsy v0.1295 HSPD1 Ivone Leong Marked gene: HSPD1 as ready
Early onset or syndromic epilepsy v0.1295 HSPD1 Ivone Leong Added comment: Comment when marking as ready: HSPD1 remains as an amber gene as there is not enough evidence to promote it to a green gene. I have added the watchlist tag.
Early onset or syndromic epilepsy v0.1295 HSPD1 Ivone Leong Gene: hspd1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1295 STAMBP Sarah Leigh Mode of inheritance for gene: STAMBP was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1294 HCCS Ivone Leong Marked gene: HCCS as ready
Early onset or syndromic epilepsy v0.1294 HCCS Ivone Leong Added comment: Comment when marking as ready: Despite seizures being listed as a common feature in GeneReviews, there is only 1 reported case of epilepsy with with HCCS gene. Therefore, it will remain as an amber gene. I have added the 'watchlist' tag.
Early onset or syndromic epilepsy v0.1294 HCCS Ivone Leong Gene: hccs has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1294 HCCS Ivone Leong Tag watchlist tag was added to gene: HCCS.
Early onset or syndromic epilepsy v0.1294 DOLK Rebecca Foulger Marked gene: DOLK as ready
Early onset or syndromic epilepsy v0.1294 DOLK Rebecca Foulger Gene: dolk has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1294 DOLK Rebecca Foulger commented on gene: DOLK: Added 'watchlist' tag.
Early onset or syndromic epilepsy v0.1294 DOLK Rebecca Foulger Tag watchlist tag was added to gene: DOLK.
Early onset or syndromic epilepsy v0.1294 DOLK Rebecca Foulger Classified gene: DOLK as Amber List (moderate evidence)
Early onset or syndromic epilepsy v0.1294 DOLK Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber: 2 families reported so far (2 siblings from PMID:23890587 and 1 of 2 cousins in PMID:17273964). Zornitza confirmed (via email on Dec 1st 2018) that there's no further known cases.
Early onset or syndromic epilepsy v0.1294 DOLK Rebecca Foulger Gene: dolk has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1293 GTPBP3 Ivone Leong Marked gene: GTPBP3 as ready
Early onset or syndromic epilepsy v0.1293 GTPBP3 Ivone Leong Added comment: Comment when marking as ready: GTPBP3 remains an amber gene as there are only 2 reported cases of epilepsy for this gene. I have put the 'watchlist' tag on so that if new cases appear this gene will be updated accordingly.
Early onset or syndromic epilepsy v0.1293 GTPBP3 Ivone Leong Gene: gtpbp3 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1293 GTPBP3 Ivone Leong Tag watchlist tag was added to gene: GTPBP3.
Early onset or syndromic epilepsy v0.1293 EXOSC3 Rebecca Foulger Marked gene: EXOSC3 as ready
Early onset or syndromic epilepsy v0.1293 EXOSC3 Rebecca Foulger Gene: exosc3 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1293 EXOSC3 Rebecca Foulger Classified gene: EXOSC3 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1293 EXOSC3 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Green review by Zornitza plus sufficient unrelated cases (>3) of seizures in patients with EXOSC3 variants from PMIDs:24524299 and 23284067 for inclusion on panel.
Early onset or syndromic epilepsy v0.1293 EXOSC3 Rebecca Foulger Gene: exosc3 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1292 EXOSC3 Rebecca Foulger commented on gene: EXOSC3: Rudnik-Schoneborn et al 2013 (PMID:23284067) detected biallelic variants in EXOSC3 in 15 patients (10 of 27 families). Epileptic seizures occurred in 3 patients in 2 families, including absence epilepsy in patient 2-1 and infantile spasms in 2 sisters (5-1 and 5-2).
Early onset or syndromic epilepsy v0.1292 MMACHC Rebecca Foulger Mode of inheritance for gene: MMACHC was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1291 MMACHC Rebecca Foulger Phenotypes for gene: MMACHC were changed from to Methylmalonic aciduria and homocystinuria, cblC type, 277400
Early onset or syndromic epilepsy v0.1290 MLC1 Rebecca Foulger Marked gene: MLC1 as ready
Early onset or syndromic epilepsy v0.1290 MLC1 Rebecca Foulger Gene: mlc1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1290 MLC1 Rebecca Foulger commented on gene: MLC1: In a woman with megalencephalic leukoencephalopathy with subcortical cysts-1 (MLC1; 604004), Lopez-Hernandez et al. (2011, PMID:21624973) identified a homozygous misssense 206C-T variant in the MLC1 gene (p.S69L). The patient had epilepsy amongst her symptoms.
Early onset or syndromic epilepsy v0.1290 MLC1 Rebecca Foulger Classified gene: MLC1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1290 MLC1 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Green review by Zornitza. Plus the onset of epileptic seizures is an integral part of the MLC phenotype (PMID:29466841) with plenty of seizure cases in MLC1 patients in PMIDs:29466841 and 21624973.
Early onset or syndromic epilepsy v0.1290 MLC1 Rebecca Foulger Gene: mlc1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1289 MLC1 Rebecca Foulger commented on gene: MLC1
Early onset or syndromic epilepsy v0.1289 MLC1 Rebecca Foulger Publications for gene: MLC1 were set to 21624973; 2946684
Early onset or syndromic epilepsy v0.1288 MLC1 Rebecca Foulger commented on gene: MLC1
Early onset or syndromic epilepsy v0.1288 MLC1 Rebecca Foulger Publications for gene: MLC1 were set to
Early onset or syndromic epilepsy v0.1287 MLC1 Rebecca Foulger Phenotypes for gene: MLC1 were changed from Megalencephalic leukoencephalopathy with subcortical cysts, 604004 to Megalencephalic leukoencephalopathy with subcortical cysts, 604004; generalized tonic-clonic seizures; focal seizures
Early onset or syndromic epilepsy v0.1286 MLC1 Rebecca Foulger Mode of inheritance for gene: MLC1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1285 MLC1 Rebecca Foulger Phenotypes for gene: MLC1 were changed from to Megalencephalic leukoencephalopathy with subcortical cysts, 604004
Limb disorders v0.337 ZSWIM6 Eleanor Williams Classified gene: ZSWIM6 as No list
Limb disorders v0.337 ZSWIM6 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.337 ZSWIM6 Eleanor Williams Gene: zswim6 has been removed from the panel.
Limb disorders v0.336 WDR35 Eleanor Williams Classified gene: WDR35 as No list
Limb disorders v0.336 WDR35 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.336 WDR35 Eleanor Williams Gene: wdr35 has been removed from the panel.
Limb disorders v0.335 WDR34 Eleanor Williams Classified gene: WDR34 as No list
Limb disorders v0.335 WDR34 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.335 WDR34 Eleanor Williams Gene: wdr34 has been removed from the panel.
Limb disorders v0.334 WDR19 Eleanor Williams Classified gene: WDR19 as No list
Limb disorders v0.334 WDR19 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.334 WDR19 Eleanor Williams Gene: wdr19 has been removed from the panel.
Limb disorders v0.333 WDPCP Eleanor Williams Classified gene: WDPCP as No list
Limb disorders v0.333 WDPCP Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.333 WDPCP Eleanor Williams Gene: wdpcp has been removed from the panel.
Limb disorders v0.332 TTC8 Eleanor Williams Marked gene: TTC8 as ready
Limb disorders v0.332 TTC8 Eleanor Williams Gene: ttc8 has been removed from the panel.
Limb disorders v0.332 TTC8 Eleanor Williams Classified gene: TTC8 as No list
Limb disorders v0.332 TTC8 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.332 TTC8 Eleanor Williams Gene: ttc8 has been removed from the panel.
Limb disorders v0.331 TTC21B Eleanor Williams Marked gene: TTC21B as ready
Limb disorders v0.331 TTC21B Eleanor Williams Gene: ttc21b has been removed from the panel.
Limb disorders v0.331 TTC21B Eleanor Williams Classified gene: TTC21B as No list
Limb disorders v0.331 TTC21B Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.331 TTC21B Eleanor Williams Gene: ttc21b has been removed from the panel.
Limb disorders v0.330 TRAF3IP1 Eleanor Williams Marked gene: TRAF3IP1 as ready
Limb disorders v0.330 TRAF3IP1 Eleanor Williams Gene: traf3ip1 has been removed from the panel.
Limb disorders v0.330 TRAF3IP1 Eleanor Williams Classified gene: TRAF3IP1 as No list
Limb disorders v0.330 TRAF3IP1 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.330 TRAF3IP1 Eleanor Williams Gene: traf3ip1 has been removed from the panel.
Limb disorders v0.329 TMEM67 Eleanor Williams Marked gene: TMEM67 as ready
Limb disorders v0.329 TMEM67 Eleanor Williams Gene: tmem67 has been removed from the panel.
Limb disorders v0.329 TMEM67 Eleanor Williams Classified gene: TMEM67 as No list
Limb disorders v0.329 TMEM67 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.329 TMEM67 Eleanor Williams Gene: tmem67 has been removed from the panel.
Limb disorders v0.328 TMEM237 Eleanor Williams Marked gene: TMEM237 as ready
Limb disorders v0.328 TMEM237 Eleanor Williams Gene: tmem237 has been removed from the panel.
Limb disorders v0.328 TMEM237 Eleanor Williams Classified gene: TMEM237 as No list
Limb disorders v0.328 TMEM237 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.328 TMEM237 Eleanor Williams Gene: tmem237 has been removed from the panel.
Limb disorders v0.327 TMEM231 Eleanor Williams Marked gene: TMEM231 as ready
Limb disorders v0.327 TMEM231 Eleanor Williams Gene: tmem231 has been removed from the panel.
Limb disorders v0.327 TMEM231 Eleanor Williams Classified gene: TMEM231 as No list
Limb disorders v0.327 TMEM231 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.327 TMEM231 Eleanor Williams Gene: tmem231 has been removed from the panel.
Limb disorders v0.326 TMEM216 Eleanor Williams Marked gene: TMEM216 as ready
Limb disorders v0.326 TMEM216 Eleanor Williams Gene: tmem216 has been removed from the panel.
Limb disorders v0.326 TMEM216 Eleanor Williams Classified gene: TMEM216 as No list
Limb disorders v0.326 TMEM216 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.326 TMEM216 Eleanor Williams Gene: tmem216 has been removed from the panel.
Limb disorders v0.325 TMEM138 Eleanor Williams Marked gene: TMEM138 as ready
Limb disorders v0.325 TMEM138 Eleanor Williams Gene: tmem138 has been removed from the panel.
Limb disorders v0.325 TMEM138 Eleanor Williams Classified gene: TMEM138 as No list
Limb disorders v0.325 TMEM138 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.325 TMEM138 Eleanor Williams Gene: tmem138 has been removed from the panel.
Limb disorders v0.324 TCTN3 Eleanor Williams Classified gene: TCTN3 as No list
Limb disorders v0.324 TCTN3 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.324 TCTN3 Eleanor Williams Gene: tctn3 has been removed from the panel.
Limb disorders v0.323 TCTN2 Eleanor Williams Classified gene: TCTN2 as No list
Limb disorders v0.323 TCTN2 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.323 TCTN2 Eleanor Williams Gene: tctn2 has been removed from the panel.
Limb disorders v0.322 TCTEX1D2 Eleanor Williams Classified gene: TCTEX1D2 as No list
Limb disorders v0.322 TCTEX1D2 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.322 TCTEX1D2 Eleanor Williams Gene: tctex1d2 has been removed from the panel.
Limb disorders v0.321 SDCCAG8 Eleanor Williams Marked gene: SDCCAG8 as ready
Limb disorders v0.321 SDCCAG8 Eleanor Williams Gene: sdccag8 has been removed from the panel.
Limb disorders v0.321 SDCCAG8 Eleanor Williams Classified gene: SDCCAG8 as No list
Limb disorders v0.321 SDCCAG8 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.321 SDCCAG8 Eleanor Williams Gene: sdccag8 has been removed from the panel.
Limb disorders v0.320 RPGRIP1L Eleanor Williams Marked gene: RPGRIP1L as ready
Limb disorders v0.320 RPGRIP1L Eleanor Williams Gene: rpgrip1l has been removed from the panel.
Limb disorders v0.320 RPGRIP1L Eleanor Williams Classified gene: RPGRIP1L as No list
Limb disorders v0.320 RPGRIP1L Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.320 RPGRIP1L Eleanor Williams Gene: rpgrip1l has been removed from the panel.
Limb disorders v0.319 OFD1 Eleanor Williams Marked gene: OFD1 as ready
Limb disorders v0.319 OFD1 Eleanor Williams Gene: ofd1 has been removed from the panel.
Limb disorders v0.319 OFD1 Eleanor Williams Classified gene: OFD1 as No list
Limb disorders v0.319 OFD1 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.319 OFD1 Eleanor Williams Gene: ofd1 has been removed from the panel.
Limb disorders v0.318 NPHP3 Eleanor Williams Marked gene: NPHP3 as ready
Limb disorders v0.318 NPHP3 Eleanor Williams Gene: nphp3 has been removed from the panel.
Limb disorders v0.318 NPHP3 Eleanor Williams Classified gene: NPHP3 as No list
Limb disorders v0.318 NPHP3 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.318 NPHP3 Eleanor Williams Gene: nphp3 has been removed from the panel.
Limb disorders v0.317 NEK1 Eleanor Williams Classified gene: NEK1 as No list
Limb disorders v0.317 NEK1 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.317 NEK1 Eleanor Williams Gene: nek1 has been removed from the panel.
Limb disorders v0.316 MKS1 Eleanor Williams Marked gene: MKS1 as ready
Limb disorders v0.316 MKS1 Eleanor Williams Gene: mks1 has been removed from the panel.
Limb disorders v0.316 MKS1 Eleanor Williams Classified gene: MKS1 as No list
Limb disorders v0.316 MKS1 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.316 MKS1 Eleanor Williams Gene: mks1 has been removed from the panel.
Limb disorders v0.315 MKKS Eleanor Williams Marked gene: MKKS as ready
Limb disorders v0.315 MKKS Eleanor Williams Gene: mkks has been removed from the panel.
Limb disorders v0.315 MKKS Eleanor Williams Classified gene: MKKS as No list
Limb disorders v0.315 MKKS Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.315 MKKS Eleanor Williams Gene: mkks has been removed from the panel.
Limb disorders v0.314 KIF7 Eleanor Williams Marked gene: KIF7 as ready
Limb disorders v0.314 KIF7 Eleanor Williams Gene: kif7 has been removed from the panel.
Limb disorders v0.314 KIF7 Eleanor Williams Classified gene: KIF7 as No list
Limb disorders v0.314 KIF7 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.314 KIF7 Eleanor Williams Gene: kif7 has been removed from the panel.
Limb disorders v0.313 KIAA0586 Eleanor Williams Classified gene: KIAA0586 as No list
Limb disorders v0.313 KIAA0586 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.313 KIAA0586 Eleanor Williams Gene: kiaa0586 has been removed from the panel.
Limb disorders v0.312 INPP5E Eleanor Williams Marked gene: INPP5E as ready
Limb disorders v0.312 INPP5E Eleanor Williams Gene: inpp5e has been removed from the panel.
Limb disorders v0.312 INPP5E Eleanor Williams Classified gene: INPP5E as No list
Limb disorders v0.312 INPP5E Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.312 INPP5E Eleanor Williams Gene: inpp5e has been removed from the panel.
Limb disorders v0.311 IFT80 Eleanor Williams Marked gene: IFT80 as ready
Limb disorders v0.311 IFT80 Eleanor Williams Gene: ift80 has been removed from the panel.
Limb disorders v0.311 IFT80 Eleanor Williams Classified gene: IFT80 as No list
Limb disorders v0.311 IFT80 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.311 IFT80 Eleanor Williams Gene: ift80 has been removed from the panel.
Limb disorders v0.310 IFT52 Eleanor Williams Classified gene: IFT52 as No list
Limb disorders v0.310 IFT52 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.310 IFT52 Eleanor Williams Gene: ift52 has been removed from the panel.
Limb disorders v0.309 IFT172 Eleanor Williams Marked gene: IFT172 as ready
Limb disorders v0.309 IFT172 Eleanor Williams Gene: ift172 has been removed from the panel.
Limb disorders v0.309 IFT172 Eleanor Williams Classified gene: IFT172 as No list
Limb disorders v0.309 IFT172 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.309 IFT172 Eleanor Williams Gene: ift172 has been removed from the panel.
Limb disorders v0.308 IFT140 Eleanor Williams Marked gene: IFT140 as ready
Limb disorders v0.308 IFT140 Eleanor Williams Gene: ift140 has been removed from the panel.
Limb disorders v0.308 IFT140 Eleanor Williams Classified gene: IFT140 as No list
Limb disorders v0.308 IFT140 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.308 IFT140 Eleanor Williams Gene: ift140 has been removed from the panel.
Limb disorders v0.307 ICK Eleanor Williams Classified gene: ICK as No list
Limb disorders v0.307 ICK Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.307 ICK Eleanor Williams Gene: ick has been removed from the panel.
Limb disorders v0.306 HYLS1 Eleanor Williams Marked gene: HYLS1 as ready
Limb disorders v0.306 HYLS1 Eleanor Williams Gene: hyls1 has been removed from the panel.
Limb disorders v0.306 HYLS1 Eleanor Williams Classified gene: HYLS1 as No list
Limb disorders v0.306 HYLS1 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.306 HYLS1 Eleanor Williams Gene: hyls1 has been removed from the panel.
Limb disorders v0.305 EVC2 Eleanor Williams Marked gene: EVC2 as ready
Limb disorders v0.305 EVC2 Eleanor Williams Gene: evc2 has been removed from the panel.
Limb disorders v0.305 EVC2 Eleanor Williams Classified gene: EVC2 as No list
Limb disorders v0.305 EVC2 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.305 EVC2 Eleanor Williams Gene: evc2 has been removed from the panel.
Limb disorders v0.304 EVC Eleanor Williams Marked gene: EVC as ready
Limb disorders v0.304 EVC Eleanor Williams Gene: evc has been removed from the panel.
Limb disorders v0.304 EVC Eleanor Williams Classified gene: EVC as No list
Limb disorders v0.304 EVC Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.304 EVC Eleanor Williams Gene: evc has been removed from the panel.
Limb disorders v0.303 DYNC2LI1 Eleanor Williams Marked gene: DYNC2LI1 as ready
Limb disorders v0.303 DYNC2LI1 Eleanor Williams Gene: dync2li1 has been removed from the panel.
Limb disorders v0.303 DYNC2LI1 Eleanor Williams Classified gene: DYNC2LI1 as No list
Limb disorders v0.303 DYNC2LI1 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.303 DYNC2LI1 Eleanor Williams Gene: dync2li1 has been removed from the panel.
Limb disorders v0.302 DYNC2H1 Eleanor Williams Classified gene: DYNC2H1 as No list
Limb disorders v0.302 DYNC2H1 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.302 DYNC2H1 Eleanor Williams Gene: dync2h1 has been removed from the panel.
Limb disorders v0.301 DDX59 Eleanor Williams Classified gene: DDX59 as No list
Limb disorders v0.301 DDX59 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.301 DDX59 Eleanor Williams Gene: ddx59 has been removed from the panel.
Limb disorders v0.300 CSPP1 Eleanor Williams Marked gene: CSPP1 as ready
Limb disorders v0.300 CSPP1 Eleanor Williams Gene: cspp1 has been removed from the panel.
Limb disorders v0.300 CSPP1 Eleanor Williams Classified gene: CSPP1 as No list
Limb disorders v0.300 CSPP1 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.300 CSPP1 Eleanor Williams Gene: cspp1 has been removed from the panel.
Limb disorders v0.299 CEP41 Eleanor Williams Marked gene: CEP41 as ready
Limb disorders v0.299 CEP41 Eleanor Williams Gene: cep41 has been removed from the panel.
Limb disorders v0.299 CEP41 Eleanor Williams Classified gene: CEP41 as No list
Limb disorders v0.299 CEP41 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.299 CEP41 Eleanor Williams Gene: cep41 has been removed from the panel.
Limb disorders v0.298 CEP290 Eleanor Williams Marked gene: CEP290 as ready
Limb disorders v0.298 CEP290 Eleanor Williams Gene: cep290 has been removed from the panel.
Limb disorders v0.298 CEP290 Eleanor Williams Classified gene: CEP290 as No list
Limb disorders v0.298 CEP290 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.298 CEP290 Eleanor Williams Gene: cep290 has been removed from the panel.
Limb disorders v0.297 CEP164 Eleanor Williams Marked gene: CEP164 as ready
Limb disorders v0.297 CEP164 Eleanor Williams Gene: cep164 has been removed from the panel.
Limb disorders v0.297 CEP164 Eleanor Williams Classified gene: CEP164 as No list
Limb disorders v0.297 CEP164 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.297 CEP164 Eleanor Williams Gene: cep164 has been removed from the panel.
Limb disorders v0.296 CEP120 Eleanor Williams Marked gene: CEP120 as ready
Limb disorders v0.296 CEP120 Eleanor Williams Gene: cep120 has been removed from the panel.
Limb disorders v0.296 CEP120 Eleanor Williams Classified gene: CEP120 as No list
Limb disorders v0.296 CEP120 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.296 CEP120 Eleanor Williams Gene: cep120 has been removed from the panel.
Limb disorders v0.295 CENPF Eleanor Williams Marked gene: CENPF as ready
Limb disorders v0.295 CENPF Eleanor Williams Gene: cenpf has been removed from the panel.
Limb disorders v0.295 CENPF Eleanor Williams Classified gene: CENPF as No list
Limb disorders v0.295 CENPF Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.295 CENPF Eleanor Williams Gene: cenpf has been removed from the panel.
Limb disorders v0.294 CC2D2A Eleanor Williams Marked gene: CC2D2A as ready
Limb disorders v0.294 CC2D2A Eleanor Williams Gene: cc2d2a has been removed from the panel.
Limb disorders v0.294 CC2D2A Eleanor Williams Classified gene: CC2D2A as No list
Limb disorders v0.294 CC2D2A Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.294 CC2D2A Eleanor Williams Gene: cc2d2a has been removed from the panel.
Limb disorders v0.293 C5orf42 Eleanor Williams Marked gene: C5orf42 as ready
Limb disorders v0.293 C5orf42 Eleanor Williams Gene: c5orf42 has been removed from the panel.
Limb disorders v0.293 C5orf42 Eleanor Williams Classified gene: C5orf42 as No list
Limb disorders v0.293 C5orf42 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.293 C5orf42 Eleanor Williams Gene: c5orf42 has been removed from the panel.
Limb disorders v0.292 C2CD3 Eleanor Williams Marked gene: C2CD3 as ready
Limb disorders v0.292 C2CD3 Eleanor Williams Gene: c2cd3 has been removed from the panel.
Limb disorders v0.292 C2CD3 Eleanor Williams Classified gene: C2CD3 as No list
Limb disorders v0.292 C2CD3 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.292 C2CD3 Eleanor Williams Gene: c2cd3 has been removed from the panel.
Limb disorders v0.291 BBS9 Eleanor Williams Marked gene: BBS9 as ready
Limb disorders v0.291 BBS9 Eleanor Williams Gene: bbs9 has been removed from the panel.
Limb disorders v0.291 BBS9 Eleanor Williams Classified gene: BBS9 as No list
Limb disorders v0.291 BBS9 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.291 BBS9 Eleanor Williams Gene: bbs9 has been removed from the panel.
Limb disorders v0.290 BBS7 Eleanor Williams Marked gene: BBS7 as ready
Limb disorders v0.290 BBS7 Eleanor Williams Gene: bbs7 has been removed from the panel.
Limb disorders v0.290 BBS7 Eleanor Williams Classified gene: BBS7 as No list
Limb disorders v0.290 BBS7 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.290 BBS7 Eleanor Williams Gene: bbs7 has been removed from the panel.
Limb disorders v0.289 BBS5 Eleanor Williams Marked gene: BBS5 as ready
Limb disorders v0.289 BBS5 Eleanor Williams Gene: bbs5 has been removed from the panel.
Limb disorders v0.289 BBS5 Eleanor Williams Classified gene: BBS5 as No list
Limb disorders v0.289 BBS5 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.289 BBS5 Eleanor Williams Gene: bbs5 has been removed from the panel.
Limb disorders v0.288 BBS4 Eleanor Williams Marked gene: BBS4 as ready
Limb disorders v0.288 BBS4 Eleanor Williams Gene: bbs4 has been removed from the panel.
Limb disorders v0.288 BBS4 Eleanor Williams Classified gene: BBS4 as No list
Limb disorders v0.288 BBS4 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.288 BBS4 Eleanor Williams Gene: bbs4 has been removed from the panel.
Limb disorders v0.287 BBS2 Eleanor Williams Marked gene: BBS2 as ready
Limb disorders v0.287 BBS2 Eleanor Williams Gene: bbs2 has been removed from the panel.
Limb disorders v0.287 BBS2 Eleanor Williams Classified gene: BBS2 as No list
Limb disorders v0.287 BBS2 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.287 BBS2 Eleanor Williams Gene: bbs2 has been removed from the panel.
Limb disorders v0.286 BBS12 Eleanor Williams Marked gene: BBS12 as ready
Limb disorders v0.286 BBS12 Eleanor Williams Gene: bbs12 has been removed from the panel.
Limb disorders v0.286 BBS12 Eleanor Williams Classified gene: BBS12 as No list
Limb disorders v0.286 BBS12 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.286 BBS12 Eleanor Williams Gene: bbs12 has been removed from the panel.
Limb disorders v0.285 BBS10 Eleanor Williams Marked gene: BBS10 as ready
Limb disorders v0.285 BBS10 Eleanor Williams Gene: bbs10 has been removed from the panel.
Limb disorders v0.285 BBS10 Eleanor Williams Classified gene: BBS10 as No list
Limb disorders v0.285 BBS10 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.285 BBS10 Eleanor Williams Gene: bbs10 has been removed from the panel.
Limb disorders v0.284 BBS1 Eleanor Williams Classified gene: BBS1 as No list
Limb disorders v0.284 BBS1 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.284 BBS1 Eleanor Williams Gene: bbs1 has been removed from the panel.
Limb disorders v0.283 B9D2 Eleanor Williams Classified gene: B9D2 as No list
Limb disorders v0.283 B9D2 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.283 B9D2 Eleanor Williams Gene: b9d2 has been removed from the panel.
Limb disorders v0.282 ARL6 Eleanor Williams Classified gene: ARL6 as No list
Limb disorders v0.282 ARL6 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.282 ARL6 Eleanor Williams Gene: arl6 has been removed from the panel.
Limb disorders v0.281 ALMS1 Eleanor Williams Classified gene: ALMS1 as No list
Limb disorders v0.281 ALMS1 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.281 ALMS1 Eleanor Williams Gene: alms1 has been removed from the panel.
Limb disorders v0.280 AHI1 Eleanor Williams Classified gene: AHI1 as No list
Limb disorders v0.280 AHI1 Eleanor Williams Added comment: Comment on list classification: Gene made grey as it is green on the Rare multisystem ciliopathy disorders panel (v1.78) and the ciliopathy panel will be applied if a patient is suspected of having a ciliopathy, or the possibility of a ciliopathy cannot be excluded.
Limb disorders v0.280 AHI1 Eleanor Williams Gene: ahi1 has been removed from the panel.
Limb disorders v0.279 GLI3 Eleanor Williams Marked gene: GLI3 as ready
Limb disorders v0.279 GLI3 Eleanor Williams Gene: gli3 has been classified as Green List (High Evidence).
Limb disorders v0.279 GLI3 Eleanor Williams Classified gene: GLI3 as Green List (high evidence)
Limb disorders v0.279 GLI3 Eleanor Williams Added comment: Comment on list classification: Keeping this gene green on the Limb disorders panel, although it is also green on the Rare multisystem ciliopathies panel, on advice of Genomics England clinical team.
Limb disorders v0.279 GLI3 Eleanor Williams Gene: gli3 has been classified as Green List (High Evidence).
Limb disorders v0.278 TCTEX1D2 Eleanor Williams Source Expert Review Removed was added to TCTEX1D2.
Rating Changed from Amber List (moderate evidence) to No List (delete)
Limb disorders v0.278 WDR34 Eleanor Williams Source Expert Review Removed was added to WDR34.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 DDX59 Eleanor Williams Source Expert Review Removed was added to DDX59.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 WDR35 Eleanor Williams Source Expert Review Removed was added to WDR35.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 WDPCP Eleanor Williams Source Expert Review Removed was added to WDPCP.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 WDR19 Eleanor Williams Source Expert Review Removed was added to WDR19.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 TCTN3 Eleanor Williams Source Expert Review Removed was added to TCTN3.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 B9D2 Eleanor Williams Source Expert Review Removed was added to B9D2.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 AHI1 Eleanor Williams Source Expert Review Removed was added to AHI1.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 TCTN2 Eleanor Williams Source Expert Review Removed was added to TCTN2.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 BBS1 Eleanor Williams Source Expert Review Removed was added to BBS1.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 ARL6 Eleanor Williams Source Expert Review Removed was added to ARL6.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 ALMS1 Eleanor Williams Source Expert Review Removed was added to ALMS1.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 CENPF Eleanor Williams Source Expert Review Removed was added to CENPF.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 DYNC2LI1 Eleanor Williams Source Expert Review Removed was added to DYNC2LI1.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 IFT140 Eleanor Williams Source Expert Review Removed was added to IFT140.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 NEK1 Eleanor Williams Source Expert Review Removed was added to NEK1.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 DYNC2H1 Eleanor Williams Source Expert Review Removed was added to DYNC2H1.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 IFT80 Eleanor Williams Source Expert Review Removed was added to IFT80.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 IFT52 Eleanor Williams Source Expert Review Removed was added to IFT52.
Rating Changed from Amber List (moderate evidence) to No List (delete)
Limb disorders v0.278 CEP120 Eleanor Williams Source Expert Review Removed was added to CEP120.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 TRAF3IP1 Eleanor Williams Source Expert Review Removed was added to TRAF3IP1.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 IFT172 Eleanor Williams Source Expert Review Removed was added to IFT172.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 NPHP3 Eleanor Williams Source Expert Review Removed was added to NPHP3.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 ICK Eleanor Williams Source Expert Review Removed was added to ICK.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 ZSWIM6 Eleanor Williams Source Expert Review Removed was added to ZSWIM6.
Rating Changed from Amber List (moderate evidence) to No List (delete)
Limb disorders v0.278 C2CD3 Eleanor Williams Source Expert Review Removed was added to C2CD3.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 TTC21B Eleanor Williams Source Expert Review Removed was added to TTC21B.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 CEP164 Eleanor Williams Source Expert Review Removed was added to CEP164.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 TMEM67 Eleanor Williams Source Expert Review Removed was added to TMEM67.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 TMEM216 Eleanor Williams Source Expert Review Removed was added to TMEM216.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 KIAA0586 Eleanor Williams Source Expert Review Removed was added to KIAA0586.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 C5orf42 Eleanor Williams Source Expert Review Removed was added to C5orf42.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 RPGRIP1L Eleanor Williams Source Expert Review Removed was added to RPGRIP1L.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 CSPP1 Eleanor Williams Source Expert Review Removed was added to CSPP1.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 TMEM237 Eleanor Williams Source Expert Review Removed was added to TMEM237.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 INPP5E Eleanor Williams Source Expert Review Removed was added to INPP5E.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 TMEM138 Eleanor Williams Source Expert Review Removed was added to TMEM138.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 CC2D2A Eleanor Williams Source Expert Review Removed was added to CC2D2A.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 TMEM231 Eleanor Williams Source Expert Review Removed was added to TMEM231.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 CEP41 Eleanor Williams Source Expert Review Removed was added to CEP41.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 KIF7 Eleanor Williams Source Expert Review Removed was added to KIF7.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 OFD1 Eleanor Williams Source Expert Review Removed was added to OFD1.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 HYLS1 Eleanor Williams Source Expert Review Removed was added to HYLS1.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 CEP290 Eleanor Williams Source Expert Review Removed was added to CEP290.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 EVC2 Eleanor Williams Source Expert Review Removed was added to EVC2.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 EVC Eleanor Williams Source Expert Review Removed was added to EVC.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 SDCCAG8 Eleanor Williams Source Expert Review Removed was added to SDCCAG8.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 MKS1 Eleanor Williams Source Expert Review Removed was added to MKS1.
Rating Changed from Green List (high evidence) to No List (delete)
Limb disorders v0.278 BBS9 Eleanor Williams Source Expert Review Removed was added to BBS9.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 TTC8 Eleanor Williams Source Expert Review Removed was added to TTC8.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 BBS7 Eleanor Williams Source Expert Review Removed was added to BBS7.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 MKKS Eleanor Williams Source Expert Review Removed was added to MKKS.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 BBS5 Eleanor Williams Source Expert Review Removed was added to BBS5.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 BBS4 Eleanor Williams Source Expert Review Removed was added to BBS4.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 BBS2 Eleanor Williams Source Expert Review Removed was added to BBS2.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 BBS12 Eleanor Williams Source Expert Review Removed was added to BBS12.
Rating Changed from Red List (low evidence) to No List (delete)
Limb disorders v0.278 BBS10 Eleanor Williams Source Expert Review Removed was added to BBS10.
Rating Changed from Red List (low evidence) to No List (delete)
Intellectual disability v2.562 PHF21A Konstantinos Varvagiannis reviewed gene: PHF21A: Rating: GREEN; Mode of pathogenicity: None; Publications: 22770980, 30487643; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Early onset or syndromic epilepsy v0.1284 RALA Konstantinos Varvagiannis gene: RALA was added
gene: RALA was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: RALA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: RALA were set to Global developmental delay; Intellectual disability; Seizures; Abnormality of nervous system morphology
Penetrance for gene: RALA were set to unknown
Mode of pathogenicity for gene: RALA was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: RALA was set to GREEN
Added comment: Hiatt et al. (doi.org/10.1371/journal.pgen.1007671) report on 11 individuals (incl. a pair of monozygotic twins) from 10 unrelated families, most (10/11) with de novo mutations in RALA.

DD/ID was a prominent feature (the authors note that ID was specifically noted in 8 but could not be excluded in 3 further individuals who appear to be very young in the table). Structural brain anomalies (9/11), seizures (6/11) and common facial features were also noted.

RALA belongs to the RAS superfamily of small GTPases.

5 different de novo missense variants and 1 in-frame deletion, all within a GTP/GDP binding region of RALA (although appart in the protein primary structure) were observed. 7 occurrences of missense variants concerned Val25 and Lys128 (V25M, V25L, K128R), one Asp130 (D130G) and a further one Ser157 (S157A). The in-frame deletion concerned Ala158.

Missense variants in corresponding positions of RAS proteins (HRAS/KRAS/NRAS) have been reported in RASopathies, while the authors observed some phenotypic overlap with the latter group of disorders (DD/ID, growth delay, macrocephaly, high forehead and position of ears).

Functional studies demonstrated reduction in GTPase activity (for all variants) and altered RALA effector binding (for most reduction - in the case of S157A, increase).

Several lines of evidence are provided to show that alteration of the GTP/GTP-binding rather than a dosage effect is considered the likely mechanism. RALA is depleted in missense mutations in its GTP/GDP binding domain.

For these reasons and others (segregation studies not possible, variant observed 2x in Bravo database, phenotypic differences compared to the rest of the cohort, ROH suggesting parental consanguinity in the specific individual) the single nonsense variant (R176X) reported in the study is considered a VUS.

Seizures were a feature in most (6/11) individuals (5 different variants incl. R176X). Discordance for this feature was however noted for individuals with the same variant.

As a result, this gene can be considered for inclusion in this panel as green (or amber).
Sources: Literature
Intellectual disability v2.562 RALA Konstantinos Varvagiannis gene: RALA was added
gene: RALA was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: RALA was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: RALA were set to Global developmental delay; Intellectual disability; Seizures; Abnormality of nervous system morphology
Penetrance for gene: RALA were set to unknown
Mode of pathogenicity for gene: RALA was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: RALA was set to GREEN
Added comment: Hiatt et al. (doi.org/10.1371/journal.pgen.1007671) report on 11 individuals (incl. a pair of monozygotic twins) from 10 unrelated families, most (10/11) with de novo mutations in RALA.

DD/ID was a prominent feature (the authors note that ID was specifically noted in 8 but could not be excluded in 3 further individuals who appear to be very young in the table). Structural brain anomalies (9/11), seizures (6/11) and common facial features were also noted.

RALA belongs to the RAS superfamily of small GTPases.

5 different de novo missense variants and 1 in-frame deletion, all within a GTP/GDP binding region of RALA (although appart in the protein primary structure) were observed. 7 occurrences of missense variants concerned Val25 and Lys128 (V25M, V25L, K128R), one Asp130 (D130G) and a further one Ser157 (S157A). The in-frame deletion concerned Ala158.

Missense variants in corresponding positions of RAS proteins (HRAS/KRAS/NRAS) have been reported in RASopathies, while the authors observed some phenotypic overlap with the latter group of disorders (DD/ID, growth delay, macrocephaly, high forehead and position of ears).

Functional studies demonstrated reduction in GTPase activity (for all variants) and altered RALA effector binding (for most reduction - in the case of S157A, increase).

Several lines of evidence are provided to show that alteration of the GTP/GTP-binding rather than a dosage effect is considered the likely mechanism. RALA is depleted in missense mutations in its GTP/GDP binding domain.

For these reasons and others (segregation studies not possible, variant observed 2x in Bravo database, phenotypic differences compared to the rest of the cohort, ROH suggesting parental consanguinity in the specific individual) the single nonsense variant (R176X) reported in the study is considered a VUS.

As a result, this gene can be considered for inclusion in this panel as green.
Sources: Literature
Early onset or syndromic epilepsy v0.1284 SCO2 Sarah Leigh Mode of inheritance for gene: SCO2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1283 SCO2 Sarah Leigh Publications for gene: SCO2 were set to
Early onset or syndromic epilepsy v0.1282 SCO2 Sarah Leigh Phenotypes for gene: SCO2 were changed from to Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1, 604377
Early onset or syndromic epilepsy v0.1281 SCO1 Sarah Leigh Classified gene: SCO1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1281 SCO1 Sarah Leigh Gene: sco1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1280 SCO1 Sarah Leigh Marked gene: SCO1 as ready
Early onset or syndromic epilepsy v0.1280 SCO1 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 3 variants reported in unrelated cases
Early onset or syndromic epilepsy v0.1280 SCO1 Sarah Leigh Gene: sco1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v2.562 RORB Louise Daugherty gene: RORB was added
gene: RORB was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: RORB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RORB were set to 27352968; 24355400
Phenotypes for gene: RORB were set to generalized epilepsies with predominant absence seizures, intellectual disability
Review for gene: RORB was set to RED
Added comment: PMID 27352968 identified a patient with intellectual disability and a balanced translocation where one breakpoint truncates RORB and also found two de novo deletions in patients with behavioral and cognitive impairment and epilepsy: a 52-kb microdeletion involving exons 5-10 of RORB and a larger 9q21-microdeletion.
Sources: Literature
Early onset or syndromic epilepsy v0.1280 SCO1 Sarah Leigh Phenotypes for gene: SCO1 were changed from to Mitochondrial complex IV deficiency, 220110
Early onset or syndromic epilepsy v0.1279 SCO1 Sarah Leigh Publications for gene: SCO1 were set to 23878101; 11013136; 19295170
Early onset or syndromic epilepsy v0.1279 SCO1 Sarah Leigh Publications for gene: SCO1 were set to
Early onset or syndromic epilepsy v0.1278 SCO1 Sarah Leigh Mode of inheritance for gene: SCO1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1277 RORB Sarah Leigh Marked gene: RORB as ready
Early onset or syndromic epilepsy v0.1277 RORB Sarah Leigh Added comment: Comment when marking as ready: Not associated with phenotype in OMIM or in Gen2Phen. Three variants reported in three unrelated cases of generalized epilepsies with predominant absence seizures. The variant c.196C>T/p.(Arg66*) segregates with the condition in four affected members of a three generation family. Variants c.218T>C/p.(Leu73Pro), c.1249_1251delACG/p.(Thr417del) appeared to be the result of de novo events in sporadic cases. Furthermore, two de novo deletions were identified in patients with behavioral and cognitive impairment and epilepsy: a 52-kb microdeletion involving exons 5-10 of RORB and a larger 9q21-microdeletion (PMID: 27352968).
Early onset or syndromic epilepsy v0.1277 RORB Sarah Leigh Gene: rorb has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1277 RORB Sarah Leigh Classified gene: RORB as Green List (high evidence)
Early onset or syndromic epilepsy v0.1277 RORB Sarah Leigh Gene: rorb has been classified as Green List (High Evidence).
Hypophosphataemia or rickets v0.9 FGFR1 Ivone Leong reviewed gene: FGFR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15625620, 20236123; Phenotypes: ; Mode of inheritance: None
Intellectual disability v2.561 MAB21L1 Konstantinos Varvagiannis gene: MAB21L1 was added
gene: MAB21L1 was added to Intellectual disability. Sources: Literature,Expert Review
Mode of inheritance for gene: MAB21L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAB21L1 were set to 27103078
Phenotypes for gene: MAB21L1 were set to Global developmental delay; Intellectual disability; Cerebellar hypoplasia; Abnormality of the eye; Abnormality of the genital system
Penetrance for gene: MAB21L1 were set to Complete
Review for gene: MAB21L1 was set to GREEN
gene: MAB21L1 was marked as current diagnostic
Added comment: Bruel et al. (PMID: 27103078) report on a boy, born to consanguineous Algerian parents, homozygous for a frameshift MAB21L1 variant.

Rad et al. (http://dx.doi.org/10.1136/jmedgenet-2018-105623) describe 10 additional individuals from 5 unrelated consanguineous families (from Iran, Lebanon and Turkey). These subjects were homozygous for truncating variants appart from a patient with a missense one [NM_005584.4:c.698A>C or p.(Gln233Pro)].

All 11 individuals presented with a common phenotype consisting of DD/ID (in 9/11 for whom this information was available), cerebellar, ocular and genital anomalies as well as similar facial features.

In total 6 different variants (5 truncating and 1 missense SNV) have been reported. There are no functional studies performed appart from in silico visualisation for the missense variant and protein interaction network analysis for MAB21L1. Previous studies in Mab21l1 knockout mice suggest ocular as well as preputial gland anomalies.

ID appears to be a feature for biallelic mutations in MAB21L2, another member of the male abnormal 21 (MAB21)-like proteins (gene rated green in this panel - associated phenotype : Microphthalmia/coloboma and skeletal dysplasia syndrome, MIM 615877).

MAB21L1 is included in gene panels for intellectual disability offered by some diagnostic laboratoires.

As a result, this gene can be considered for inclusion in this panel as green (or amber)
Sources: Literature, Expert Review
Early onset or syndromic epilepsy v0.1276 RORB Sarah Leigh Mode of inheritance for gene: RORB was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hypophosphataemia or rickets v0.9 ENPP1 Ivone Leong commented on gene: ENPP1: ENPP1 is a green gene on the Skeletal dysplasia panel (Version 1.129).
Hypophosphataemia or rickets v0.9 FGF23 Ivone Leong commented on gene: FGF23: FGF23 is a green gene on the Skeletal dysplasia panel (Version 1.129).
Hypophosphataemia or rickets v0.9 PHEX Ivone Leong commented on gene: PHEX: PHEX is a green gene on the Skeletal dysplasia panel (Version 1.129).
Hypophosphataemia or rickets v0.9 SLC34A3 Ivone Leong commented on gene: SLC34A3: SLC34A3 is a green gene on the Skeletal dysplasia panel (Version 1.129).
Hypophosphataemia or rickets v0.9 FAM20C Ivone Leong reviewed gene: FAM20C: Rating: GREEN; Mode of pathogenicity: None; Publications: 29751744, 17924334, 19250384, 20825432; Phenotypes: ; Mode of inheritance: None
Intellectual disability v2.561 COASY Louise Daugherty Phenotypes for gene: COASY were changed from NEURODEGENERATION WITH BRAIN IRON ACCUMULATION to Neurodegeneration with brain iron accumulation 6, 615643
Ductal plate malformation v1.0 Ellen McDonagh promoted panel to version 1.0
Intellectual disability v2.560 SCAPER Louise Daugherty Classified gene: SCAPER as Green List (high evidence)
Intellectual disability v2.560 SCAPER Louise Daugherty Added comment: Comment on list classification: Changed from Red to Green. Appropriate phenotypes, sufficient cases, and external review comment all support gene-disease association in view of new publication Tatour et al. (2017) PMID: 28794130
Intellectual disability v2.560 SCAPER Louise Daugherty Gene: scaper has been classified as Green List (High Evidence).
Intellectual disability v2.559 SCAPER Louise Daugherty edited their review of gene: SCAPER: Changed rating: GREEN
Ductal plate malformation v0.73 PKD2 Ivone Leong commented on gene: PKD2: There are >3 unrelated families with variants in this gene and it is a green gene on the Rare multisystem ciliopathy disorders (Version 1.78).
Intellectual disability v2.559 SCAPER Louise Daugherty Publications for gene: SCAPER were set to 21937992; 28794130
Ductal plate malformation v0.73 PKD1 Ivone Leong commented on gene: PKD1: There are >3 unrelated families with variants in this gene and it is a green gene on the Rare multisystem ciliopathy disorders (Version 1.78).
Retinal disorders v1.91 SCAPER Louise Daugherty Publications for gene: SCAPER were set to 28041643
Retinal disorders v1.90 SCAPER Louise Daugherty edited their review of gene: SCAPER: Changed rating: GREEN
Ductal plate malformation v0.73 B9D1 Ivone Leong Tag watchlist tag was added to gene: B9D1.
Ductal plate malformation v0.73 KCNN3 Ivone Leong Tag watchlist tag was added to gene: KCNN3.
Retinal disorders v1.90 SCAPER Louise Daugherty Classified gene: SCAPER as Green List (high evidence)
Retinal disorders v1.90 SCAPER Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotypes, sufficient cases, and internal clinical support for gene-disease association. Retinitis pigmentosa onset is variable and spans child / adult onset depending on the gene, so it is fine to be on the retinal panel.
Retinal disorders v1.90 SCAPER Louise Daugherty Gene: scaper has been classified as Green List (High Evidence).
Retinal disorders v1.89 SCAPER Louise Daugherty Mode of inheritance for gene: SCAPER was changed from to BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v1.88 SCAPER Louise Daugherty commented on gene: SCAPER: Past onto internal clinical team for further review and consideration to upgrade rating to Green. Query on Retinitis pigmentosa onset.
Retinal disorders v1.88 SCAPER Louise Daugherty edited their review of gene: SCAPER: Changed rating: AMBER
Early onset or syndromic epilepsy v0.1275 FUCA1 Louise Daugherty Marked gene: FUCA1 as ready
Early onset or syndromic epilepsy v0.1275 FUCA1 Louise Daugherty Gene: fuca1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1275 FRRS1L Louise Daugherty Marked gene: FRRS1L as ready
Early onset or syndromic epilepsy v0.1275 FRRS1L Louise Daugherty Gene: frrs1l has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1275 FOLR1 Louise Daugherty Marked gene: FOLR1 as ready
Early onset or syndromic epilepsy v0.1275 FOLR1 Louise Daugherty Gene: folr1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1275 FKTN Louise Daugherty Marked gene: FKTN as ready
Early onset or syndromic epilepsy v0.1275 FKTN Louise Daugherty Gene: fktn has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1275 FKRP Louise Daugherty Marked gene: FKRP as ready
Early onset or syndromic epilepsy v0.1275 FKRP Louise Daugherty Gene: fkrp has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1275 FKRP Louise Daugherty Publications for gene: FKRP were set to 14652796; 234206531; 11741828; 11592034
Early onset or syndromic epilepsy v0.1274 FKRP Louise Daugherty Added comment: Comment on publications: MDC1C is a form of congenital muscular dystrophy with mental retardation and structural brain abnormalities and belongs to a group of disorders resulting from defective glycosylation of dystrophin-associated glycoprotein-1, collectively known as dystroglycanopathies. External expert review notes Green status, but there is not enough evidence to date to asocaited this gene with seizures so I have kept this gene Amber on this panel until further evidence.
Early onset or syndromic epilepsy v0.1274 FKRP Louise Daugherty Publications for gene: FKRP were set to 14652796
Intellectual disability v2.558 FMR1_CGG Ellen McDonagh Tag currently-ngs-unreportable tag was added to STR: FMR1_CGG.
Intellectual disability v2.558 DOCK6 Konstantinos Varvagiannis reviewed gene: DOCK6: Rating: GREEN; Mode of pathogenicity: None; Publications: 25824905, 27077170; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Intellectual disability v2.558 KMT2B Konstantinos Varvagiannis reviewed gene: KMT2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 29697234; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Early onset or syndromic epilepsy v0.1273 CCDC88A Sarah Leigh Publications for gene: CCDC88A were set to 26917597
Early onset or syndromic epilepsy v0.1272 RORB Sarah Leigh Phenotypes for gene: RORB were changed from to generalized epilepsies with predominant absence seizures
Early onset or syndromic epilepsy v0.1271 RORB Sarah Leigh Publications for gene: RORB were set to
Early onset or syndromic epilepsy v0.1270 ROGDI Sarah Leigh Classified gene: ROGDI as Green List (high evidence)
Early onset or syndromic epilepsy v0.1270 ROGDI Sarah Leigh Gene: rogdi has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1269 ROGDI Sarah Leigh Marked gene: ROGDI as ready
Early onset or syndromic epilepsy v0.1269 ROGDI Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 8 variants reported in at least 7 unrelated cases.
Early onset or syndromic epilepsy v0.1269 ROGDI Sarah Leigh Gene: rogdi has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1269 ROGDI Sarah Leigh Publications for gene: ROGDI were set to
Early onset or syndromic epilepsy v0.1268 ROGDI Sarah Leigh Mode of inheritance for gene: ROGDI was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1267 ROGDI Sarah Leigh Phenotypes for gene: ROGDI were changed from to Kohlschutter-Tonz syndrome 226750
Early onset or syndromic epilepsy v0.1266 RNU4ATAC Sarah Leigh Marked gene: RNU4ATAC as ready
Early onset or syndromic epilepsy v0.1266 RNU4ATAC Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. Three case reported of Microcephalic osteodysplastic primordial dwarfism, type I 210710 ()MOPD1 with seizures as part of their phenotype (PMID 21474761;23794361;22786707) . However, not clear from pmid 23794361 & 22786707 whether the cases were related or not. Thirteen more cases of MOPD1 with RNU4ATAC variants were reported (PMID 29370840, 27591150, 27312855, 26641461, 27040866, 25735804, 22581640), but seizures were not reported in any of these.
Early onset or syndromic epilepsy v0.1266 RNU4ATAC Sarah Leigh Gene: rnu4atac has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1266 FKRP Louise Daugherty Phenotypes for gene: FKRP were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5, 613153; seizures; Walker-warburg syndrome or muscle-eye-brain disease to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5, 613153; seizures; Walker-warburg syndrome or muscle-eye-brain disease; Muscular dystrophy, congenital, 1c
Early onset or syndromic epilepsy v0.1265 FKRP Louise Daugherty Publications for gene: FKRP were set to
Hypophosphataemia or rickets v0.9 CYP2R1 Ivone Leong Mode of inheritance for gene: CYP2R1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Hypophosphataemia or rickets v0.8 CYP2R1 Ivone Leong reviewed gene: CYP2R1: Rating: GREEN; Mode of pathogenicity: None; Publications: 22855339, 15128933, 28548312, 25942481; Phenotypes: ; Mode of inheritance: None
Early onset or syndromic epilepsy v0.1264 RNU4ATAC Sarah Leigh Publications for gene: RNU4ATAC were set to 21474761; 23794361; 22786707
Early onset or syndromic epilepsy v0.1263 RNU4ATAC Sarah Leigh Publications for gene: RNU4ATAC were set to
Early onset or syndromic epilepsy v0.1262 FKRP Louise Daugherty Phenotypes for gene: FKRP were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5, 613153; seizures to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5, 613153; seizures; Walker-warburg syndrome or muscle-eye-brain disease
Early onset or syndromic epilepsy v0.1261 FKRP Louise Daugherty Phenotypes for gene: FKRP were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5, 613153 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5, 613153; seizures
Early onset or syndromic epilepsy v0.1260 FKRP Louise Daugherty Mode of inheritance for gene: FKRP was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1259 FARS2 Rebecca Foulger Marked gene: FARS2 as ready
Early onset or syndromic epilepsy v0.1259 FARS2 Rebecca Foulger Gene: fars2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1259 FARS2 Rebecca Foulger Classified gene: FARS2 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1259 FARS2 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Green review by Zornitza- seizures are a common phentoype of MIM:614946. Plenty of unrelated (>3) cases of seizures in FARS2 patients from the literature (PMIDs 24161539, 22833457, 22499341, 28043061) as summarised in 29126765.
Early onset or syndromic epilepsy v0.1259 FARS2 Rebecca Foulger Gene: fars2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1258 FARS2 Rebecca Foulger commented on gene: FARS2: PMID:22499341 (Shamseldin et al 2012) report an index patient and her two siblings with a homozygous FARS2 variant c.431A>G (p.Y144C). The patients had uncontrolled seizures starting in infancy.
Early onset or syndromic epilepsy v0.1258 FARS2 Rebecca Foulger commented on gene: FARS2: Cho et al, 2017 (PMID:28043061) report a novel homozgyous c.925G>A (G309S) missense variant in FARS2 in 4 patients from 2 nonconsanguineous Korean families. All 4 patients had intractable seizures.
Early onset or syndromic epilepsy v0.1258 FARS2 Rebecca Foulger commented on gene: FARS2: PMID:22833457 (Elo et al 2012) discovered compound het FARS2 variants in two siblings with fatal epileptic mitochondrial encephalopathy (p.I329T and p.D391V).
Early onset or syndromic epilepsy v0.1258 FARS2 Rebecca Foulger commented on gene: FARS2
Early onset or syndromic epilepsy v0.1258 FARS2 Rebecca Foulger Publications for gene: FARS2 were set to 24161539, 22833457, 22499341, 29126765
Early onset or syndromic epilepsy v0.1257 FARS2 Rebecca Foulger Publications for gene: FARS2 were set to
Early onset or syndromic epilepsy v0.1256 FARS2 Rebecca Foulger Mode of inheritance for gene: FARS2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1255 FARS2 Rebecca Foulger Phenotypes for gene: FARS2 were changed from to Combined oxidative phosphorylation deficiency 14, 614946
Limb disorders v0.276 PROM1 Eleanor Williams Marked gene: PROM1 as ready
Limb disorders v0.276 PROM1 Eleanor Williams Added comment: Comment when marking as ready: No evidence that this gene is associated with a limb phenotype.
Limb disorders v0.276 PROM1 Eleanor Williams Gene: prom1 has been classified as Red List (Low Evidence).
Limb disorders v0.276 PROM1 Eleanor Williams commented on gene: PROM1
Limb disorders v0.276 PNPLA6 Eleanor Williams Marked gene: PNPLA6 as ready
Limb disorders v0.276 PNPLA6 Eleanor Williams Added comment: Comment when marking as ready: No evidence that this gene is associated with limb disorders.
Limb disorders v0.276 PNPLA6 Eleanor Williams Gene: pnpla6 has been classified as Red List (Low Evidence).
Limb disorders v0.276 PNPLA6 Eleanor Williams commented on gene: PNPLA6
Hypophosphataemia or rickets v0.8 VDR Ivone Leong edited their review of gene: VDR: Changed rating: GREEN
Hypophosphataemia or rickets v0.8 CYP27B1 Ivone Leong edited their review of gene: CYP27B1: Changed rating: GREEN
Early onset or syndromic epilepsy v0.1254 EXOSC3 Rebecca Foulger commented on gene: EXOSC3: PMID:24524299 (Eggens et al, 2014) summarise 14 patients with the EXOSC3 variants out of a cohort of 99 PCH patients (90 families). Seizures are reported in patients 7-I and Patient 8. Seizures were not recorded in the p.G31A group (6 patients, 5 families).
Early onset or syndromic epilepsy v0.1254 EXOSC3 Rebecca Foulger commented on gene: EXOSC3: PMID:23883322: states that Epileptic seizures were not noted in any of their patients.
Early onset or syndromic epilepsy v0.1254 EXOSC3 Rebecca Foulger Publications for gene: EXOSC3 were set to
Early onset or syndromic epilepsy v0.1253 EXOSC3 Rebecca Foulger commented on gene: EXOSC3: PMID:25144110 summary confirms that epileptic seizures are reported in some patients.
Early onset or syndromic epilepsy v0.1253 EXOSC3 Rebecca Foulger commented on gene: EXOSC3: PMID:25149867 (Halevy et al, 2014): Of the 4 patients, 1 patient had a single atonic seizure age 12 years.
Early onset or syndromic epilepsy v0.1253 EXOSC3 Rebecca Foulger commented on gene: EXOSC3
Intellectual disability v2.558 ODC1 Konstantinos Varvagiannis gene: ODC1 was added
gene: ODC1 was added to Intellectual disability. Sources: Literature,Expert Review
Mode of inheritance for gene: ODC1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ODC1 were set to 30239107; 30475435
Phenotypes for gene: ODC1 were set to Global developmental delay; Intellectual disability; Macrocephaly; Alopecia; Ectodermal dysplasia
Penetrance for gene: ODC1 were set to unknown
Review for gene: ODC1 was set to GREEN
Added comment: PMIDs 30239107 and 30475435 report on 5 cases of de novo truncating ODC1 variants in unrelated families. One concerned a stillborn male. The 4 remaining individuals presented with a similar phenotype consisting of alopecia and other ectodermal anomalies, DD/ID, relative or absolute macrocephaly and common facial features. DD/ID was severe in some instances and many of these individuals had extensive prior testing for other disorders (Fragile-X, PTEN, SLC2A1, chromosomal disorders, etc).

ODC1 (ornithine decarboxylase 1) converts enzymatically ornithine to putrescine. All variants reported to date are truncating but lead to gain-of-function. Specifically they affect a 37 amino acid c-terminal destabilization region critical for the degradation of ODC1 and - as a result - lead to increased levels of ODC1 as well as putrescine.

A mouse model with identical phenotype has been described several years ago.

The role of ODC inhibitors is extensively discussed in both publications.

As a result, ODC1 can be considered for inclusion in the ID panel as green (or amber).
Sources: Literature, Expert Review
Early onset or syndromic epilepsy v0.1253 NSD1 Ivone Leong Marked gene: NSD1 as ready
Early onset or syndromic epilepsy v0.1253 NSD1 Ivone Leong Gene: nsd1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1253 RNU4ATAC Sarah Leigh Mode of inheritance for gene: RNU4ATAC was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1252 RNU4ATAC Sarah Leigh Phenotypes for gene: RNU4ATAC were changed from to Microcephalic osteodysplastic primordial dwarfism, type I 210710
Early onset or syndromic epilepsy v0.1251 RNASET2 Sarah Leigh Marked gene: RNASET2 as ready
Early onset or syndromic epilepsy v0.1251 RNASET2 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 6 variants reported in 5 unrelated cases, seizures were a phenotypic feature in 4 cases. Supportive functional studies were also presented (PMID 19525954).
Early onset or syndromic epilepsy v0.1251 RNASET2 Sarah Leigh Gene: rnaset2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1251 RNASET2 Sarah Leigh Classified gene: RNASET2 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1251 RNASET2 Sarah Leigh Gene: rnaset2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1250 FKTN Louise Daugherty Classified gene: FKTN as Green List (high evidence)
Early onset or syndromic epilepsy v0.1250 FKTN Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotypes, sufficient cases, and external review comment all support gene-disease association
Early onset or syndromic epilepsy v0.1250 FKTN Louise Daugherty Gene: fktn has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1249 FKTN Louise Daugherty Added comment: Comment on publications: added publication to support gene-disease association
Early onset or syndromic epilepsy v0.1249 FKTN Louise Daugherty Publications for gene: FKTN were set to 30220444; 9690476
Early onset or syndromic epilepsy v0.1248 FKTN Louise Daugherty Phenotypes for gene: FKTN were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4, 253800; seizures to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4, 253800; seizures; Walker-warburg syndrome or muscle-eye-brain disease; Fukuyama congenital muscular dystrophy
Early onset or syndromic epilepsy v0.1247 RNASET2 Sarah Leigh Mode of inheritance for gene: RNASET2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1246 RNASET2 Sarah Leigh Publications for gene: RNASET2 were set to
Early onset or syndromic epilepsy v0.1245 RNASET2 Sarah Leigh Phenotypes for gene: RNASET2 were changed from to Leukoencephalopathy, cystic, without megalencephaly 612951
Early onset or syndromic epilepsy v0.1244 FKTN Louise Daugherty Publications for gene: FKTN were set to
Early onset or syndromic epilepsy v0.1243 NSD1 Ivone Leong Classified gene: NSD1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1243 NSD1 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. NSD1 is confirmed to be associated with Sotos syndrome on OMIM and Gene2Phenotype, and both databases have listed seizures as a phenotype. GeneReviews stated that ~25% of Sotos syndrome patients have seizures. A large multicentre gene-phenotype association study showed that there are multiple cases (>3) of Sotos syndrome patients who have seizures.
Early onset or syndromic epilepsy v0.1243 NSD1 Ivone Leong Gene: nsd1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1242 NSD1 Ivone Leong Publications for gene: NSD1 were set to
Early onset or syndromic epilepsy v0.1241 EXOSC3 Rebecca Foulger Mode of inheritance for gene: EXOSC3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1240 FKTN Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Early onset or syndromic epilepsy v0.1240 FKTN Louise Daugherty Phenotypes for gene: FKTN were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4, 253800; seizures
Early onset or syndromic epilepsy v0.1239 FKTN Louise Daugherty Added comment: Comment on mode of inheritance: Added MOI from external clinical review and publications
Early onset or syndromic epilepsy v0.1239 FKTN Louise Daugherty Mode of inheritance for gene: FKTN was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1238 FOLR1 Louise Daugherty Classified gene: FOLR1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1238 FOLR1 Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotypes, sufficient cases, and external review comment all support gene-disease association.
Early onset or syndromic epilepsy v0.1238 FOLR1 Louise Daugherty Gene: folr1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1237 FOLR1 Louise Daugherty Added comment: Comment on publications: Added publications to support gene-disease association, and upgrading of the gene to Green
Early onset or syndromic epilepsy v0.1237 FOLR1 Louise Daugherty Publications for gene: FOLR1 were set to
Early onset or syndromic epilepsy v0.1236 FOLR1 Louise Daugherty Added comment: Comment on mode of inheritance: Added MOI from external clinical review and publications
Early onset or syndromic epilepsy v0.1236 FOLR1 Louise Daugherty Mode of inheritance for gene: FOLR1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1235 FOLR1 Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Early onset or syndromic epilepsy v0.1235 FOLR1 Louise Daugherty Phenotypes for gene: FOLR1 were changed from to Neurodegeneration due to cerebral folate transport deficiency, 613068; seizures
Early onset or syndromic epilepsy v0.1234 FRRS1L Louise Daugherty Classified gene: FRRS1L as Green List (high evidence)
Early onset or syndromic epilepsy v0.1234 FRRS1L Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotypes, sufficient cases, and external review comment all support gene-disease association.
Early onset or syndromic epilepsy v0.1234 FRRS1L Louise Daugherty Gene: frrs1l has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1233 FRRS1L Louise Daugherty Added comment: Comment on publications: Added publications suggested from external expert review to support upgrading of the gene to Green
Early onset or syndromic epilepsy v0.1233 FRRS1L Louise Daugherty Publications for gene: FRRS1L were set to
Early onset or syndromic epilepsy v0.1232 NSD1 Ivone Leong Mode of inheritance for gene: NSD1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v0.1231 FRRS1L Louise Daugherty Added comment: Comment on mode of inheritance: Added MOI from external clinical review and publications
Early onset or syndromic epilepsy v0.1231 FRRS1L Louise Daugherty Mode of inheritance for gene: FRRS1L was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1230 FRRS1L Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Early onset or syndromic epilepsy v0.1230 FRRS1L Louise Daugherty Phenotypes for gene: FRRS1L were changed from to Epileptic encephalopathy, early infantile 37, 616981
Early onset or syndromic epilepsy v0.1229 FUCA1 Louise Daugherty Classified gene: FUCA1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1229 FUCA1 Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotypes, sufficient cases, and external review comment all support gene-disease association.
Early onset or syndromic epilepsy v0.1229 FUCA1 Louise Daugherty Gene: fuca1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1228 FUCA1 Louise Daugherty Added comment: Comment on publications: added publication to support gene-disease association
Early onset or syndromic epilepsy v0.1228 FUCA1 Louise Daugherty Publications for gene: FUCA1 were set to
Early onset or syndromic epilepsy v0.1227 EXOSC3 Rebecca Foulger Phenotypes for gene: EXOSC3 were changed from to Pontocerebellar hypoplasia, type 1B, 614678
Early onset or syndromic epilepsy v0.1226 ETHE1 Rebecca Foulger Classified gene: ETHE1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1226 ETHE1 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Green review by Zornitza. Confirmed DD-G2P gene for Ethylmalonic encephalopathy (EE) which can present with seizures. Sufficient cases of patients with EE and seizures for inclusion on panel (as summarised by PMID:26194623).
Early onset or syndromic epilepsy v0.1226 ETHE1 Rebecca Foulger Gene: ethe1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1225 ETHE1 Rebecca Foulger Marked gene: ETHE1 as ready
Early onset or syndromic epilepsy v0.1225 ETHE1 Rebecca Foulger Gene: ethe1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1225 ETHE1 Rebecca Foulger commented on gene: ETHE1: PMID:26194623 (Papetti et al 2015) report on a baby with severe early onset EE associated with a novel ETHE1 gene variant and a an early pure epileptic onset. They also provide a summary of all previous EE cases. A large proportion report seizures- although the earlier cases don't report a ETHE1 gene defect, there are sufficient cases with both seizures and an ETHE1 variant reported.
Early onset or syndromic epilepsy v0.1225 ETHE1 Rebecca Foulger commented on gene: ETHE1
Early onset or syndromic epilepsy v0.1225 NSD1 Ivone Leong Phenotypes for gene: NSD1 were changed from to Sotos syndrome 1, 117550
Early onset or syndromic epilepsy v0.1224 NPRL3 Ivone Leong Marked gene: NPRL3 as ready
Early onset or syndromic epilepsy v0.1224 NPRL3 Ivone Leong Gene: nprl3 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1224 NPRL3 Ivone Leong Classified gene: NPRL3 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1224 NPRL3 Ivone Leong Added comment: Comment on list classification: NPRL3 is confirmed to be associated with Epilepsy, familial focal on OMIM but not on Gene2Phenotype. There are >3 cases (PMID: 26505888; 26285051; 27173016) of patients from unrelated families who have familial focal epilepsy with variants in NPRL3.
Early onset or syndromic epilepsy v0.1224 NPRL3 Ivone Leong Gene: nprl3 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1223 ETHE1 Rebecca Foulger Mode of inheritance for gene: ETHE1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1222 ETHE1 Rebecca Foulger Phenotypes for gene: ETHE1 were changed from to Ethylmalonic encephalopathy, 602473
Early onset or syndromic epilepsy v0.1221 EMX2 Rebecca Foulger Marked gene: EMX2 as ready
Early onset or syndromic epilepsy v0.1221 EMX2 Rebecca Foulger Gene: emx2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1221 EMX2 Rebecca Foulger Classified gene: EMX2 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1221 EMX2 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Green review by Zornitza and 3 cases of Schizencephaly patients with EMX2 variants and partial epilepsy in PMID:9359037. PMID:15921232 (2005) report that half of Schizencephaly patients show epilepsy. Therefore sufficient evidence for inclusion on panel.
Early onset or syndromic epilepsy v0.1221 EMX2 Rebecca Foulger Gene: emx2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1220 EMX2 Rebecca Foulger commented on gene: EMX2: Faiella et al., 1997 (PMID:9359037) summarise 10 patients with Schizencephaly. 6 patients were heterozygous for de novo variants in EMX2 (including 2 brothers). 3 of these unrelated patients have EMX2 variants (patients VF, MB and PB).
Early onset or syndromic epilepsy v0.1220 EMX2 Rebecca Foulger Added comment: Comment on mode of inheritance: Monoallelic MOI supported by Gene2Phenotype, which provide a 'possible' rating for Familial Schizencephaly.
Early onset or syndromic epilepsy v0.1220 EMX2 Rebecca Foulger Mode of inheritance for gene: EMX2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v0.1219 NPRL3 Ivone Leong Added comment: Comment on mode of inheritance: Incomplete penetrance was observed in some of the studies (PMID: 265005888,26285051).
Early onset or syndromic epilepsy v0.1219 NPRL3 Ivone Leong Mode of inheritance for gene: NPRL3 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v0.1218 EMX2 Rebecca Foulger commented on gene: EMX2
Early onset or syndromic epilepsy v0.1218 EMX2 Rebecca Foulger Publications for gene: EMX2 were set to
Early onset or syndromic epilepsy v0.1217 EMX2 Rebecca Foulger commented on gene: EMX2
Early onset or syndromic epilepsy v0.1217 NPRL3 Ivone Leong Publications for gene: NPRL3 were set to
Early onset or syndromic epilepsy v0.1216 EMX2 Rebecca Foulger Phenotypes for gene: EMX2 were changed from to Schizencephaly, 269160
Early onset or syndromic epilepsy v0.1215 EIF2S3 Rebecca Foulger Marked gene: EIF2S3 as ready
Early onset or syndromic epilepsy v0.1215 EIF2S3 Rebecca Foulger Gene: eif2s3 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1215 EIF2S3 Rebecca Foulger Classified gene: EIF2S3 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1215 EIF2S3 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Probable rating in Gene2Phenotype for 'Syndromic ID with severe microcephaly' but sufficient unrelated cases (>3) of seizures in MEHMO patients from literature (PMIDs 23063529,27333055,28055140).
Early onset or syndromic epilepsy v0.1215 EIF2S3 Rebecca Foulger Gene: eif2s3 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1214 EIF2S3 Rebecca Foulger Added comment: Comment on mode of inheritance: X-linked recessive MOI supported by OMIM and literature.
Early onset or syndromic epilepsy v0.1214 EIF2S3 Rebecca Foulger Mode of inheritance for gene: EIF2S3 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early onset or syndromic epilepsy v0.1213 EIF2S3 Rebecca Foulger Publications for gene: EIF2S3 were set to
Early onset or syndromic epilepsy v0.1212 EIF2S3 Rebecca Foulger commented on gene: EIF2S3: Skopkova et al 2017 (PMID:28055140) identified a C-terminal frameshift mutation (Ile465Serfs) in the EIF2S3 gene in three families with MEHMO syndrome and a novel maternally inherited missense EIF2S3 variant (c.324T>A; p.Ser108Arg) in another male patient with less severe clinical symptoms. Two of the families had members with seizures amongst their phenotypes.
Early onset or syndromic epilepsy v0.1212 EIF2S3 Rebecca Foulger commented on gene: EIF2S3: Moortgat et al, 2016 (PMID:27333055) examined syndromic intellectual disability in two unrelated families with suspected X-linked inheritance. In both families, affected males presented with severe intellectual disability, microcephaly, growth retardation, and epilepsy in most individuals. A missense variant(c.777T>G p.(Ile259Met)) and a frameshift variant (c.1394_1397del p.(Ile465Serfs*4)) were identified in the EIF2S3 gene in the hemizygous state in affected patients, and in the heterozygous states female obligate carriers.
Early onset or syndromic epilepsy v0.1212 EIF2S3 Rebecca Foulger commented on gene: EIF2S3: Borck et al., 2012 (PMID:23063529) ascertained a family of Morocco Jewish ancestry in which three male individuals were affected by X-linked intellectual disability (ID). Individual III:2 had generalized seizures.
Early onset or syndromic epilepsy v0.1212 EIF2S3 Rebecca Foulger commented on gene: EIF2S3
Early onset or syndromic epilepsy v0.1212 NPRL3 Ivone Leong Phenotypes for gene: NPRL3 were changed from to Epilepsy, familial focal, with variable foci 3, 617118
Early onset or syndromic epilepsy v0.1211 EIF2S3 Rebecca Foulger Phenotypes for gene: EIF2S3 were changed from to MEHMO syndrome, 300148
Intellectual disability v2.558 FBXL3 Konstantinos Varvagiannis gene: FBXL3 was added
gene: FBXL3 was added to Intellectual disability. Sources: Literature,Expert Review
Mode of inheritance for gene: FBXL3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FBXL3 were set to 30481285
Phenotypes for gene: FBXL3 were set to Intellectual disability; Short stature
Penetrance for gene: FBXL3 were set to Complete
Review for gene: FBXL3 was set to GREEN
Added comment: Ansar et al. (PMID: 30481285) report on 8 individuals from 3 consanguineous families, all homozygous for FBXL3 variants.

The phenotype consisted of mild to severe intellectual disability (8/8), short stature (8/8) with a few common facial features.

In the first family - from Pakistan - all affected individuals were homozygous for a frameshift variant. The 2 sibs from the second family (from Lebanon) were homozygous for a nonsense variant. A further patient, born to distantly related parents from Italy, was found to harbor a missense variant [NM_012158.2:c.1072T>C or p.(Cys358Arg)] in the homozygous state.

FBXL3 is part of an ubiquitin ligase complex that binds the central clock protein cryptochromes (CRY1/2) mediating their degradation. Cys358Arg concerns the same codon as a similar - previously studied - variant (Cys358Ser) reported to affect the mouse circadian rhythm. Disturbance of circadian rhythm was observed in the patient with the Cys358Arg variant.

As previously demonstrated for mutations of the same codon and in line with a pathogenic role for this variant, in silico studies predict impaired interaction of FBXL3 with CRY2. It is proposed that the nonsense and frameshift variants lead to a similar effect due to severe truncation of the protein (upstream of leucine-rich domains important for this interaction).

The authors note that other F-box proteins are implicated in intellectual disability (as in the case of FBXO11 and FBXL4, both rated green in this panel).

As a result, FBXL3 can be considered for inclusion in this panel as green (or amber).
Sources: Literature, Expert Review
Early onset or syndromic epilepsy v0.1210 FUCA1 Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Early onset or syndromic epilepsy v0.1210 FUCA1 Louise Daugherty Phenotypes for gene: FUCA1 were changed from to Fucosidosis, 230000; seizures
Early onset or syndromic epilepsy v0.1209 FUCA1 Louise Daugherty Added comment: Comment on mode of inheritance: changed MOI from external clinical review and publications
Early onset or syndromic epilepsy v0.1209 FUCA1 Louise Daugherty Mode of inheritance for gene: FUCA1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v2.558 FUCA1 Louise Daugherty Phenotypes for gene: FUCA1 were changed from Fucosidosis, 230000; FUCOSIDOSIS (FUCA1D) to Fucosidosis, 230000; FUCOSIDOSIS (FUCA1D); intellectual disability
Intellectual disability v2.557 FUCA1 Louise Daugherty Publications for gene: FUCA1 were set to
Hypophosphataemia or rickets v0.8 CLCN5 Ivone Leong reviewed gene: CLCN5: Rating: ; Mode of pathogenicity: None; Publications: 28383812, 9187673; Phenotypes: ; Mode of inheritance: None
Hypophosphataemia or rickets v0.8 VDR Ivone Leong commented on gene: VDR
Hypophosphataemia or rickets v0.8 CYP27B1 Ivone Leong commented on gene: CYP27B1: CYP27B1 is a green gene on the Skeletal dysplasia panel.
Hypophosphataemia or rickets v0.8 CYP27B1 Ivone Leong reviewed gene: CYP27B1: Rating: ; Mode of pathogenicity: None; Publications: 9486994, 9415400; Phenotypes: ; Mode of inheritance: None
Hypophosphataemia or rickets v0.8 SLC34A3 Ivone Leong Marked gene: SLC34A3 as ready
Hypophosphataemia or rickets v0.8 SLC34A3 Ivone Leong Added comment: Comment when marking as ready: OMIM lists hypophosphataemic rickets as a phenotype associated with SLC34A3; however, nothing is listed on Gene2Phenotype. There are more then 3 families with hypophosphataemic rickets with different SLC34A3 variants.
Hypophosphataemia or rickets v0.8 SLC34A3 Ivone Leong Gene: slc34a3 has been classified as Green List (High Evidence).
Hypophosphataemia or rickets v0.8 SLC34A3 Ivone Leong Publications for gene: SLC34A3 were set to
Hypophosphataemia or rickets v0.7 ENPP1 Ivone Leong Marked gene: ENPP1 as ready
Hypophosphataemia or rickets v0.7 ENPP1 Ivone Leong Added comment: Comment when marking as ready: Both OMIM and Gene2Phenotype confirm that ENPP1 is associated with autosomal recessive hypophosphataemic rickets (ARHR). One study (PMID: 20137773) describes 5 individuals with ARHR from 4 unrelated families. The study found 3 different ENPP1 variants. Another study (PMID: 20137772) reported on two brothers with ARHR who have homozygous ENPP1 variant.
Hypophosphataemia or rickets v0.7 ENPP1 Ivone Leong Gene: enpp1 has been classified as Green List (High Evidence).
Hypophosphataemia or rickets v0.7 ENPP1 Ivone Leong Publications for gene: ENPP1 were set to
Hypophosphataemia or rickets v0.6 DMP1 Ivone Leong Marked gene: DMP1 as ready
Hypophosphataemia or rickets v0.6 DMP1 Ivone Leong Added comment: Comment when marking as ready: Hypophosphataemic rickets confirmed on OMIM and Gene2Phenotype as associated with DMP1. DMP1 is a green gene on the Skeletal dysplasia panel. One study reported 3 unrelated families with affected members diagnosed with hypophosphataemic rickets who have DMP1 variants (PMID: 17033625). Another 2 studies reported 2 patients with variants in DMP1 diagnosed with hypophosphataemic rickets (PMID: 22695891,20213538). There is also a mouse model (PMID:15590631) to further support his association.
Hypophosphataemia or rickets v0.6 DMP1 Ivone Leong Gene: dmp1 has been classified as Green List (High Evidence).
Hypophosphataemia or rickets v0.6 DMP1 Ivone Leong Publications for gene: DMP1 were set to
Hypophosphataemia or rickets v0.5 FGF23 Ivone Leong Marked gene: FGF23 as ready
Hypophosphataemia or rickets v0.5 FGF23 Ivone Leong Added comment: Comment when marking as ready: Autosomal dominant hypophosphataemic rickets (ADHR) is confirmed to be associated with FGF23 on OMIM but not Gene2Phenotype. It is a green gene on the Skeletal hyperplasia panel. There is one family reported with a variant in FGF23 diagnosed with ADHR (PMID: 28383812). Another study reported two different variants in FgF23 in two unrelated families diagnosed with ADHR (PMID:11062477). Mouse model with conditional deletion of FGF23 (PMID: 26792657) further supports that variants in FGF23 cause ADHR.
Hypophosphataemia or rickets v0.5 FGF23 Ivone Leong Gene: fgf23 has been classified as Green List (High Evidence).
Hypophosphataemia or rickets v0.5 FGF23 Ivone Leong Publications for gene: FGF23 were set to
Hypophosphataemia or rickets v0.4 PHEX Ivone Leong Marked gene: PHEX as ready
Hypophosphataemia or rickets v0.4 PHEX Ivone Leong Added comment: Comment when marking as ready: OMIM has confirmed that PHEX is associated with hypophosphataemic rickets; however, no phenotype is listed wih PHEX on Gene2Phenotype. There are many publications linking varaints in PHEX as the cause for hypophosphataemic rickets. Also, based on the review by Sian Ellard (University of Exeter Medical School).
Hypophosphataemia or rickets v0.4 PHEX Ivone Leong Gene: phex has been classified as Green List (High Evidence).
Hypophosphataemia or rickets v0.4 PHEX Ivone Leong Publications for gene: PHEX were set to
Early onset or syndromic epilepsy v0.1208 NDUFAF2 Ivone Leong Marked gene: NDUFAF2 as ready
Early onset or syndromic epilepsy v0.1208 NDUFAF2 Ivone Leong Gene: ndufaf2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1208 NDUFAF2 Ivone Leong Classified gene: NDUFAF2 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1208 NDUFAF2 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. NDUFAF2 is confirmed to be associated with complex I deficiency on OMIM and listed as a probable causative gene on Gene2Phenotype. Both websites list seizures as a phenotype of the disease.
There are reports (PMID: 18180188, 26795593, 22644603) of 3 unrelated patients diagnosed with Leigh syndrome or mitochondrial complex I deficiency with different NDUFAF2 variants who have seizures.
Early onset or syndromic epilepsy v0.1208 NDUFAF2 Ivone Leong Gene: ndufaf2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1207 NDUFAF2 Ivone Leong Publications for gene: NDUFAF2 were set to
Early onset or syndromic epilepsy v0.1206 NDUFAF2 Ivone Leong Mode of inheritance for gene: NDUFAF2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary spastic paraplegia v1.71 HACE1 Chris Buxton gene: HACE1 was added
gene: HACE1 was added to Hereditary spastic paraplegia. Sources: Literature
Mode of inheritance for gene: HACE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HACE1 were set to 26424145; 26437029
Phenotypes for gene: HACE1 were set to Spastic paraplegia; psychomotor retardation; seizure
Penetrance for gene: HACE1 were set to unknown
Review for gene: HACE1 was set to AMBER
Added comment: Associated with 'Spastic paraplegia and psychomotor retardation with or without seizures' is an autosomal recessive complex neurodevelopmental disorder with onset in infancy

Hollstein (2015, 26424145): Exome study, 2 families with 8 affected individuals with biallelic LoF variants. Absence of expressed protein shown by Western blots.

Akawi (2015, 26437029) 6 patients from 4 unrelated families with SPPRS (truncal hypotonia and mixed spastic and dystonic tetraparesis)
Sources: Literature
Hereditary spastic paraplegia v1.71 DARS Chris Buxton gene: DARS was added
gene: DARS was added to Hereditary spastic paraplegia. Sources: Literature
Mode of inheritance for gene: DARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DARS were set to 23643384; 25527264
Phenotypes for gene: DARS were set to Brain stem and spinal cord Hypomyelination; leg spasticity
Penetrance for gene: DARS were set to unknown
Review for gene: DARS was set to AMBER
Added comment: HGMD: 15 missense, 1 ins associated with: Hypomyelination with brain stem and spinal cord involvement and leg spasticity:
An autosomal recessive leukoencephalopathy characterized by onset in the first year of life of severe spasticity, mainly affecting the lower limbs and resulting in an inability to achieve independent ambulation
Taft (2013, 23643384) identiofied compound-heterozygous and homozygous DARS missense variants in 7 unrelated families with severe lower limb spasticity associated with leukoencephalopathy
Phenotype expanded by Wolf (2015, 25527264) to later onset and subacute spastic paraplegia.
Sources: Literature
Ductal plate malformation v0.73 OFD1 Ivone Leong commented on gene: OFD1
Ductal plate malformation v0.73 NPHP3 Ivone Leong commented on gene: NPHP3
Hereditary spastic paraplegia v1.71 ATP13A2 Chris Buxton gene: ATP13A2 was added
gene: ATP13A2 was added to Hereditary spastic paraplegia. Sources: Literature
Mode of inheritance for gene: ATP13A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP13A2 were set to 28137957
Phenotypes for gene: ATP13A2 were set to Adult-onset lower-limb predominant spastic paraparesis
Penetrance for gene: ATP13A2 were set to unknown
Review for gene: ATP13A2 was set to RED
Added comment: Estrada-Cuzcano (2017, 28137957). Biallelic LoF varaints cause complicated hereditary spastic paraplegia.
Exome study identified biallelic missense . Further analysis of 795 HSP /erlated disorders identified 2 families with truncating ATP13A2 variants. Some supportive functional studies.
Clin: Adult-onset lower-limb predominant spastic paraparesis
Sources: Literature
Hereditary spastic paraplegia v1.71 SLC2A1 Chris Buxton gene: SLC2A1 was added
gene: SLC2A1 was added to Hereditary spastic paraplegia. Sources: Literature
Mode of inheritance for gene: SLC2A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC2A1 were set to 11136715; 21832227; 18606970
Phenotypes for gene: SLC2A1 were set to Developmental delay; seizure; paroxysmal choreoathetosis; spastic paraplegia
Penetrance for gene: SLC2A1 were set to unknown
Review for gene: SLC2A1 was set to RED
Added comment: Spastic diplegia described as a component phenotype with a more complex presentation
Klepper (2001, 11136715) described diplegic spasticity associated with other dev delay and seizure phenotype in sibs with a het GLUT1 variant. Weber (2011, 21832227) desribed childhood onset paroxysmal choreoathetosis and progressive spastic paraplegia and het varaints in SLC2A1.
Zorzi (2008, 18606970) described a 22yo Italian woman with het denovo missense in SLC2A1 with delayed psychomotor development, mild mental retardation, microcephaly, dysarthria, and spasticity.
Diagnostic on Sheffield HSP panel.
Sources: Literature
Ductal plate malformation v0.73 ALG8 Ivone Leong Added comment: Comment on mode of inheritance: Changed to monoallelic as variants in ALG8 that cause polycystic liver disease have an autosomal dominant mode of inheritance. Variants in ALG8 has a recessive mode of inheritance when involved with Congenital disorder of glycosylation.
Ductal plate malformation v0.73 ALG8 Ivone Leong Mode of inheritance for gene: ALG8 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary spastic paraplegia v1.71 RAB3GAP2 Chris Buxton gene: RAB3GAP2 was added
gene: RAB3GAP2 was added to Hereditary spastic paraplegia. Sources: Literature
Mode of inheritance for gene: RAB3GAP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RAB3GAP2 were set to 24482476
Phenotypes for gene: RAB3GAP2 were set to spastic paraplegia
Penetrance for gene: RAB3GAP2 were set to unknown
Review for gene: RAB3GAP2 was set to RED
Added comment: Described as a candidate HSP gene: Novarino (2014, 24482476)
single account. Diagnostic on Sheffield HSP panel.
Sources: Literature
Hereditary spastic paraplegia v1.71 LYST Chris Buxton gene: LYST was added
gene: LYST was added to Hereditary spastic paraplegia. Sources: Literature
Mode of inheritance for gene: LYST was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LYST were set to 24521565
Phenotypes for gene: LYST were set to spastic paraplegia
Penetrance for gene: LYST were set to unknown
Added comment: Shimazaki (2014, 24521565), homozygous LYST (c.4189T>G, p.F1397V).
Gene predominantly associated with Chediak-Higashi syndrome. one publication describing a HSP like phenotype.
Diagnostic on Sheffield HSP panel
Sources: Literature
Early onset or syndromic epilepsy v0.1205 EIF2B5 Rebecca Foulger Publications for gene: EIF2B5 were set to 17646634; 21484434; 15136690; 29995139; 18266750
Early onset or syndromic epilepsy v0.1204 EIF2B3 Rebecca Foulger Publications for gene: EIF2B3 were set to
Early onset or syndromic epilepsy v0.1203 EIF2B3 Rebecca Foulger commented on gene: EIF2B3
Early onset or syndromic epilepsy v0.1203 EIF2B3 Rebecca Foulger Phenotypes for gene: EIF2B3 were changed from to Leukoencephalopathy with vanishing white matter, 603896
Early onset or syndromic epilepsy v0.1202 EIF2B3 Rebecca Foulger Mode of inheritance for gene: EIF2B3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1201 EIF2B4 Rebecca Foulger Marked gene: EIF2B4 as ready
Early onset or syndromic epilepsy v0.1201 EIF2B4 Rebecca Foulger Gene: eif2b4 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1201 EIF2B4 Rebecca Foulger Classified gene: EIF2B4 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1201 EIF2B4 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Green review by Zornitza, and sufficient cases of epilepsy in Vanishing White Matter (VWM) patients with EIF2B4 variants from the literature (3 cases in PMIDs 25843247, 26043506 and 29331873) for inclusion on the panel.
Early onset or syndromic epilepsy v0.1201 EIF2B4 Rebecca Foulger Gene: eif2b4 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1200 EIF2B4 Rebecca Foulger Publications for gene: EIF2B4 were set to 25843247; 26043506
Early onset or syndromic epilepsy v0.1199 EIF2B4 Rebecca Foulger commented on gene: EIF2B4: Herrera-García et al, 2018 (PMID:29331873) describe a 41-year-old woman and her 37-year-old sister who developed epilepsy in association with premature ovarian failure at the age of 13 and 18 respectively. In both patients they found the c.1117C>T (p.Arg373Cys) homozygous variant in EIF2B4.
Early onset or syndromic epilepsy v0.1199 EIF2B4 Rebecca Foulger Phenotypes for gene: EIF2B4 were changed from to Leukoencephalopathy with vanishing white matter, 603896
Early onset or syndromic epilepsy v0.1198 EIF2B4 Rebecca Foulger Publications for gene: EIF2B4 were set to 25843247
Early onset or syndromic epilepsy v0.1197 EIF2B4 Rebecca Foulger commented on gene: EIF2B4: Gungor et al (PMID:26043506) report a 12-month old boy presented with intractable seizures present since 3-months of age. A homozygous c.1091G>A variant was detected in the EIF2B4 gene.
Early onset or syndromic epilepsy v0.1197 EIF2B2 Rebecca Foulger Publications for gene: EIF2B2 were set to
Early onset or syndromic epilepsy v0.1196 EIF2B4 Rebecca Foulger Mode of inheritance for gene: EIF2B4 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1195 EIF2B4 Rebecca Foulger Publications for gene: EIF2B4 were set to
Early onset or syndromic epilepsy v0.1194 EIF2B4 Rebecca Foulger commented on gene: EIF2B4
Early onset or syndromic epilepsy v0.1194 EIF2B2 Rebecca Foulger Marked gene: EIF2B2 as ready
Early onset or syndromic epilepsy v0.1194 EIF2B2 Rebecca Foulger Gene: eif2b2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1194 EIF2B2 Rebecca Foulger Classified gene: EIF2B2 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1194 EIF2B2 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Green review from Zornitza. Seizures are seen in some patients with Vanishing White Matter Disease (VWM). Sufficient cases of seizures in patients from the literature (2 in PMID:25843247 and 1 in PMID:22678813) for inclusion on the panel.
Early onset or syndromic epilepsy v0.1194 EIF2B2 Rebecca Foulger Gene: eif2b2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1193 EIF2B2 Rebecca Foulger commented on gene: EIF2B2: Shimada et al, 2012 (PMID:22678813) report an 11-month-old patient with intractable epilepsy amongst her symptoms. A Submicroscopic deletion at 14q24.3 that included EIF2B2 was found in compound heterozygous state for a missense variant in EIF2B2 (V85W). The p.V85E variant may be common in individuals of E. Asian origin (Chinese and Japanese).
Early onset or syndromic epilepsy v0.1193 EIF2B2 Rebecca Foulger commented on gene: EIF2B2
Early onset or syndromic epilepsy v0.1193 EIF2B2 Rebecca Foulger Mode of inheritance for gene: EIF2B2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1192 EIF2B2 Rebecca Foulger Phenotypes for gene: EIF2B2 were changed from to Leukoencephalopathy with vanishing white matter, 603896
Hereditary spastic paraplegia v1.71 KLC4 Chris Buxton gene: KLC4 was added
gene: KLC4 was added to Hereditary spastic paraplegia. Sources: Literature
Mode of inheritance for gene: KLC4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KLC4 were set to 26423925
Phenotypes for gene: KLC4 were set to spastic paraplegia
Penetrance for gene: KLC4 were set to Complete
Review for gene: KLC4 was set to RED
Added comment: Bayrakli (2015, 26423925). Affected, homozygous fs in three individuals in the same family.
One family, limited evidence
Diagnostic on Sheffield HSP panel
Sources: Literature
Hereditary spastic paraplegia v1.71 GCH1 Chris Buxton gene: GCH1 was added
gene: GCH1 was added to Hereditary spastic paraplegia. Sources: Literature
Mode of inheritance for gene: GCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GCH1 were set to 24509643; 21935284
Phenotypes for gene: GCH1 were set to Dystonia; Spastic paraplegia
Penetrance for gene: GCH1 were set to unknown
Review for gene: GCH1 was set to GREEN
Added comment: Fan (2014, 24509643) het for nonsense variant previously associated with dopa-responsive dystonia. Authors observe that Dopa-responsive Dystonia can resemble HSP

Lee (2011, 21935284), another example of DRD misdiagnosed as Cerebral palsy with GCH1 c.1A>T; p.Met1Leu missense
Diagnostic on Sheffield HSP panel
Sources: Literature
Early onset or syndromic epilepsy v0.1191 NDUFAF2 Ivone Leong Phenotypes for gene: NDUFAF2 were changed from to Mitochondrial complex I deficiency, 252010
Early onset or syndromic epilepsy v0.1190 NDUFA10 Ivone Leong Classified gene: NDUFA10 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1190 NDUFA10 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. Both OMIM and Gene2Phenotype have confirmed that NDUFA10 is associated with Leigh syndrome, and both have listed seizures as a phenotype.
There are 3 studies (PMID: 21150889; 26741492; 28247337) reporting 3 patients who have different variants in the NDUFA10 gene and have seizures.
Early onset or syndromic epilepsy v0.1190 NDUFA10 Ivone Leong Gene: ndufa10 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1189 NDUFA10 Ivone Leong Classified gene: NDUFA10 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1189 NDUFA10 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. Both OMIM and Gene2Phenotype confirm that NDUFA10 is associated with Leigh syndrome and both databases list seizures as a phenotype.
There are 3 studies (PMID: 21150889, 26741492, 28247337) describing 3 patients who have different variants in NDUFA10 who have seizures.
Early onset or syndromic epilepsy v0.1189 NDUFA10 Ivone Leong Gene: ndufa10 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1188 NDUFA10 Ivone Leong Marked gene: NDUFA10 as ready
Early onset or syndromic epilepsy v0.1188 NDUFA10 Ivone Leong Gene: ndufa10 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1188 NDUFA10 Ivone Leong Publications for gene: NDUFA10 were set to
Hereditary spastic paraplegia v1.71 FARS2 Chris Buxton edited their review of gene: FARS2: Changed publications: 30250868, 26553276, 29126765
Hereditary spastic paraplegia v1.71 FARS2 Chris Buxton gene: FARS2 was added
gene: FARS2 was added to Hereditary spastic paraplegia. Sources: Literature
Mode of inheritance for gene: FARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FARS2 were set to spastic paraplegia
Penetrance for gene: FARS2 were set to unknown
Review for gene: FARS2 was set to GREEN
Added comment: Sahai (2018, 30250868) FARS2 cpd hhet with pure spastic paraplegia syndrome associated with bilateral signal abnormalities in the dentate nuclei. Biochemical evalutatoin showed impacts on activity of impacted enzyme .

Yang (2016, 26553276), FARS cpd het on exome study, functional studies supportive. Phenotype is Spastic Paraplegia.

Vantroys (2017, 29126765) writes that FARS can be associated with (i) an epileptic phenotype, and (ii) a spastic paraplegia phenotype. Descroibes 2 probands with phenotype including spasticity with cpd het varaints in FARs
Sources: Literature
Early onset or syndromic epilepsy v0.1187 NDUFA10 Ivone Leong Mode of inheritance for gene: NDUFA10 was changed from to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v2.556 DDX59 Konstantinos Varvagiannis gene: DDX59 was added
gene: DDX59 was added to Intellectual disability. Sources: Literature,Expert Review
Mode of inheritance for gene: DDX59 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDX59 were set to 23972372; 28711741; 29127725
Phenotypes for gene: DDX59 were set to Orofaciodigital syndrome V, 174300
Penetrance for gene: DDX59 were set to Complete
Review for gene: DDX59 was set to GREEN
Added comment: Biallelic mutations in DDX59 cause Orofaciodigital syndrome V, 174300.

PMID: 23972372 reports on 6 individuals from 2 consanguineous Arab families. All 6 presented with palatal anomalies (cleft palate or bifid uvula), lobulated tongue, facial anomalies (frontal bossing and hypertelorism) as well as intellectual disability.

Individuals from the first family were homozygous for the Val367Gly (NM_001031725.4:c.1100T>G) variant while those from the second were homozygous for Gly534Arg (NM_001031725.4:c.1600G>A), both predicted to be pathogenic in silico. Immunoblot demonstrated reduced levels of the Val367Gly variant in patient fibroblasts (the other variant was probably not tested). Ddx59 was shown to be expressed in lips, palatal shelves and developing limb buds of mouse embryos.

PMID: 28711741 describes 3 further patients (from two consanguineous Pakistani families), presenting the cardinal features of orofaciodigital syndrome (though polydactyly was only reported in one of the three). Developmental delay was reported in all (in the first family one of the sibs had more severe delay with no speech at the age of 7 years, in the patient from the other family speech was limited to 2 words at school age). Affected individuals from both families were found to harbor a SNV leading to loss of a stop codon, thus extending the reading frame by 21 codons.

PMID: 29127725 reports on two sibs with a diagnosis of orofaciodigital syndrome born to non-consanguineous parents. ID was a feature in both. These individuals were homozygous for a frameshift variant. Reverse transcription PCR/semiquantitative PCR demonstrated reduction of the mutant transcript compared to the levels in wt controls (suggestive of incomplete NMD). Functional studies showed possible perturbation of the Sonic Hedgehog pathway. DDX59 expression in CNS from control post-mortem human brains was confirmed to be high (based on data generated in a previous study). Studies in Drosophila suggest reduced lifespan and neuronal defects secondary to mutations in mahe (the Drosophila homolog of DDX59).

As a result this gene can be considered for inclusion in the ID panel as green.
Sources: Literature, Expert Review
Hereditary spastic paraplegia v1.71 CYP27A1 Chris Buxton gene: CYP27A1 was added
gene: CYP27A1 was added to Hereditary spastic paraplegia. Sources: Literature
Mode of inheritance for gene: CYP27A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP27A1 were set to 25862734
Phenotypes for gene: CYP27A1 were set to progressive lower extremity spasticity,often disproportionate to any degree of weakness
Penetrance for gene: CYP27A1 were set to unknown
Review for gene: CYP27A1 was set to AMBER
Added comment: Nicholls (2015, 25862734)
Cerebrotendinous xanthomatosis AR disorder of bile acid metabolism can mimic more common conditions such as hereditary spastic paraparesis, or MS particularly if the phenotype is spinal xanthomatosis where the disease causes a spastic paraplegia
Associated with rased cholestanol. paper describes homozygous, previously reported CYP27A1 variant, c.1183C>T, p.Arg395Trp (R395W)
Diagnostic on Sheffield HSP panel
Sources: Literature
Early onset or syndromic epilepsy v0.1186 NDUFA10 Ivone Leong Phenotypes for gene: NDUFA10 were changed from to Leigh syndrome, 256000
Early onset or syndromic epilepsy v0.1185 NDUFA1 Ivone Leong Marked gene: NDUFA1 as ready
Early onset or syndromic epilepsy v0.1185 NDUFA1 Ivone Leong Gene: ndufa1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1185 NDUFA1 Ivone Leong Classified gene: NDUFA1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1185 NDUFA1 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. Both OMIM and Gene2Phenotype confirm that NDUFA1 is associated with Mitochondrial complex I deficiency and seizures is listed on both databases as a phenotype. There are three papers (PMID: 17262856,19185523, 29272804) reporting on 4 individuals with variants in the NDUFA1 gene and have seizures. There are currently 2 different NDUFA1 variants reported that are associated with Mitochondrial complex I deficiency.
Early onset or syndromic epilepsy v0.1185 NDUFA1 Ivone Leong Gene: ndufa1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1184 NDUFA1 Ivone Leong Publications for gene: NDUFA1 were set to
Hereditary spastic paraplegia v1.71 ARG1 Chris Buxton gene: ARG1 was added
gene: ARG1 was added to Hereditary spastic paraplegia. Sources: Literature
Mode of inheritance for gene: ARG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARG1 were set to 26310552; 23859858
Phenotypes for gene: ARG1 were set to Argininaemia; Progressive spastic tetraplegia
Penetrance for gene: ARG1 were set to unknown
Added comment: Spastic tetraplegia noted with ARG1 deficiency argininemia in neonates. Symptoms similar to cerebeal palsy so Dx is delayed
Wu (2015, 26310552) identified 9 ARG1 varaints in 7 patients.

Wu (2013, 23859858), similar paper to the above one. Progressive spastic tetraplegia, poor physical growth from 1 month to 4 years. When argininemia was found at the ages of 4 to 12 years, four of patients had mental retardation, and three had seizures. 6 ARG1 mutations identified.

On Sheffield HSP panel
Sources: Literature
Early onset or syndromic epilepsy v0.1183 NDUFA1 Ivone Leong Mode of inheritance for gene: NDUFA1 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early onset or syndromic epilepsy v0.1182 UFM1 Sarah Leigh Marked gene: UFM1 as ready
Early onset or syndromic epilepsy v0.1182 UFM1 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 3 variants reported in 3 unrelated cases in which seizures are a phenotypic feature.
Early onset or syndromic epilepsy v0.1182 UFM1 Sarah Leigh Gene: ufm1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1182 UFM1 Sarah Leigh Mode of inheritance for gene: UFM1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1181 UFM1 Sarah Leigh Classified gene: UFM1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1181 UFM1 Sarah Leigh Gene: ufm1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1180 UFC1 Sarah Leigh Marked gene: UFC1 as ready
Early onset or syndromic epilepsy v0.1180 UFC1 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 2 variants reported in unrelated cases in which seizures are a phenotypic feature.
Early onset or syndromic epilepsy v0.1180 UFC1 Sarah Leigh Gene: ufc1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1180 UFC1 Sarah Leigh Classified gene: UFC1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v0.1180 UFC1 Sarah Leigh Gene: ufc1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1179 UFC1 Sarah Leigh Publications for gene: UFC1 were set to 29868776
Early onset or syndromic epilepsy v0.1178 TELO2 Sarah Leigh Marked gene: TELO2 as ready
Early onset or syndromic epilepsy v0.1178 TELO2 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 7 variants reported in 7 unrelated cases, two of whome had seizures.
Early onset or syndromic epilepsy v0.1178 TELO2 Sarah Leigh Gene: telo2 has been classified as Amber List (Moderate Evidence).
Hereditary spastic paraplegia v1.71 REEP2 Chris Buxton edited their review of gene: REEP2: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary spastic paraplegia v1.71 REEP2 Chris Buxton reviewed gene: REEP2: Rating: AMBER; Mode of pathogenicity: None; Publications: 28491902; Phenotypes: spastic paprplegia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1178 TELO2 Sarah Leigh Classified gene: TELO2 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v0.1178 TELO2 Sarah Leigh Gene: telo2 has been classified as Amber List (Moderate Evidence).
Hereditary spastic paraplegia v1.71 MAG Chris Buxton edited their review of gene: MAG: Changed publications: 24482476
Hereditary spastic paraplegia v1.71 MAG Chris Buxton gene: MAG was added
gene: MAG was added to Hereditary spastic paraplegia. Sources: Literature
Mode of inheritance for gene: MAG was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MAG were set to spastic paprplegia
Penetrance for gene: MAG were set to unknown
Review for gene: MAG was set to RED
Added comment: 1 family Novarino (2014, 24482476). Homozygous Cys430Gly with HSp phenotype. No other detail. 1 family. Limited evidence
Diagnostic on Sheffield HSP panel
Sources: Literature
Early onset or syndromic epilepsy v0.1177 TELO2 Sarah Leigh Publications for gene: TELO2 were set to
Early onset or syndromic epilepsy v0.1176 TELO2 Sarah Leigh Phenotypes for gene: TELO2 were changed from to You-Hoover-Fong syndrome 616954
Hereditary spastic paraplegia v1.71 KDM5C Chris Buxton gene: KDM5C was added
gene: KDM5C was added to Hereditary spastic paraplegia. Sources: Literature
Mode of inheritance for gene: KDM5C 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: KDM5C were set to 10982473; 15586325; 26919706
Phenotypes for gene: KDM5C were set to Intellectual disability; developmental delay; progressive spasticity; epilepsy; hypothyroidism
Penetrance for gene: KDM5C were set to unknown
Review for gene: KDM5C was set to RED
Added comment: Claes (2000, 10982473) reported candidate HSP locus Xp21.1-Xq21.3. Jensen (2005, 15586325) identified as JARID1C(syn)/KDM5C gene: c.2191C>T Leu731Phe. 4 males in same pedigree: two generations present with severe MR, slowly progressive spastic paraplegia, facial hypotonia, and maxillary hypoplasia. Additional features are aggressive behavior and strabismus;

Fujita (2016, 26919706). Two different fs deletion variants. maternal reversion mechanims? Progressive spasticity component to phenotype.

Currently diagnostic on Sheffield's HSP panel
Sources: Literature
Early onset or syndromic epilepsy v0.1175 PHACTR1 Sarah Leigh Marked gene: PHACTR1 as ready
Early onset or syndromic epilepsy v0.1175 PHACTR1 Sarah Leigh Added comment: Comment when marking as ready: Not associated with phenotype in OMIM or in Gen2Phen. At least 3 variants reported in unrelated cases, together with supportive functional studies (PMIDs: 23033978, 28135719), which support a dominant negative mode of action or incomplete penetrance.
Early onset or syndromic epilepsy v0.1175 PHACTR1 Sarah Leigh Gene: phactr1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1175 PHACTR1 Sarah Leigh Added comment: Comment on mode of pathogenicity: Proposed dominant negative or incomplete penetrance mode of action (PMIDs: 23033978, 28135719)
Early onset or syndromic epilepsy v0.1175 PHACTR1 Sarah Leigh Mode of pathogenicity for gene: PHACTR1 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Early onset or syndromic epilepsy v0.1174 PHACTR1 Sarah Leigh Classified gene: PHACTR1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1174 PHACTR1 Sarah Leigh Gene: phactr1 has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.71 IBA57 Chris Buxton gene: IBA57 was added
gene: IBA57 was added to Hereditary spastic paraplegia. Sources: Literature
Mode of inheritance for gene: IBA57 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IBA57 were set to 25609768
Phenotypes for gene: IBA57 were set to spastic paraplegia
Penetrance for gene: IBA57 were set to unknown
Review for gene: IBA57 was set to RED
Added comment: Lossos (2015, 25609768). Homozygous donor splice-site mutation in the IBA57. mRNA studies done, some protein studies support pathogenicity. 1 family, limited evidence.
Sources: Literature
Early onset or syndromic epilepsy v0.1173 MACF1 Sarah Leigh Marked gene: MACF1 as ready
Early onset or syndromic epilepsy v0.1173 MACF1 Sarah Leigh Added comment: Comment when marking as ready: Not associated with phenotype in OMIM (last updated for this gene 05/17/2011) or in Gen2Phen. At least 7 variants reported in unrelated cases with intellectual disability, seizures, lissencephalyand brainstem dysplasia.
Early onset or syndromic epilepsy v0.1173 MACF1 Sarah Leigh Gene: macf1 has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.71 ABCD1 Chris Buxton edited their review of gene: ABCD1: Changed publications: 11810273, 27084228, 11739809, 26049658
Hereditary spastic paraplegia v1.71 ABCD1 Chris Buxton gene: ABCD1 was added
gene: ABCD1 was added to Hereditary spastic paraplegia. Sources: Literature
Mode of inheritance for gene: ABCD1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: ABCD1 were set to Hereditary spastic paraplegia; adrenal failure; VLCFA accumulation
Penetrance for gene: ABCD1 were set to unknown
Review for gene: ABCD1 was set to GREEN
Added comment: Guimarães (2001, 11810273), X-linked adrenoleukodystrophy.
Spastic paraparesis with neurophysiologic abnormalities with an altered spinal cord MRI and a normal cerebral MRI. 2 different splice variants described

Balicza (2016, 27084228), hereditary spastic paraplegia phenotype
Spastic paraparesis; c.1553G>C p.R518P (no details)

O'Neill (2001, 11739809), X-linked dominant hereditary spastic paraparesis
Obligate female carriers affected, deletion 26 bp nt. 369-394, 5'UTR-cd.3

Koutsis (2015, 26049658) progressive spastic paraplegia with raised VLCFA, ABCD1 (c.1174_1178del, p.Leu392Serfs*7)

Gene is on Sheffield's HSP panel
Sources: Literature
Hereditary spastic paraplegia v1.71 ZEB2 Chris Buxton reviewed gene: ZEB2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mowat Wilson; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary spastic paraplegia v1.71 WDR48 Chris Buxton reviewed gene: WDR48: Rating: RED; Mode of pathogenicity: None; Publications: 22717650; Phenotypes: Early onset spastic paraparesis, mild intellectual disability, kyphosis, pectus carinatum, hypertrichosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary spastic paraplegia v1.71 TFG Chris Buxton reviewed gene: TFG: Rating: GREEN; Mode of pathogenicity: None; Publications: 23479643, 27492651, 27601211; Phenotypes: spastic paraplegia, optic atrophy, neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary spastic paraplegia v1.71 TECPR2 Chris Buxton edited their review of gene: TECPR2: Changed phenotypes: complex HSP/dysautonomia
Hereditary spastic paraplegia v1.71 TECPR2 Chris Buxton reviewed gene: TECPR2: Rating: AMBER; Mode of pathogenicity: None; Publications: 23176824, 25590979; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1173 MACF1 Sarah Leigh Added comment: Comment on mode of inheritance: Authors of PMID 30471716 suggest that a gain of function or dominant negative mode of action as truncating variant are reported in EXAC
Early onset or syndromic epilepsy v0.1173 MACF1 Sarah Leigh Mode of inheritance for gene: MACF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v0.1172 MACF1 Sarah Leigh Publications for gene: MACF1 were set to doi.org/10.1016/j.ajhg.2018.10.019
Early onset or syndromic epilepsy v0.1171 MACF1 Sarah Leigh Classified gene: MACF1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1171 MACF1 Sarah Leigh Gene: macf1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1170 MACF1 Sarah Leigh Mode of inheritance for gene: MACF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary spastic paraplegia v1.71 PGAP1 Chris Buxton reviewed gene: PGAP1: Rating: RED; Mode of pathogenicity: None; Publications: 24482476; Phenotypes: not stated; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary spastic paraplegia v1.71 MTPAP Chris Buxton reviewed gene: MTPAP: Rating: AMBER; Mode of pathogenicity: None; Publications: 20970105, 25008111, 27391121; Phenotypes: cerebellar ataxia, spastic paraparesis, dysarthria, optic atrophy, learning difficulties; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary spastic paraplegia v1.71 MTPAP Chris Buxton Deleted their review
Hereditary spastic paraplegia v1.71 MTPAP Chris Buxton commented on gene: MTPAP
Ductal plate malformation v0.72 KCNN3 Ivone Leong Marked gene: KCNN3 as ready
Ductal plate malformation v0.72 KCNN3 Ivone Leong Gene: kcnn3 has been classified as Red List (Low Evidence).
Hereditary spastic paraplegia v1.71 MARS2 Chris Buxton reviewed gene: MARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22448145; Phenotypes: Spastic Ataxia, Leukoencephalopathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ductal plate malformation v0.72 KCNN3 Ivone Leong Classified gene: KCNN3 as Red List (low evidence)
Ductal plate malformation v0.72 KCNN3 Ivone Leong Added comment: Comment on list classification: Demoted from green to red. KCNN3 does not have an OMIM ID and has no associated phenotypes on Gene2Phenotype. There is only one paper (PMID: 26658685) describing one family with four affected individuals presenting with idiopathic non-cirrhotic portal hypertension who have a missense variant in KCNN3. There are no other reports or reported variants in this gene.
Ductal plate malformation v0.72 KCNN3 Ivone Leong Gene: kcnn3 has been classified as Red List (Low Evidence).
DDG2P v0.16 KLHL7 Rebecca Foulger Phenotypes for gene: KLHL7 were changed from Cold-induced sweating syndrome type 1 (CISS1-like Phenotype Associated with Early-Onset Retinitis Pigmentosa to Cold-induced sweating syndrome type 1 (CISS1-like Phenotype Associated with Early-Onset Retinitis Pigmentosa; Crisponi/CISS1-like phenotype associated with early-onset retinitis pigmentosa
DDG2P v0.15 SLC25A4 Rebecca Foulger Phenotypes for gene: SLC25A4 were changed from Severe Early-Onset Mitochondrial Disease and Loss of Mitochondrial DNA Copy Number to Severe Early-Onset Mitochondrial Disease and Loss of Mitochondrial DNA Copy Number; Fontaine progeroid syndrome
Ductal plate malformation v0.71 KCNN3 Ivone Leong All sources for gene: KCNN3 were removed
DDG2P v0.14 DNMT3A Rebecca Foulger commented on gene: DNMT3A: Added watchlist tag to highlight different DD-G2P ratings for different gene:disorder associations.
DDG2P v0.14 DNMT3A Rebecca Foulger Classified gene: DNMT3A as Amber List (moderate evidence)
DDG2P v0.14 DNMT3A Rebecca Foulger Added comment: Comment on list classification: Updated rating from Green to Amber while panel is V0 and unreviewed, based on DDG2P rating for newly added disorder: Rated confirmed by DDG2P for Tatton-Brown Rahman syndrome (OVERGROWTH SYNDROME WITH INTELLECTUAL DISABILITY), formerly called OVERGROWTH SYNDROME WITH INTELLECTUAL DISABILITY 615879. Rated probable by DDG2P for Microcephalic primordial dwarfism.
DDG2P v0.14 DNMT3A Rebecca Foulger Gene: dnmt3a has been classified as Amber List (Moderate Evidence).
DDG2P v0.13 DNMT3A Rebecca Foulger Tag watchlist tag was added to gene: DNMT3A.
Ductal plate malformation v0.70 KCNN3 Ivone Leong Added comment: Comment on mode of inheritance: The publication (PMID: 26658685) describes it as an autosomal dominant variant.
Ductal plate malformation v0.70 KCNN3 Ivone Leong Mode of inheritance for gene: KCNN3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DDG2P v0.13 DNMT3A Rebecca Foulger Phenotypes for gene: DNMT3A were changed from OVERGROWTH SYNDROME WITH INTELLECTUAL DISABILITY 615879 to Tatton-Brown Rahman syndrome (OVERGROWTH SYNDROME WITH INTELLECTUAL DISABILITY) 615879; Microcephalic primordial dwarfism
Ductal plate malformation v0.69 KCNN3 Ivone Leong Phenotypes for gene: KCNN3 were changed from portal hypertension; varices; splenomegaly to No OMIM number; portal hypertension; varices; splenomegaly
Ductal plate malformation v0.68 KCNN3 Ivone Leong Publications for gene: KCNN3 were set to 26658685
Ductal plate malformation v0.67 KCNN3 Ivone Leong Publications for gene: KCNN3 were set to PMID: 26658685
DDG2P v0.12 COG4 Rebecca Foulger commented on gene: COG4: Added watchlist tag to highlight different DD-G2P ratings for different gene:disorder associations.
DDG2P v0.12 COG4 Rebecca Foulger Tag watchlist tag was added to gene: COG4.
Early onset or syndromic epilepsy v0.1169 MACF1 Sarah Leigh Publications for gene: MACF1 were set to
DDG2P v0.12 COG4 Rebecca Foulger Classified gene: COG4 as Amber List (moderate evidence)
DDG2P v0.12 COG4 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Green to Amber while panel is still V0 and unreviewed: Rated confirmed by DDG2P for COG4-CDG 319493, and Rated probable for recently-added Saul-Wilson syndrome.
DDG2P v0.12 COG4 Rebecca Foulger Gene: cog4 has been classified as Amber List (Moderate Evidence).
Hereditary spastic paraplegia v1.71 GJC2 Chris Buxton reviewed gene: GJC2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
DDG2P v0.11 COG4 Rebecca Foulger Added comment: Comment on mode of inheritance: Updated MOI from 'biallelic to both monoallelic and biallelic': Multiple MOIs in DD-G2P download: monoallelic for Saul-Wilson syndrome, and biallelic for COG4-CDG.
DDG2P v0.11 COG4 Rebecca Foulger Mode of inheritance for gene: COG4 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1168 GNB5 Sarah Leigh Marked gene: GNB5 as ready
Early onset or syndromic epilepsy v0.1168 GNB5 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. Sufficient variants and unrelated cases for this gene to be rated green.
Early onset or syndromic epilepsy v0.1168 GNB5 Sarah Leigh Gene: gnb5 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1168 GNB5 Sarah Leigh Classified gene: GNB5 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1168 GNB5 Sarah Leigh Added comment: Comment on list classification: Based on cited literature and review by Konstantinos Varvagiannis.
Early onset or syndromic epilepsy v0.1168 GNB5 Sarah Leigh Gene: gnb5 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1167 GNB5 Sarah Leigh Classified gene: GNB5 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1167 GNB5 Sarah Leigh Gene: gnb5 has been classified as Green List (High Evidence).
DDG2P v0.10 COG4 Rebecca Foulger Phenotypes for gene: COG4 were changed from COG4-CDG 319493 to COG4-CDG 319493; Saul-Wilson syndrome
DDG2P v0.9 SLC25A4 Rebecca Foulger edited their review of gene: SLC25A4: Added comment: New gene:disorder association added to DDG2P on 08/11/2018: Fontaine progeroid syndrome. Rated probable in DDG2P for both Severe Early-Onset Mitochondrial Disease and Loss of Mitochondrial DNA Copy Number, and Fontaine progeroid syndrome. DG2P mode of pathogenicity for both Severe Early-Onset Mitochondrial Disease and Loss of Mitochondrial DNA Copy Number, and Fontaine progeroid syndrome: all missense/in frame.; Changed publications: 30329211; Changed phenotypes: Fontaine progeroid syndrome; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
DDG2P v0.9 LZTR1 Rebecca Foulger reviewed gene: LZTR1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
DDG2P v0.9 RAC3 Rebecca Foulger reviewed gene: RAC3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
DDG2P v0.9 NFIB Rebecca Foulger reviewed gene: NFIB: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
DDG2P v0.9 KCNK4 Rebecca Foulger reviewed gene: KCNK4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
DDG2P v0.9 KLHL7 Rebecca Foulger edited their review of gene: KLHL7: Added comment: New gene:disorder association added to DDG2P on 08/11/2018: Crisponi/CISS1-like phenotype associated with early-onset retinitis pigmentosa. Rated probable in DDG2P for both Cold-induced sweating syndrome type 1 (CISS1-like Phenotype Associated with Early-Onset Retinitis Pigmentosa, and Crisponi/CISS1-like phenotype associated with early-onset retinitis pigmentosa. No MOI listed in DD-G2P for Crisponi/CISS1-like phenotype associated with early-onset retinitis pigmentosa. No MOP listed in DD-G2P for Crisponi/CISS1-like phenotype associated with early-onset retinitis pigmentosa.; Changed phenotypes: Crisponi/CISS1-like phenotype associated with early-onset retinitis pigmentosa
DDG2P v0.9 COG4 Rebecca Foulger edited their review of gene: COG4: Added comment: New gene:disorder association added to DDG2P on 07/11/2018: Saul-Wilson syndrome. Multiple DDG2P ratings: Rated confirmed for COG4-CDG 319493 and Rated probable for Saul-Wilson syndrome: Multiple MOPs in DDG2P: gain of function for Saul-Wilson syndrome, and loss of function for COG4-CDG 319493. Multiple MOIs in DD-G2P download: monoallelic for Saul-Wilson syndrome, and biallelic for COG4-CDG.; Changed phenotypes: Saul-Wilson syndrome; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
DDG2P v0.9 SLC10A7 Rebecca Foulger reviewed gene: SLC10A7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
DDG2P v0.9 DNMT3A Rebecca Foulger edited their review of gene: DNMT3A: Added comment: New gene:disorder association added to DDG2P on 06/11/2018: Microcephalic primordial dwarfism. Multiple DDG2P ratings: Rated confirmed for OVERGROWTH SYNDROME WITH INTELLECTUAL DISABILITY 615879 and rated probable for Microcephalic primordial dwarfism. Multiple MOPs in DDG2P: gain of function for Microcephalic primordial dwarfism, and loss of function for OVERGROWTH SYNDROME WITH INTELLECTUAL DISABILITY 615879.; Changed phenotypes: Microcephalic primordial dwarfism; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary spastic paraplegia v1.71 GAD1 Chris Buxton reviewed gene: GAD1: Rating: RED; Mode of pathogenicity: None; Publications: 15571623; Phenotypes: Cerebral palsy, spastic, symmetric; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary spastic paraplegia v1.71 ENTPD1 Chris Buxton reviewed gene: ENTPD1: Rating: RED; Mode of pathogenicity: None; Publications: 29691679, 24482476; Phenotypes: cognitive delay, spastic paraplegia, dystonia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary spastic paraplegia v1.71 ARSI Chris Buxton reviewed gene: ARSI: Rating: RED; Mode of pathogenicity: None; Publications: 24482476; Phenotypes: Abnormal gait, Nonambulatory, Absent deep tendon reflexes, Pes equinovarus, Corpus callosum & cerebellar hypoplasia, colpocephaly, Severe sensory/motor polyneuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ductal plate malformation v0.66 PEX1 Ivone Leong Marked gene: PEX1 as ready
Ductal plate malformation v0.66 PEX1 Ivone Leong Gene: pex1 has been classified as Red List (Low Evidence).
Ductal plate malformation v0.66 PEX1 Ivone Leong Classified gene: PEX1 as Red List (low evidence)
Ductal plate malformation v0.66 PEX1 Ivone Leong Added comment: Comment on list classification: Demoted from amber to red. Based on the comment by Anna de Burca (Genomics England Curator).
Ductal plate malformation v0.66 PEX1 Ivone Leong Gene: pex1 has been classified as Red List (Low Evidence).
Ductal plate malformation v0.65 NOTCH2 Ivone Leong Marked gene: NOTCH2 as ready
Ductal plate malformation v0.65 NOTCH2 Ivone Leong Gene: notch2 has been classified as Red List (Low Evidence).
Ductal plate malformation v0.65 NOTCH2 Ivone Leong Classified gene: NOTCH2 as Red List (low evidence)
Ductal plate malformation v0.65 NOTCH2 Ivone Leong Added comment: Comment on list classification: Demoted from amber to red. Based on the comment by Anna de Burca (Genomics England Curator).
Ductal plate malformation v0.65 NOTCH2 Ivone Leong Gene: notch2 has been classified as Red List (Low Evidence).
Ductal plate malformation v0.64 JAG1 Ivone Leong Marked gene: JAG1 as ready
Ductal plate malformation v0.64 JAG1 Ivone Leong Gene: jag1 has been classified as Red List (Low Evidence).
Ductal plate malformation v0.64 JAG1 Ivone Leong Classified gene: JAG1 as Red List (low evidence)
Ductal plate malformation v0.64 JAG1 Ivone Leong Added comment: Comment on list classification: Demoted from amber to red. Based on the comment by Anna de Burca (Genomics England Curator).
Ductal plate malformation v0.64 JAG1 Ivone Leong Gene: jag1 has been classified as Red List (Low Evidence).
Hereditary spastic paraplegia v1.71 AMPD2 Chris Buxton reviewed gene: AMPD2: Rating: RED; Mode of pathogenicity: None; Publications: 24482476; Phenotypes: spastic paprplegia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
DDG2P v0.8 LZTR1 Rebecca Foulger gene: LZTR1 was added
gene: LZTR1 was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: LZTR1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: LZTR1 were set to 30368668; 29959388
Phenotypes for gene: LZTR1 were set to Noonan syndrome
Mode of pathogenicity for gene: LZTR1 was set to Other - please provide details in the comments
DDG2P v0.8 RAC3 Rebecca Foulger gene: RAC3 was added
gene: RAC3 was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: RAC3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RAC3 were set to 30293988
Phenotypes for gene: RAC3 were set to Neurodevelopment disorder
Mode of pathogenicity for gene: RAC3 was set to Other - please provide details in the comments
DDG2P v0.8 NFIB Rebecca Foulger gene: NFIB was added
gene: NFIB was added to DDG2P. Sources: DD-Gene2Phenotype,Expert Review Amber
Mode of inheritance for gene: NFIB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: NFIB were set to 30388402
Phenotypes for gene: NFIB were set to Intellectual disability with macrocephaly
DDG2P v0.8 KCNK4 Rebecca Foulger gene: KCNK4 was added
gene: KCNK4 was added to DDG2P. Sources: Expert Review Red,DD-Gene2Phenotype
Mode of inheritance for gene: KCNK4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KCNK4 were set to 30290154
Phenotypes for gene: KCNK4 were set to FHEIG (facial dysmorphism, hypertrichosis, epilepsy, intellectual disability/developmental delay, and gingival overgrowth)
Mode of pathogenicity for gene: KCNK4 was set to Other - please provide details in the comments
DDG2P v0.8 SLC10A7 Rebecca Foulger gene: SLC10A7 was added
gene: SLC10A7 was added to DDG2P. Sources: Expert Review Green,DD-Gene2Phenotype
Mode of inheritance for gene: SLC10A7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC10A7 were set to 29878199; 30082715
Phenotypes for gene: SLC10A7 were set to Chondrodysplasia with multiple dislocations and amelogenesis imperfecta
Ductal plate malformation v0.63 NOTCH2 Anna de Burca reviewed gene: NOTCH2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ductal plate malformation v0.63 JAG1 Anna de Burca reviewed gene: JAG1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ductal plate malformation v0.63 PEX1 Anna de Burca reviewed gene: PEX1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1166 RMND1 Sarah Leigh Marked gene: RMND1 as ready
Early onset or syndromic epilepsy v0.1166 RMND1 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 4 variants reported in 3 unrelated cases in which seizures are a phenotypic feature.
Early onset or syndromic epilepsy v0.1166 RMND1 Sarah Leigh Gene: rmnd1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1166 RMND1 Sarah Leigh Classified gene: RMND1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1166 RMND1 Sarah Leigh Gene: rmnd1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1165 RMND1 Sarah Leigh Publications for gene: RMND1 were set to
Early onset or syndromic epilepsy v0.1164 NDUFA1 Ivone Leong Phenotypes for gene: NDUFA1 were changed from to Mitochondrial complex I deficiency, 252010
Hereditary spastic paraplegia v1.71 NT5C2 Chris Buxton reviewed gene: NT5C2: Rating: AMBER; Mode of pathogenicity: None; Publications: 28884889, 28327087, 29123918; Phenotypes: spastic paraplegia, mental retardation, Thin Corpus Callosum associated HSP; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1163 NDE1 Ivone Leong Marked gene: NDE1 as ready
Early onset or syndromic epilepsy v0.1163 NDE1 Ivone Leong Gene: nde1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1163 NDE1 Ivone Leong Classified gene: NDE1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1163 NDE1 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. NDE1 is confirmed to be a causative gene of Lissencephaly by OMIM and Gene2Phenotype. Both sources list seizures as a phenotype of the disease. There are 3 papers (PMID:21529752, 21529751, 22526350) reporting on 5 unrelated families with 8 affected individuals who have Lissencephaly and have different variants in the NDE1 gene. All patients are of Pakistani, Turkish or Saudi Arabian descent.
Early onset or syndromic epilepsy v0.1163 NDE1 Ivone Leong Gene: nde1 has been classified as Green List (High Evidence).
Intellectual disability v2.556 DPH1 Konstantinos Varvagiannis gene: DPH1 was added
gene: DPH1 was added to Intellectual disability. Sources: Literature,Expert Review
Mode of inheritance for gene: DPH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DPH1 were set to 25558065; 26220823; 29362492; 29410513
Phenotypes for gene: DPH1 were set to Developmental delay with short stature, dysmorphic features, and sparse hair, 616901
Penetrance for gene: DPH1 were set to Complete
Review for gene: DPH1 was set to GREEN
gene: DPH1 was marked as current diagnostic
Added comment: Biallelic mutations in DPH1 cause Developmental delay with short stature, dysmorphic features, and sparse hair, MIM 616901.

Overall 11 patients from 6 different families have probably been reported in detail. DD/ID is a universal feature.

In PMID 25558065, Alazami et al. identified 1 patient from the same consanguineous Saudi Arabian family (of 8 total similarly affected individuals) homozygous for the Leu234Pro (NM_001383.3:c.701T>C) variant. This individual was part of a large cohort of patients with neurogenetic disorders from consanguineous families. The phenotype is not described in detail.

In PMID 26220823 Louks et al. report on 4 patients from 3 families belonging to the same genetic isolate from North America and provide details on 4 of the individuals identified by Alazami et al.

The individuals identified in this study were homozygous for Met6Lys which was however predicted to be benign and tolerated (by PolyPhen2 and SIFT respectively) in silico.

DD/ID, unusual skull shape, ectodermal anomalies were universal (8/8) with additional features including short stature (7/8), renal (4/6) or cardiac anomalies (3/8). Some facial features appeared to be common, too.

Functional studies were not performed. However Dph1 pathogenic variants in mice result in restricted growth, craniofacial and developmental defects similar to the human phenotypes (PMIDs 14744934 and 24895408 are cited).

PMIDs 29362492 and 29410513 report on 3 further patients with similar (as well as some additional) features including DD/ID. The individual in the first article was compound heterozygous for a missense (Leu164Pro) and a frameshift variant (c.289delG) while 2 sibs born to consanguineous parents in the second article were homozygous for a frameshift variant (c.1227delG).

The phenotype appears to be consistent among all the published patients.

DPH1 is included in gene panels for intellectual disability offered by different diagnostic laboratories.

As a result, this gene can be considered for inclusion in this panel as green.
Sources: Literature, Expert Review
Early onset or syndromic epilepsy v0.1162 NDE1 Ivone Leong Publications for gene: NDE1 were set to
DDG2P v0.7 DYNC2H1 Rebecca Foulger Classified gene: DYNC2H1 as Green List (high evidence)
DDG2P v0.7 DYNC2H1 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Grey to Green: Rating should have been Green in original file upload because DDG2P rating is confirmed for both disorders: ASPHYXIATING THORACIC DYSTROPHY TYPE 3, and SHORT RIB-POLYDACTYLY SYNDROME TYPE 3.
DDG2P v0.7 DYNC2H1 Rebecca Foulger Gene: dync2h1 has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.71 KIF1C Chris Buxton reviewed gene: KIF1C: Rating: AMBER; Mode of pathogenicity: None; Publications: 24482476, 24319291, 24482476, 17273843; Phenotypes: cerebellar ataxia, dysarthria, variable spasticity of the lower limbs, Cognition is not affected; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
DDG2P v0.6 NPHP3 Rebecca Foulger Classified gene: NPHP3 as Green List (high evidence)
DDG2P v0.6 NPHP3 Rebecca Foulger Added comment: Comment on list classification: Updated rating to Green: Rating should have been Green in original fileupload since Original DDG2P rating is confirmed for all 3 DDG2P disorders; MECKEL SYNDROME TYPE 7 267010, RENAL-HEPATIC-PANCREATIC DYSPLASIA 208540 and NEPHRONOPHTHISIS TYPE 3 604387.
DDG2P v0.6 NPHP3 Rebecca Foulger Gene: nphp3 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1161 RMND1 Sarah Leigh Phenotypes for gene: RMND1 were changed from to Combined oxidative phosphorylation deficiency 11, 614922
Early onset or syndromic epilepsy v0.1160 RMND1 Sarah Leigh Mode of inheritance for gene: RMND1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1159 RFT1 Sarah Leigh Marked gene: RFT1 as ready
Early onset or syndromic epilepsy v0.1159 RFT1 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 7 variants reported in at least 6 unrelated cases in which seizures are a phenotypic feature.
Early onset or syndromic epilepsy v0.1159 RFT1 Sarah Leigh Gene: rft1 has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.71 ARL6IP1 Chris Buxton reviewed gene: ARL6IP1: Rating: AMBER; Mode of pathogenicity: None; Publications: 28471035, 24482476; Phenotypes: spastic paraplegia, sensory and motor polyneuropathy, congenital insensitivity to pain, acromutilation, spastic paraplegia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1159 RFT1 Sarah Leigh Classified gene: RFT1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1159 RFT1 Sarah Leigh Gene: rft1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1158 RFT1 Sarah Leigh Mode of inheritance for gene: RFT1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1157 RFT1 Sarah Leigh Publications for gene: RFT1 were set to
Early onset or syndromic epilepsy v0.1156 NDE1 Ivone Leong Mode of inheritance for gene: NDE1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary spastic paraplegia v1.71 AP5Z1 Chris Buxton reviewed gene: AP5Z1: Rating: AMBER; Mode of pathogenicity: None; Publications: 27606357; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1155 RFT1 Sarah Leigh Phenotypes for gene: RFT1 were changed from to Congenital disorder of glycosylation, type In, 612015
Early onset or syndromic epilepsy v0.1154 NDE1 Ivone Leong Phenotypes for gene: NDE1 were changed from to Lissencephaly 4 (with microcephaly), 614019
Early onset or syndromic epilepsy v0.1153 MED12 Ivone Leong Marked gene: MED12 as ready
Early onset or syndromic epilepsy v0.1153 MED12 Ivone Leong Gene: med12 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1153 MED12 Ivone Leong Classified gene: MED12 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1153 MED12 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green, based on the information provided previously.
Early onset or syndromic epilepsy v0.1153 MED12 Ivone Leong Gene: med12 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1152 RARS2 Sarah Leigh Mode of inheritance for gene: RARS2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1151 RARS2 Sarah Leigh Classified gene: RARS2 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1151 RARS2 Sarah Leigh Gene: rars2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1150 RARS2 Sarah Leigh Marked gene: RARS2 as ready
Early onset or syndromic epilepsy v0.1150 RARS2 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 5 variants reported in 4 unrelated cases, in which seizures are a phenotypic feature.
Early onset or syndromic epilepsy v0.1150 RARS2 Sarah Leigh Gene: rars2 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1150 RARS2 Sarah Leigh Phenotypes for gene: RARS2 were changed from to Pontocerebellar hypoplasia, type 6, 611523
Early onset or syndromic epilepsy v0.1149 RARS2 Sarah Leigh Publications for gene: RARS2 were set to
Early onset or syndromic epilepsy v0.1148 KRAS Ivone Leong Marked gene: KRAS as ready
Early onset or syndromic epilepsy v0.1148 KRAS Ivone Leong Gene: kras has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1148 KRAS Ivone Leong Classified gene: KRAS as Green List (high evidence)
Early onset or syndromic epilepsy v0.1148 KRAS Ivone Leong Added comment: Comment on list classification: Promoted from amber to green as an additional report on a patient with a variant in the KRAS gene who also has seizures (PMID: 17601930).
Early onset or syndromic epilepsy v0.1148 KRAS Ivone Leong Gene: kras has been classified as Green List (High Evidence).
Intellectual disability v2.556 RARS2 Sarah Leigh Publications for gene: RARS2 were set to
Early onset or syndromic epilepsy v0.1147 KRAS Ivone Leong Publications for gene: KRAS were set to 21871821; 23059812; 16474405; 21871821
Early onset or syndromic epilepsy v0.1146 RAB18 Sarah Leigh Marked gene: RAB18 as ready
Early onset or syndromic epilepsy v0.1146 RAB18 Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 4 variants reported 3 unrelated cases, each of the variants was associated with at least one case in which seizures are a phenotypic feature.
Early onset or syndromic epilepsy v0.1146 RAB18 Sarah Leigh Gene: rab18 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1146 HCN2 Ivone Leong Marked gene: HCN2 as ready
Early onset or syndromic epilepsy v0.1146 HCN2 Ivone Leong Gene: hcn2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1146 RAB18 Sarah Leigh Publications for gene: RAB18 were set to 15216543
Ductal plate malformation v0.63 TERT Ivone Leong Marked gene: TERT as ready
Ductal plate malformation v0.63 TERT Ivone Leong Added comment: Comment when marking as ready: There is not enough evidence to suggest TERT causes ductal plate malformation.
Ductal plate malformation v0.63 TERT Ivone Leong Gene: tert has been classified as Amber List (Moderate Evidence).
Ductal plate malformation v0.63 TERT Ivone Leong Publications for gene: TERT were set to
Ductal plate malformation v0.62 TERC Ivone Leong Marked gene: TERC as ready
Ductal plate malformation v0.62 TERC Ivone Leong Added comment: Comment when marking as ready: There is not enough evidence to support promoting TERC to a green gene on this panel.
Ductal plate malformation v0.62 TERC Ivone Leong Gene: terc has been classified as Amber List (Moderate Evidence).
Ductal plate malformation v0.62 TERC Ivone Leong Publications for gene: TERC were set to
Ductal plate malformation v0.61 STN1 Ivone Leong Marked gene: STN1 as ready
Ductal plate malformation v0.61 STN1 Ivone Leong Added comment: Comment when marking as ready: There is not enough evidence to support the promotion of STN1 to a green gene on this panel.
Ductal plate malformation v0.61 STN1 Ivone Leong Gene: stn1 has been classified as Amber List (Moderate Evidence).
Ductal plate malformation v0.61 STN1 Ivone Leong Publications for gene: STN1 were set to
Ductal plate malformation v0.60 PEX1 Ivone Leong Publications for gene: PEX1 were set to
Ductal plate malformation v0.59 RTEL1 Ivone Leong Marked gene: RTEL1 as ready
Ductal plate malformation v0.59 RTEL1 Ivone Leong Added comment: Comment when marking as ready: There is not enough evidence to promote RTEL1 to a green gene for the ductal plate malformation panel. Therefore, keeping it as amber.
Ductal plate malformation v0.59 RTEL1 Ivone Leong Gene: rtel1 has been classified as Amber List (Moderate Evidence).
Ductal plate malformation v0.59 RTEL1 Ivone Leong Publications for gene: RTEL1 were set to
Ductal plate malformation v0.58 SEC61B Ivone Leong Marked gene: SEC61B as ready
Ductal plate malformation v0.58 SEC61B Ivone Leong Added comment: Comment when marking as ready: There is currently not enough evidence to promote SEC61B to a green gene; therefore, have applied the 'Watchlist' tag.
Ductal plate malformation v0.58 SEC61B Ivone Leong Gene: sec61b has been classified as Amber List (Moderate Evidence).
Ductal plate malformation v0.58 SEC61B Ivone Leong Mode of inheritance for gene: SEC61B was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ductal plate malformation v0.57 SEC61B Ivone Leong Publications for gene: SEC61B were set to
Ductal plate malformation v0.56 RPGRIP1L Ivone Leong Marked gene: RPGRIP1L as ready
Ductal plate malformation v0.56 RPGRIP1L Ivone Leong Added comment: Comment when marking as ready: RPGRIP1L is a causative gene of Meckel syndrome and different variants have been reported in this gene associated with this syndrome in 3+ unrelated patients (PMID:17558409, 19574260).
Ductal plate malformation v0.56 RPGRIP1L Ivone Leong Gene: rpgrip1l has been classified as Green List (High Evidence).
Ductal plate malformation v0.56 CC2D2A Ivone Leong Marked gene: CC2D2A as ready
Ductal plate malformation v0.56 CC2D2A Ivone Leong Added comment: Comment when marking as ready: CC2D2A causes congenital hepatic fibrosis, which is a phenotype of Ductal plate malformation
Ductal plate malformation v0.56 CC2D2A Ivone Leong Gene: cc2d2a has been classified as Green List (High Evidence).
Ductal plate malformation v0.56 CC2D2A Ivone Leong Deleted their comment
Ductal plate malformation v0.56 CC2D2A Ivone Leong Added comment: Comment on publications: There are 3 unrelated cases of patients with Meckel syndrome who have variants in the CC2D2A gene.
Ductal plate malformation v0.56 CC2D2A Ivone Leong Publications for gene: CC2D2A were set to 18513680; 19574260; 22246503
Early onset or syndromic epilepsy v0.1145 RAB18 Sarah Leigh Mode of inheritance for gene: RAB18 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1144 RAB18 Sarah Leigh Classified gene: RAB18 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1144 RAB18 Sarah Leigh Gene: rab18 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1143 RAB18 Sarah Leigh Phenotypes for gene: RAB18 were changed from to Warburg micro syndrome 3, 614222
Early onset or syndromic epilepsy v0.1142 RAB18 Sarah Leigh Publications for gene: RAB18 were set to
Early onset or syndromic epilepsy v0.1141 RAB11B Sarah Leigh Marked gene: RAB11B as ready
Early onset or syndromic epilepsy v0.1141 RAB11B Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 2 variants reported in 5 unrelated cases, of which epileptic seizures were reported in three cases. Protein modeling suggested that both variants alter the GTP/GDP binding pocket and reveal that they both have localization patterns similar to inactive RAB11B (PMID 29106825).
Early onset or syndromic epilepsy v0.1141 RAB11B Sarah Leigh Gene: rab11b has been classified as Green List (High Evidence).
Ductal plate malformation v0.55 TMEM67 Ivone Leong Marked gene: TMEM67 as ready
Ductal plate malformation v0.55 TMEM67 Ivone Leong Added comment: Comment when marking as ready: TMEM67 is a disease causing gene of Meckel syndrome and causes congenital hepatic malformations and fibrosis, which is a phenotype of ductal plate malformation.
Ductal plate malformation v0.55 TMEM67 Ivone Leong Gene: tmem67 has been classified as Green List (High Evidence).
Ductal plate malformation v0.55 TMEM67 Ivone Leong Deleted their comment
Ductal plate malformation v0.55 TMEM67 Ivone Leong Added comment: Comment on publications: There are >3 reported cases of variants in TMEM67 causing congenital hepatic malformations.
Ductal plate malformation v0.55 TMEM67 Ivone Leong Publications for gene: TMEM67 were set to 19058225
Early onset or syndromic epilepsy v0.1141 RAB11B Sarah Leigh Publications for gene: RAB11B were set to
Early onset or syndromic epilepsy v0.1140 RAB11B Sarah Leigh Classified gene: RAB11B as Green List (high evidence)
Early onset or syndromic epilepsy v0.1140 RAB11B Sarah Leigh Gene: rab11b has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1139 QDPR Sarah Leigh Marked gene: QDPR as ready
Early onset or syndromic epilepsy v0.1139 QDPR Sarah Leigh Added comment: Comment when marking as ready: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 16 variants reported as in unrelated cases. PMID 26006720 reports seizures in 83% (20 cases) of Hyperphenylalaninemia, BH4-deficient, C, 261630.
Early onset or syndromic epilepsy v0.1139 QDPR Sarah Leigh Gene: qdpr has been classified as Green List (High Evidence).
Ductal plate malformation v0.54 SEC63 Ivone Leong Marked gene: SEC63 as ready
Ductal plate malformation v0.54 SEC63 Ivone Leong Gene: sec63 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1139 QDPR Sarah Leigh Classified gene: QDPR as Green List (high evidence)
Early onset or syndromic epilepsy v0.1139 QDPR Sarah Leigh Gene: qdpr has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1138 QDPR Sarah Leigh Publications for gene: QDPR were set to
Ductal plate malformation v0.54 PRKCSH Ivone Leong Marked gene: PRKCSH as ready
Ductal plate malformation v0.54 PRKCSH Ivone Leong Added comment: Comment when marking as ready: PRKCSH is confirmed as the causative gene for polycystic liver disease 1 on OMIM and listed as a causative gene in GeneReviews.
Ductal plate malformation v0.54 PRKCSH Ivone Leong Gene: prkcsh has been classified as Green List (High Evidence).
Ductal plate malformation v0.54 PRKCSH Ivone Leong Deleted their comment
Ductal plate malformation v0.54 PRKCSH Ivone Leong Added comment: Comment on publications: Four studies reporting on 6 different patients who have polycystic liver disease with different variants in PRKCSH.
Ductal plate malformation v0.54 PRKCSH Ivone Leong Publications for gene: PRKCSH were set to 12529853
Early onset or syndromic epilepsy v0.1137 QDPR Sarah Leigh Phenotypes for gene: QDPR were changed from to Hyperphenylalaninemia, BH4-deficient, C, 261630
Early onset or syndromic epilepsy v0.1136 QDPR Sarah Leigh Mode of inheritance for gene: QDPR was changed from to BIALLELIC, autosomal or pseudoautosomal
Ductal plate malformation v0.53 B9D1 Ivone Leong Marked gene: B9D1 as ready
Ductal plate malformation v0.53 B9D1 Ivone Leong Added comment: Comment when marking as ready: There is not enough evidence to promote B9D1 to a green gene on this panel.
Ductal plate malformation v0.53 B9D1 Ivone Leong Gene: b9d1 has been classified as Amber List (Moderate Evidence).
Ductal plate malformation v0.53 B9D1 Ivone Leong Classified gene: B9D1 as Amber List (moderate evidence)
Ductal plate malformation v0.53 B9D1 Ivone Leong Added comment: Comment on list classification: Demoted from green to amber after taking into consideration the red review by Bill Griffiths (Cambridge University Hospitals) and other sources of evidence. There is not enough evidence from patient data and B9D1 is a red gene on the Rare cilipathy panel.
Ductal plate malformation v0.53 B9D1 Ivone Leong Gene: b9d1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1135 PTS Sarah Leigh Marked gene: PTS as ready
Early onset or syndromic epilepsy v0.1135 PTS Sarah Leigh Gene: pts has been classified as Green List (High Evidence).
Ductal plate malformation v0.52 B9D1 Ivone Leong Publications for gene: B9D1 were set to
Intellectual disability v2.555 COG6 Konstantinos Varvagiannis gene: COG6 was added
gene: COG6 was added to Intellectual disability. Sources: Literature,Expert Review
Mode of inheritance for gene: COG6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COG6 were set to 26260076; 20605848; 23430903; 23606727; 28139241; 28742265; 29445937; 29709711
Phenotypes for gene: COG6 were set to Congenital disorder of glycosylation, type IIl, 614576; Shaheen syndrome, 615328
Penetrance for gene: COG6 were set to Complete
Review for gene: COG6 was set to GREEN
gene: COG6 was marked as current diagnostic
Added comment: DD/ID is an almost universal feature of individuals with biallelic COG6 mutations, whether this is associated with a type II transferrin IEF pattern (as in Congenital disorder of glycosylation, type IIl, 614576) or not (as in Shaheen syndrome, 615328).

More than 15 patients from several different families have been reported to date.

PMID: 26260076 is a collaborative study reporting on new patients as well as on individuals previously described up to 2015 by Lubbehusen et al. (2010 - PMID: 20605848), Huybrechts et al. (2012 - PMID: 23430903) as well as Shaheen et al. (2013 - PMID: 23606727).

As summarized in table 1 of this article, developmental disability was a feature in 8/10, although for a further 2/10 this was probably not relevant (both deceased too early).

The following articles are additional reports although there might be some overlap (applicable for the Saudi patients) : PMIDs: 28139241 (individuals with diagnosis of CDG from Spain), 28742265 (cohort of CDG patients from Saudi Arabia), 29445937 (case report of Saudi subject), 29709711 (Chinese individual with COG6-CDG).

All types of variants have been observed including missense, stopgain and frameshift ones, as well as variants leading to aberrant splicing [eg. positions -2, -9, -24]. The deep intronic variant (position -24) in the individuals reported by Shaheen and others is considered a founder mutation in the Saudi population.

Individuals homozygous for the latter variant have detectable levels of the normal transcript, although 75% of the produced transcript (upon RT-PCR analysis) correspond to retention of 37 intronic nucleotides leading to frameshift and introduction of a premature stop codon. This was also confirmed with Western blot.

Given the detectable levels of the normal transcript, it has been proposed that Shaheen syndrome represents the mildest end of the spectrum COG6-related disorders.

COG6 is included in gene panels for intellectual disability offered by different diagnostic laboratories.

As a result this gene can be considered for inclusion in this panel as green.
Sources: Literature, Expert Review
Early onset or syndromic epilepsy v0.1135 PTS Sarah Leigh Classified gene: PTS as Green List (high evidence)
Early onset or syndromic epilepsy v0.1135 PTS Sarah Leigh Gene: pts has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1134 PTS Sarah Leigh Publications for gene: PTS were set to 11916314; 16364672
Ductal plate malformation v0.51 DGUOK Ivone Leong Marked gene: DGUOK as ready
Ductal plate malformation v0.51 DGUOK Ivone Leong Added comment: Comment when marking as ready: DGUOK is a disease causing gene of DPM
Ductal plate malformation v0.51 DGUOK Ivone Leong Gene: dguok has been classified as Green List (High Evidence).
Ductal plate malformation v0.51 DGUOK Ivone Leong Added comment: Comment on publications: Added another publication (PMID:26874653) provided by Bill Griffiths (Cambridge University Hospitals). The paper reported on 2 families with 3 individuals who have the same variant in the DGUOK gene. The affected patients had protal hypertension without advanced fibrosis/cirrhosis.
Ductal plate malformation v0.51 DGUOK Ivone Leong Publications for gene: DGUOK were set to 30234759; 17073823
Ductal plate malformation v0.50 CC2D2A Ivone Leong Marked gene: CC2D2A as ready
Ductal plate malformation v0.50 CC2D2A Ivone Leong Added comment: Comment when marking as ready: CC2D2A is a disease causing gene of DPM
Ductal plate malformation v0.50 CC2D2A Ivone Leong Gene: cc2d2a has been classified as Green List (High Evidence).
Ductal plate malformation v0.50 CC2D2A Ivone Leong Phenotypes for gene: CC2D2A were changed from Joubert syndrome 9 (612285); Meckel syndrome 6 (612284); COACH syndrome (216360) to Joubert syndrome 9 (612285); Meckel syndrome 6 (612284); COACH syndrome (216360); congenital hepatic fibrosis
Ductal plate malformation v0.49 TMEM67 Ivone Leong Marked gene: TMEM67 as ready
Ductal plate malformation v0.49 TMEM67 Ivone Leong Added comment: Comment when marking as ready: TMEM67 is a disease causing gene of DPM
Ductal plate malformation v0.49 TMEM67 Ivone Leong Gene: tmem67 has been classified as Green List (High Evidence).
Ductal plate malformation v0.49 TMEM67 Ivone Leong Phenotypes for gene: TMEM67 were changed from Meckel syndrome 3 (607361); Nephronophthisis 11 (613550); Joubert syndrome 6 (310688); {Bardet-Biedl syndrome 14, modifier of} (615991); COACH syndrome (216360) to Meckel syndrome 3 (607361); Nephronophthisis 11 (613550); Joubert syndrome 6 (310688); {Bardet-Biedl syndrome 14, modifier of} (615991); COACH syndrome (216360); congenital hepatic fibrosis
Ductal plate malformation v0.48 TMEM67 Ivone Leong Publications for gene: TMEM67 were set to
Ductal plate malformation v0.47 SEC63 Ivone Leong Marked gene: SEC63 as ready
Ductal plate malformation v0.47 SEC63 Ivone Leong Added comment: Comment when marking as ready: SEC63 is a disease causing gene of DPM
Ductal plate malformation v0.47 SEC63 Ivone Leong Gene: sec63 has been classified as Green List (High Evidence).
Ductal plate malformation v0.47 SEC63 Ivone Leong Publications for gene: SEC63 were set to
Ductal plate malformation v0.46 SEC63 Ivone Leong Mode of inheritance for gene: SEC63 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ductal plate malformation v0.45 PRKCSH Ivone Leong Marked gene: PRKCSH as ready
Ductal plate malformation v0.45 PRKCSH Ivone Leong Added comment: Comment when marking as ready: PRKCSH is confirmed as the causative gene for polycystic liver disease 1 on OMIM and listed as a causative gene in GeneReviews.
Ductal plate malformation v0.45 PRKCSH Ivone Leong Gene: prkcsh has been classified as Green List (High Evidence).
Ductal plate malformation v0.45 PRKCSH Ivone Leong Publications for gene: PRKCSH were set to
Early onset or syndromic epilepsy v0.1133 EIF2B5 Rebecca Foulger Publications for gene: EIF2B5 were set to 17646634; 21484434; 15136690; 29995139
Ductal plate malformation v0.44 PRKCSH Ivone Leong Mode of inheritance for gene: PRKCSH was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ductal plate malformation v0.43 PKHD1 Ivone Leong Marked gene: PKHD1 as ready
Ductal plate malformation v0.43 PKHD1 Ivone Leong Added comment: Comment when marking as ready: PKHD1 is a disease causing gene of DPM
Ductal plate malformation v0.43 PKHD1 Ivone Leong Gene: pkhd1 has been classified as Green List (High Evidence).
Ductal plate malformation v0.43 PKHD1 Ivone Leong Added comment: Comment on mode of inheritance: Changed from Biallelic to Both monoallelic and biallelic as a paper provided by Bill Griffiths (Cambridge University Hospitals) reported 2 probands who have Ductal plate malformation with different heterozygous variants (1 a small deletion and another a missense variant) in the PKHD1 gene
Ductal plate malformation v0.43 PKHD1 Ivone Leong Mode of inheritance for gene: PKHD1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1132 EIF2B5 Rebecca Foulger Publications for gene: EIF2B5 were set to 17646634; 21484434; 15136690
Ductal plate malformation v0.42 PKHD1 Ivone Leong Publications for gene: PKHD1 were set to
Early onset or syndromic epilepsy v0.1131 EIF2B1 Rebecca Foulger Publications for gene: EIF2B1 were set to
Early onset or syndromic epilepsy v0.1130 EIF2B1 Rebecca Foulger commented on gene: EIF2B1: In a 2-year-old Chinese girl (case 29) with MIM:603896, Zhang et al. (2015, PMID:25761052) identified a homozygous c(c.328A-G, NM_001414) in exon 4 of the EIF2B1 gene (KL110E). The patient had seizures.
Early onset or syndromic epilepsy v0.1130 EIF2B1 Rebecca Foulger commented on gene: EIF2B1
Ductal plate malformation v0.41 PKD2 Ivone Leong Marked gene: PKD2 as ready
Ductal plate malformation v0.41 PKD2 Ivone Leong Added comment: Comment when marking as ready: PKD2 is on the Eligibility statement
Ductal plate malformation v0.41 PKD2 Ivone Leong Gene: pkd2 has been classified as Green List (High Evidence).
Ductal plate malformation v0.41 PKD2 Ivone Leong Publications for gene: PKD2 were set to
Early onset or syndromic epilepsy v0.1130 EIF2B1 Rebecca Foulger Mode of inheritance for gene: EIF2B1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1129 EIF2B1 Rebecca Foulger Phenotypes for gene: EIF2B1 were changed from to Leukoencephalopathy with vanishing white matter, 603896
Early onset or syndromic epilepsy v0.1128 EARS2 Rebecca Foulger Marked gene: EARS2 as ready
Early onset or syndromic epilepsy v0.1128 EARS2 Rebecca Foulger Gene: ears2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1128 EARS2 Rebecca Foulger Classified gene: EARS2 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1128 EARS2 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Green review from Zornitza plus sufficient cases (>3) of seizures and/or epilepsy in patients from the literature (PMIDs:22492562, 26619324, 27117034, 27206875) for inclusion on panel.
Early onset or syndromic epilepsy v0.1128 EARS2 Rebecca Foulger Gene: ears2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1127 EARS2 Rebecca Foulger Publications for gene: EARS2 were set to
Early onset or syndromic epilepsy v0.1126 EARS2 Rebecca Foulger Phenotypes for gene: EARS2 were changed from Combined oxidative phosphorylation deficiency 12, 614924; Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL) to Combined oxidative phosphorylation deficiency 12, 614924; Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL); Drug-refractory seizures; Epilepsy
Early onset or syndromic epilepsy v0.1125 EARS2 Rebecca Foulger commented on gene: EARS2
Early onset or syndromic epilepsy v0.1125 EARS2 Rebecca Foulger Phenotypes for gene: EARS2 were changed from Combined oxidative phosphorylation deficiency 12, 614924 to Combined oxidative phosphorylation deficiency 12, 614924; Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL)
Ductal plate malformation v0.40 PKD1 Ivone Leong Marked gene: PKD1 as ready
Ductal plate malformation v0.40 PKD1 Ivone Leong Added comment: Comment when marking as ready: PKD1 is on the Eligibility statement
Ductal plate malformation v0.40 PKD1 Ivone Leong Gene: pkd1 has been classified as Green List (High Evidence).
Ductal plate malformation v0.40 PKD1 Ivone Leong Publications for gene: PKD1 were set to
Ductal plate malformation v0.39 LRP5 Ivone Leong Marked gene: LRP5 as ready
Ductal plate malformation v0.39 LRP5 Ivone Leong Added comment: Comment when marking as ready: LRP5 is a disease causing gene of DPM
Ductal plate malformation v0.39 LRP5 Ivone Leong Gene: lrp5 has been classified as Green List (High Evidence).
Ductal plate malformation v0.39 LRP5 Ivone Leong Publications for gene: LRP5 were set to
Ductal plate malformation v0.38 GANAB Ivone Leong Marked gene: GANAB as ready
Ductal plate malformation v0.38 GANAB Ivone Leong Added comment: Comment when marking as ready: GANAB is a disease causing gene of DPM
Ductal plate malformation v0.38 GANAB Ivone Leong Gene: ganab has been classified as Green List (High Evidence).
Ductal plate malformation v0.38 ALG8 Ivone Leong Marked gene: ALG8 as ready
Ductal plate malformation v0.38 ALG8 Ivone Leong Added comment: Comment when marking as ready: ALG is a disease causing gene of DPM.
Ductal plate malformation v0.38 ALG8 Ivone Leong Gene: alg8 has been classified as Green List (High Evidence).
Ductal plate malformation v0.38 GANAB Ivone Leong Publications for gene: GANAB were set to
Ductal plate malformation v0.37 GANAB Ivone Leong Mode of inheritance for gene: GANAB was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ductal plate malformation v0.36 ALG8 Ivone Leong Publications for gene: ALG8 were set to
Early onset or syndromic epilepsy v0.1124 EARS2 Rebecca Foulger Mode of inheritance for gene: EARS2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1123 EARS2 Rebecca Foulger Phenotypes for gene: EARS2 were changed from to Combined oxidative phosphorylation deficiency 12, 614924
Early onset or syndromic epilepsy v0.1122 DYNC1H1 Rebecca Foulger Marked gene: DYNC1H1 as ready
Early onset or syndromic epilepsy v0.1122 DYNC1H1 Rebecca Foulger Gene: dync1h1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1122 DYNC1H1 Rebecca Foulger Classified gene: DYNC1H1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1122 DYNC1H1 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Green review by Zornitza and sufficient unrelated cases (7 sporadic cases plus two brothers and their mother) in PMID:23603762 of patients with epilepsy for inclusion on panel.
Early onset or syndromic epilepsy v0.1122 DYNC1H1 Rebecca Foulger Gene: dync1h1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1121 DYNC1H1 Rebecca Foulger Phenotypes for gene: DYNC1H1 were changed from Mental retardation, autosomal dominant 13, 614563; Lennox Gastaut; Early-onset epilepsy; Late-onset epilepsy; Focal seizures to Mental retardation, autosomal dominant 13, 614563; malformations of cortical development (MCD); Lennox Gastaut; Early-onset epilepsy; Late-onset epilepsy; Focal seizures
Early onset or syndromic epilepsy v0.1120 DYNC1H1 Rebecca Foulger Phenotypes for gene: DYNC1H1 were changed from Mental retardation, autosomal dominant 13, 614563 to Mental retardation, autosomal dominant 13, 614563; Lennox Gastaut; Early-onset epilepsy; Late-onset epilepsy; Focal seizures
Early onset or syndromic epilepsy v0.1119 DYNC1H1 Rebecca Foulger commented on gene: DYNC1H1
Early onset or syndromic epilepsy v0.1119 DYNC1H1 Rebecca Foulger Mode of inheritance for gene: DYNC1H1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v0.1118 DYNC1H1 Rebecca Foulger Publications for gene: DYNC1H1 were set to
Early onset or syndromic epilepsy v0.1117 DYNC1H1 Rebecca Foulger Phenotypes for gene: DYNC1H1 were changed from to Mental retardation, autosomal dominant 13, 614563
Early onset or syndromic epilepsy v0.1116 DPM1 Rebecca Foulger Marked gene: DPM1 as ready
Early onset or syndromic epilepsy v0.1116 DPM1 Rebecca Foulger Gene: dpm1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1116 DPM1 Rebecca Foulger Added comment: Comment on publications: Epilepsy is not reported in all patients. Severe epilepsy was not present in 2 French siblings with CDG1E, born of consanguineous Algerian parents, as reported Dancourt et al. (2006, PMID:16641202).
Early onset or syndromic epilepsy v0.1116 DPM1 Rebecca Foulger Publications for gene: DPM1 were set to 23856421; 10642597; 10642602
Early onset or syndromic epilepsy v0.1115 DPM1 Rebecca Foulger Classified gene: DPM1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1115 DPM1 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Green review by Zornitza. Confirmed DD-G2P gene for congenital disorder of glycosylation, which can present with seizures. Sufficient cases of seizures in patients with CDG1E (MIM:608799) for inclusion on panel: 4 unrelated cases in PMIDs 23856421, 10642597 and 10642602, several of which are compound heterozygous for a substitution AND a deletion in DPM1.
Early onset or syndromic epilepsy v0.1115 DPM1 Rebecca Foulger Gene: dpm1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1114 DPM1 Rebecca Foulger Publications for gene: DPM1 were set to
Early onset or syndromic epilepsy v0.1113 DPM1 Rebecca Foulger commented on gene: DPM1: Imbach et al. (2000, PMID:10642602) report a brother and sister with severe developmental delay, repeated seizures, and dysmorphic features. Both sibs were compound heterozygous for the 274C>G (R92G) transversion and a 628delC deletion in DPM1.
Early onset or syndromic epilepsy v0.1113 DPM1 Rebecca Foulger commented on gene: DPM1: Kim et al., 2000 (PMID:10642597) report a patient with CDG1E and a homozygous 274C-G transversion in the DPM1 gene (p.R92G). Another unrelated patient was compound heterozygous for the R92G variant and a 13-bp deletion in exon 4 that may result in an unstable transcript. Both patients were recorded with medically intractable seizures
Early onset or syndromic epilepsy v0.1113 DPM1 Rebecca Foulger commented on gene: DPM1
Early onset or syndromic epilepsy v0.1113 DPM1 Rebecca Foulger Mode of inheritance for gene: DPM1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1112 DPM1 Rebecca Foulger Phenotypes for gene: DPM1 were changed from to Congenital disorder of glycosylation, type Ie, 608799
Early onset or syndromic epilepsy v0.1111 TELO2 Konstantinos Varvagiannis reviewed gene: TELO2: Rating: AMBER; Mode of pathogenicity: None; Publications: 27132593, 28944240; Phenotypes: You-Hoover-Fong syndrome, MIM 616954; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1111 TELO2 Konstantinos Varvagiannis Deleted their review
Early onset or syndromic epilepsy v0.1111 TELO2 Konstantinos Varvagiannis gene: TELO2 was added
gene: TELO2 was added to Genetic epilepsy syndromes. Sources: Literature,Expert Review
Mode of inheritance for gene: TELO2 was set to BIALLELIC, autosomal or pseudoautosomal
Penetrance for gene: TELO2 were set to Complete
Added comment: Biallelic mutations in TELO2 cause You-Hoover-Fong syndrome (MIM 616954). //

PMID: 27132593 reports on 6 patients (from 4 non-consanguineous families) with biallelic TELO2 variants and a similar phenotype.

Intellectual disability and microcephaly were universal features (6/6). Abnormal hearing (3/6), cortical visual impairment (3/6), abnormality of the cardiovascular system (3/6), behavioral problems (laughter outbursts in 3/6) and abnormal balance and movement disorder (6/6) were part of the phenotype. One individual had seizures.

5 missense variants and a complex allele with a stopgain variant localized in cis with a splice-site variant (NM_016111.3:c.514C>T or p.Gln172* in cis with c.2034+1G>A) are reported.

As a result heterozygosity for the complex variant may be confounded with compound heterozygous state until segregation studies are performed.

Functional studies support pathogenicity of the missense variants (reduced protein steady-state levels of TELO2 as well as TTI1 and TTI2 - the 2 other members of the TTT complex) suggesting loss of function.

PMID: 28944240 reports on 2 sisters born to non-consanguineous parents. Both were compound heterozygous for 2 novel variants, a missense and a frameshift one. Severe microcephaly (-8.5 SD and -10.7 SD) and seizures were noted in both. The first sister passed away at the age of 2 months due to a respiratory infection. The other sister demonstrated a compatible, though much more severe phenotype (ID and microcephaly) with additional features (dwarfism, renal anomalies, retinitis pigmentosa, etc) compared to previously reported patients. //

As a result this gene could possibly be considered for inclusion in this panel as amber (seizures in 3/8 patients reported to date - these individuals belonged to 2 different families) .
Sources: Literature, Expert Review
Intellectual disability v2.555 TELO2 Konstantinos Varvagiannis gene: TELO2 was added
gene: TELO2 was added to Intellectual disability. Sources: Literature,Expert Review
Mode of inheritance for gene: TELO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TELO2 were set to 27132593; 28944240
Phenotypes for gene: TELO2 were set to You-Hoover-Fong syndrome, MIM 616954
Penetrance for gene: TELO2 were set to Complete
Review for gene: TELO2 was set to GREEN
gene: TELO2 was marked as current diagnostic
Added comment: Biallelic mutations in TELO2 cause You-Hoover-Fong syndrome (MIM 616954). //

PMID: 27132593 reports on 6 patients (from 4 non-consanguineous families) with biallelic TELO2 variants and a similar phenotype.

Intellectual disability and microcephaly were universal features (6/6). Abnormal hearing (3/6), cortical visual impairment (3/6), abnormality of the cardiovascular system (3/6), behavioral problems (laughter outbursts in 3/6) and abnormal balance and movement disorder (6/6) were part of the phenotype. One individual had seizures.

5 missense variants and a complex allele with a stopgain variant localized in cis with a splice-site variant (NM_016111.3:c.514C>T or p.Gln172* in cis with c.2034+1G>A) are reported.

As a result heterozygosity for the complex variant may be confounded with compound heterozygous state until segregation studies are performed.

Functional studies support pathogenicity of the missense variants (reduced protein steady-state levels of TELO2 as well as TTI1 and TTI2 - the 2 other members of the TTT complex) suggesting loss of function.

PMID: 28944240 reports on 2 sisters born to non-consanguineous parents. Both were compound heterozygous for 2 novel variants, a missense and a frameshift one. Severe microcephaly (-8.5 SD and -10.7 SD) and seizures were noted in both. The first sister passed away at the age of 2 months due to a respiratory infection. The other sister demonstrated a compatible, though much more severe phenotype (of ID, dwarfism, retinitis pigmentosa, etc) compared to previously reported patients. //

Biallelic mutations in TTI2 (of the same complex) lead to similar phenotypes (gene rated green in the ID panel). //

TELO2 is included in gene panels for intellectual disability offered by different diagnostic laboratories. //

As a result this gene can be considered for inclusion in this panel as green.
Sources: Literature, Expert Review
Intellectual disability v2.555 TTI2 Konstantinos Varvagiannis Deleted their review
Intellectual disability v2.555 TTI2 Konstantinos Varvagiannis reviewed gene: TTI2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23956177; Phenotypes: ; Mode of inheritance: None
Ductal plate malformation v0.35 PKD1 Bill Griffiths edited their review of gene: PKD1: Changed publications: PMID: 3178424 PMID: 9211343; Changed phenotypes: Polycystic liver, polycystic kidney, Caroli's disease
Ductal plate malformation v0.35 OFD1 Bill Griffiths reviewed gene: OFD1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 20818665; Phenotypes: biliary dysplasia; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ductal plate malformation v0.35 B9D1 Bill Griffiths reviewed gene: B9D1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 21763481; Phenotypes: Ductal plate malformation; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ductal plate malformation v0.35 RPGRIP1L Bill Griffiths reviewed gene: RPGRIP1L: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19574260; Phenotypes: Congenital hepatic fibrosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ductal plate malformation v0.35 NPHP3 Bill Griffiths edited their review of gene: NPHP3: Changed publications: PMID: 12872122, PMID: 20007846, PMID 21845392; Changed phenotypes: Congenital hepatic fibrosis, Caroli's disease
Ductal plate malformation v0.35 PKHD1 Bill Griffiths edited their review of gene: PKHD1: Changed publications: PMID: 11919560 PMID: 30211211; Changed phenotypes: Polycystic kidney, liver cysts, congenital hepatic fibrosis, Caroli's disease, biliary dysplasia
Ductal plate malformation v0.35 NPHP3 Bill Griffiths reviewed gene: NPHP3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 12872122, PMID: 20007846; Phenotypes: Congenital hepatic fibrosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ductal plate malformation v0.35 CC2D2A Bill Griffiths reviewed gene: CC2D2A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19574260; Phenotypes: Congenital hepatic fibrosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ductal plate malformation v0.35 DGUOK Bill Griffiths edited their review of gene: DGUOK: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ductal plate malformation v0.35 KCNN3 Bill Griffiths edited their review of gene: KCNN3: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ductal plate malformation v0.35 TMEM67 Bill Griffiths reviewed gene: TMEM67: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 19058225; Phenotypes: congenital hepatic fibrosis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ductal plate malformation v0.35 KCNN3 Bill Griffiths gene: KCNN3 was added
gene: KCNN3 was added to Polycystic liver disease. Sources: Literature
Mode of inheritance for gene: KCNN3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNN3 were set to PMID: 26658685
Phenotypes for gene: KCNN3 were set to portal hypertension; varices; splenomegaly
Penetrance for gene: KCNN3 were set to unknown
Review for gene: KCNN3 was set to GREEN
Added comment: Sources: Literature
Ductal plate malformation v0.35 DGUOK Bill Griffiths reviewed gene: DGUOK: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 26874653; Phenotypes: portal hypertension, varices, splenomegaly; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ductal plate malformation v0.35 SEC63 Bill Griffiths reviewed gene: SEC63: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 15133510; Phenotypes: Polycystic liver; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ductal plate malformation v0.35 PRKCSH Bill Griffiths reviewed gene: PRKCSH: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 12529853; Phenotypes: Polycystic liver, kidney cysts, pancreatic cysts; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ductal plate malformation v0.35 PKHD1 Bill Griffiths reviewed gene: PKHD1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 11919560; Phenotypes: Polycystic kidney, liver cysts, congenital hepatic fibrosis, Caroli's disease; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ductal plate malformation v0.35 PKD2 Bill Griffiths reviewed gene: PKD2: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 29321346; Phenotypes: Polycystic kidney disease, liver cysts; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ductal plate malformation v0.35 PKD1 Bill Griffiths reviewed gene: PKD1: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 3178424; Phenotypes: Polycystic liver, polycystic kidney; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ductal plate malformation v0.35 LRP5 Bill Griffiths reviewed gene: LRP5: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 24706814; Phenotypes: Polycystic liver, renal cysts; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ductal plate malformation v0.35 GANAB Bill Griffiths reviewed gene: GANAB: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 29243290, PMID: 27259053; Phenotypes: Polycystic liver, polycystic kidney; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ductal plate malformation v0.35 ALG8 Bill Griffiths reviewed gene: ALG8: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 28375157; Phenotypes: Polycystic liver disease, renal cysts; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v2.555 BRD4 Konstantinos Varvagiannis gene: BRD4 was added
gene: BRD4 was added to Intellectual disability. Sources: Literature,Expert Review
Mode of inheritance for gene: BRD4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: BRD4 were set to 29379197; 30055032; 30302754
Phenotypes for gene: BRD4 were set to Intellectual disability; Microcephaly; Abnormal heart morphology; Abnormality of the face
Penetrance for gene: BRD4 were set to unknown
Review for gene: BRD4 was set to GREEN
gene: BRD4 was marked as current diagnostic
Added comment: PMID: 29379197 reports on 3 unrelated individuals with de novo mutations in BRD4 and a Cornelia de Lange-like phenotype. One of these individuals was a DDD study participant (DDD4K.04273). A further (fourth) individual had a 1.04 Mb deletion encompassing BRD4 (and 28 other genes) and presented with a similar phenotype.

Appart from intellectual disability which was a universal feature common features included a CdLS-like appearance (3/4), microcephaly (3/4) and cardiac malformations (VSD in 2/4).

Review of published patients with multigenic deletions spanning also BRD4 support a CdLS-like phenotype as well as haploinsufficiency as the underlying mechanism.

As the authors note, mice heterozygous for loss-of-function mutations in BRD4 show CdLS like features.
Functional studies performed demonstrated association of BRD4 with NIPBL with colocalization (/shared binding) to super-enhancers and co-regulation of gene expression.

The variants reported in this study included a missense as well as 2 frameshift mutations.

PMIDs: 30055032 and 30302754 report further patients with deletions spanning BRD4 and review the previously published patients.

BRD4 is included in gene panels for intellectual disability offered by different diagnostic laboratories.

As a result this gene can be considered for inclusion in this panel as green.
Sources: Literature, Expert Review
Early onset or syndromic epilepsy v0.1111 DPAGT1 Rebecca Foulger Marked gene: DPAGT1 as ready
Early onset or syndromic epilepsy v0.1111 DPAGT1 Rebecca Foulger Gene: dpagt1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1111 DPAGT1 Rebecca Foulger Classified gene: DPAGT1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1111 DPAGT1 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Green review. Confirmed DD-G2P gene for Congenital disorder of glycosylation (CDG), which can present with seizures. Sufficient cases of seizures from the literature (3 cases from PMIDs:22304930, 23249953, 12872255) for inclusion on panel.
Early onset or syndromic epilepsy v0.1111 DPAGT1 Rebecca Foulger Gene: dpagt1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1110 DPAGT1 Rebecca Foulger commented on gene: DPAGT1: In a patient with central disorder of glycosylation type Ij, Wu et al. (2003, PMID:12872255) identified reduced DPAGT1 enzymatic activity. In the paternal allele, a variant Y170C was identified. Although no variant was identified in the maternal allele, it produced only 12% of the normal amount of mRNA. She had severe hypotonia and medically intractable seizures amongst her phenotypes.
Early onset or syndromic epilepsy v0.1110 DPAGT1 Rebecca Foulger commented on gene: DPAGT1: In a Pakistani brother and sister born of unrelated patients with a mild form of CDG Ij, Iqbal et al. (2013, PMID:23249953) identified compound heterozygous mutations in the DPAGT1 gene (I29F and L168P). The patients had normal psychomotor development until ages 2 and 5 years, respectively, when they both developed seizures, hypotonia, and aggressive behavior. Seizures and additional phenotypes continued into adulthood.
Early onset or syndromic epilepsy v0.1110 DPAGT1 Rebecca Foulger commented on gene: DPAGT1
Hypophosphataemia or rickets v0.3 SLC34A3 Sian Ellard reviewed gene: SLC34A3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Hypophosphataemia or rickets v0.3 FGF23 Sian Ellard reviewed gene: FGF23: Rating: GREEN; Mode of pathogenicity: None; Publications: 11062477; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Hypophosphataemia or rickets v0.3 ENPP1 Sian Ellard reviewed gene: ENPP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20137773; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Hypophosphataemia or rickets v0.3 DMP1 Sian Ellard reviewed gene: DMP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 17033625; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Hypophosphataemia or rickets v0.3 PHEX Sian Ellard reviewed gene: PHEX: Rating: GREEN; Mode of pathogenicity: None; Publications: 7550339, 9106524, 19219621; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males); Current diagnostic: yes
Early onset or syndromic epilepsy v0.1110 HCN2 Ivone Leong Classified gene: HCN2 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1110 HCN2 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. No phenotypes have been associated with HCN2 in OMIM or Gene2Phenotype. There are 2 papers (PMID: 29064616, 17931874) reporting misssense, frameshift and small deletion variants in HCN2 associated with Genetic epilepsy with febrile seizures plus disorders and other epilepsy/seizure disorders (e.g. Idiopathic generalized epilepsy). There is also evidence that these variants cause gain-of-function effects (PMID: 29064616). Another study reported on a patient with sporadic idiopathic generalised seizures who had a recessive loss-of-function missense variant. An HCN2 knockout mouse model (PMID: 12514127) had absence seizures.
Early onset or syndromic epilepsy v0.1110 HCN2 Ivone Leong Gene: hcn2 has been classified as Green List (High Evidence).
Intellectual disability v2.555 ATP8A2 Konstantinos Varvagiannis reviewed gene: ATP8A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22892528, 27679995, 30012219, 29531481; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Early onset or syndromic epilepsy v0.1109 HCN2 Ivone Leong Phenotypes for gene: HCN2 were changed from Genetic epilepsy with efbrile seizures plus; Other seizure disorders to Genetic epilepsy with febrile seizures plus; Other seizure disorders
Early onset or syndromic epilepsy v0.1108 HCN2 Ivone Leong Phenotypes for gene: HCN2 were changed from to Genetic epilepsy with efbrile seizures plus; Other seizure disorders
Early onset or syndromic epilepsy v0.1107 HCN2 Ivone Leong Mode of inheritance for gene: HCN2 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1106 HCN2 Ivone Leong Publications for gene: HCN2 were set to 29064616; 20437590; 12514127; 17931874
Early onset or syndromic epilepsy v0.1105 HCN2 Ivone Leong Publications for gene: HCN2 were set to
Early onset or syndromic epilepsy v0.1104 GPHN Ivone Leong Marked gene: GPHN as ready
Early onset or syndromic epilepsy v0.1104 GPHN Ivone Leong Added comment: Comment when marking as ready: Gene is ready as there is enough evidence. All cases were selected based on the fact that patients were diagnosed with Molybdenum cofactor deficiency C or are positive for molybdenum cofactor deficiency who have a causative variant in the GPHN gene, who also have seizures. This is why PMID: 24561070, 23393157 were not included as publication sources.
Early onset or syndromic epilepsy v0.1104 GPHN Ivone Leong Gene: gphn has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1104 GPHN Ivone Leong Classified gene: GPHN as Green List (high evidence)
Early onset or syndromic epilepsy v0.1104 GPHN Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. GPHN is confirmed to be associated with Molybdenum cofactor deficiency C on OMIM, with seizures listed as a phenotype; however, there is nothing listed in Gene2Phenotype.
There are 3 papers (PMID: 26613940,12684523,11095995) reporting patients who have Molybdenum cofactor deficiency C with different variants in the GPHN gene. All of these patients are of different ethnicity and all have seizures.
Early onset or syndromic epilepsy v0.1104 GPHN Ivone Leong Gene: gphn has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1103 GPHN Ivone Leong Publications for gene: GPHN were set to
Early onset or syndromic epilepsy v0.1102 MED12 Ivone Leong commented on gene: MED12
Early onset or syndromic epilepsy v0.1102 MED12 Ivone Leong Publications for gene: MED12 were set to
Early onset or syndromic epilepsy v0.1101 MED12 Ivone Leong Phenotypes for gene: MED12 were changed from Lujan-Fryns syndrome, 309520 to Lujan-Fryns syndrome, 309520; Opitz-Kaveggia syndrome, 305450
Early onset or syndromic epilepsy v0.1100 MED12 Ivone Leong Mode of inheritance for gene: MED12 was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early onset or syndromic epilepsy v0.1099 MED12 Ivone Leong Phenotypes for gene: MED12 were changed from to Lujan-Fryns syndrome, 309520
Early onset or syndromic epilepsy v0.1098 MAP2K2 Ivone Leong Marked gene: MAP2K2 as ready
Early onset or syndromic epilepsy v0.1098 MAP2K2 Ivone Leong Gene: map2k2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1098 MAP2K2 Ivone Leong Classified gene: MAP2K2 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1098 MAP2K2 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. MAP2K2 is confirmed to be associated with Cardiofaciocutaneous syndrome 4 in both OMIM and Gene2Phenotype. Only Gene2Phenotype lists seizures as a phenotype.
There are three reported cases (PMID: 29799162, 24719372, 27799067)
of unrelated probands with different variants (2 missense and one deletion) who have seizures. It should be noted that not all patients with a MAP2K2 variant experience seizures.
Early onset or syndromic epilepsy v0.1098 MAP2K2 Ivone Leong Gene: map2k2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1097 MAP2K2 Ivone Leong Publications for gene: MAP2K2 were set to 29799162; 2471937; 27799067
Early onset or syndromic epilepsy v0.1096 MAP2K2 Ivone Leong Publications for gene: MAP2K2 were set to
Early onset or syndromic epilepsy v0.1095 MACF1 Konstantinos Varvagiannis gene: MACF1 was added
gene: MACF1 was added to Genetic epilepsy syndromes. Sources: Literature,Expert Review
Mode of inheritance for gene: MACF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MACF1 were set to Intellectual disability; Seizures; Lissencephaly; Brainstem dysplasia
Penetrance for gene: MACF1 were set to unknown
Mode of pathogenicity for gene: MACF1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: MACF1 was set to GREEN
Added comment: Dobyns et al. (doi.org/10.1016/j.ajhg.2018.10.019) report on 9 individuals (all unrelated appart from a pair of monozygotic twins) with de novo variants in MACF1.

All patients presented lissencephaly and brainstem hypoplasia with associated intellectual disability (9/9) and seizures (9/9).

Seven of these individuals had de novo missense variants within the GAR domain and an eighth had a deletion of several exons also spanning this domain and leading to an in-frame deletion. A further ninth patient had a de novo missense variant in the spectrin repeat domain and was found to have similar features although the brainstem dysplasia was rather subtle.

5 missense variants (4 of which in the GAR domain) and an intragenic deletion are reported in total.

The variants in the GAR domain were predicted to have important effect in the zinc-binding pocket. The spectrin repeat (SR4) is thought to have an important role for the function of MACF1 and further to neuronal migration.

Knockdown of Macf1 in mice has been shown to result in developmental defects similar to the human malformation.

The authors note that several high-confidence loss-of-function mutations are listed in ExAC and as a result this type of variants could be non-pathogenic (or lead to neurodevelopmental disorders with reduced penetrance). Still MACF1 has a pLI of 1.0.

As for the missense variants, the authors suggest either a gain-of-function or dominant negative mechanism.

Caution should be taken when interpreting variants as the ENST00000372915.7 (or MACF1-204) transcript is used for the predicted protein changes, although ENST00000361689.6 or MACF1-203 (corresponding to NM_012090.5) has also been used in some tables or figures.

As a result, this gene can be considered for inclusion in this panel probably as green.
Sources: Literature, Expert Review
Intellectual disability v2.555 MACF1 Konstantinos Varvagiannis gene: MACF1 was added
gene: MACF1 was added to Intellectual disability. Sources: Literature,Expert Review
Mode of inheritance for gene: MACF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: MACF1 were set to Intellectual disability; Seizures; Lissencephaly; Brainstem dysplasia
Penetrance for gene: MACF1 were set to unknown
Mode of pathogenicity for gene: MACF1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: MACF1 was set to GREEN
Added comment: Dobyns et al. (doi.org/10.1016/j.ajhg.2018.10.019) report on 9 individuals (all unrelated appart from a pair of monozygotic twins) with de novo variants in MACF1.

All patients presented lissencephaly and brainstem hypoplasia with associated intellectual disability (9/9) and seizures (9/9).

Seven of these individuals had de novo missense variants within the GAR domain and an eighth had a deletion of several exons also spanning this domain and leading to an in-frame deletion. A further ninth patient had a de novo missense variant in the spectrin repeat domain and was found to have similar features although the brainstem dysplasia was rather subtle.

5 missense variants (4 of which in the GAR domain) and an intragenic deletion are reported in total.

The variants in the GAR domain were predicted to have important effect in the zinc-binding pocket. The spectrin repeat (SR4) is thought to have an important role for the function of MACF1 and further to neuronal migration.

Knockdown of Macf1 in mice has been shown to result in developmental defects similar to the human malformation.

The authors note that several high-confidence loss-of-function mutations are listed in ExAC and as a result this type of variants could be non-pathogenic (or lead to neurodevelopmental disorders with reduced penetrance). Still MACF1 has a pLI of 1.0.

As for the missense variants, the authors suggest either a gain-of-function or dominant negative mechanism.

Caution should be taken when interpreting variants as the ENST00000372915.7 (or MACF1-204) transcript is used for the predicted protein changes, although ENST00000361689.6 or MACF1-203 (corresponding to NM_012090.5) has also been used in some tables or figures.

As a result, this gene can be considered for inclusion in this panel probably as green.
Sources: Literature, Expert Review
Early onset or syndromic epilepsy v0.1095 DPAGT1 Rebecca Foulger Mode of inheritance for gene: DPAGT1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1094 DPAGT1 Rebecca Foulger Phenotypes for gene: DPAGT1 were changed from to Congenital disorder of glycosylation, type Ij, 608093
Early onset or syndromic epilepsy v0.1093 DOLK Rebecca Foulger commented on gene: DOLK: Lebfer et al, 2011 (PMID:22242004) say epilepsy was not present in their patients with DOLK variants and dilated cardiomyopathy.
Early onset or syndromic epilepsy v0.1093 DOLK Rebecca Foulger Publications for gene: DOLK were set to 23890587
Early onset or syndromic epilepsy v0.1092 DOLK Rebecca Foulger commented on gene: DOLK: PMID:17273964 (Kranz et al. 2007) report 2 affected first cousins in a consanguineous German family with homozygosity for a 295T-A transversion in the DOLK gene (C99S). For subject GH, seizures due to hypsarrhythmia started at age 7 wk. Subject NB, a first cousin of GH, had no seizures. The authors also report 2 Turkish siblings from consanguineous parents with a 1322A-C transversion in the DOLK gene (Y441S). No epilepsy was mentioned, although death occured age 7 mo and 4 mo.
Early onset or syndromic epilepsy v0.1092 MAP2K2 Ivone Leong Phenotypes for gene: MAP2K2 were changed from to Cardiofaciocutaneous syndrome 4, 615280
Early onset or syndromic epilepsy v0.1091 DOLK Rebecca Foulger Publications for gene: DOLK were set to
Early onset or syndromic epilepsy v0.1090 DOLK Rebecca Foulger commented on gene: DOLK
Early onset or syndromic epilepsy v0.1090 MAP2K1 Ivone Leong Marked gene: MAP2K1 as ready
Early onset or syndromic epilepsy v0.1090 MAP2K1 Ivone Leong Gene: map2k1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1090 MAP2K1 Ivone Leong Classified gene: MAP2K1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1090 MAP2K1 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. Both Omim and Gene2Phenotype confirmed that MAP2K1 is associated with Cardiofaciocutaneous syndrome and seizure is listed as a phenotype by Gene2Phenotype but not OMIM.
A study (PMID: 27862862) reported a proband with a missense variant who has seizures. A large study (PMID: 18039235) examining patients from North America, Australia and UK found that 4 out of 5 patients with different missense variants in MAP2K1 had seizures.
Early onset or syndromic epilepsy v0.1090 MAP2K1 Ivone Leong Gene: map2k1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1089 DOLK Rebecca Foulger Mode of inheritance for gene: DOLK was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1088 DOLK Rebecca Foulger Phenotypes for gene: DOLK were changed from to Congenital disorder of glycosylation, type Im, 610768
Early onset or syndromic epilepsy v0.1087 DNM1L Rebecca Foulger Marked gene: DNM1L as ready
Early onset or syndromic epilepsy v0.1087 DNM1L Rebecca Foulger Gene: dnm1l has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1087 DNM1L Rebecca Foulger Classified gene: DNM1L as Green List (high evidence)
Early onset or syndromic epilepsy v0.1087 DNM1L Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Green rating by Zornitza. At least 3 cases in the literature of unrelated patients with DNM1L variants and seizures (1 in PMID:26604000 and 2 in PMID:27145208).
Early onset or syndromic epilepsy v0.1087 DNM1L Rebecca Foulger Gene: dnm1l has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1086 DNM1L Rebecca Foulger Phenotypes for gene: DNM1L were changed from Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1, 614388 to Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1, 614388; refractory epilepsy; refractory focal status epilepticus
Early onset or syndromic epilepsy v0.1085 DNM1L Rebecca Foulger commented on gene: DNM1L
Early onset or syndromic epilepsy v0.1085 DNM1L Rebecca Foulger Publications for gene: DNM1L were set to 26604000
Early onset or syndromic epilepsy v0.1084 MAP2K1 Ivone Leong Publications for gene: MAP2K1 were set to 18039235
Early onset or syndromic epilepsy v0.1083 DNM1L Rebecca Foulger Publications for gene: DNM1L were set to
Early onset or syndromic epilepsy v0.1082 DNM1L Rebecca Foulger Mode of inheritance for gene: DNM1L was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1081 DNM1L Rebecca Foulger Phenotypes for gene: DNM1L were changed from to Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1, 614388
Early onset or syndromic epilepsy v0.1080 DHCR24 Rebecca Foulger Marked gene: DHCR24 as ready
Early onset or syndromic epilepsy v0.1080 DHCR24 Rebecca Foulger Gene: dhcr24 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1080 DHCR24 Rebecca Foulger Tag watchlist tag was added to gene: DHCR24.
Early onset or syndromic epilepsy v0.1080 DHCR24 Rebecca Foulger commented on gene: DHCR24: Added 'watchlist' tag.
Early onset or syndromic epilepsy v0.1080 DHCR24 Rebecca Foulger Publications for gene: DHCR24 were set to
Early onset or syndromic epilepsy v0.1079 DHCR24 Rebecca Foulger Classified gene: DHCR24 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v0.1079 DHCR24 Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber: Confirmed DD-G2P gene for Desmosterolosis but only 2 families reported so far in the literature with seizures as part of the desmosterolosis phenotype: PMIDs:21559050 and 24961299.
Early onset or syndromic epilepsy v0.1079 DHCR24 Rebecca Foulger Gene: dhcr24 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1078 DHCR24 Rebecca Foulger commented on gene: DHCR24: Epilepsy not reported as part of phenotype in patients from PMID:21671375 (Schaaf et al 2011) and PMID:11519011 (Waterham et al.2001).
Early onset or syndromic epilepsy v0.1078 DHCR24 Rebecca Foulger commented on gene: DHCR24: Dias et al, 2014 report two sisters homozygous for the 571G>A (E191K) DHCR24 variant with syndromic ID and desmosterolosis. Each had transient neonatal seizures. The authors also provide a summary table of 9 patients to-date (2014) with DHCR24 and Desmosterolosis. Only this family and the kindred reported by PMID:21559050 exhibit seizures as part of their phenotype.
Early onset or syndromic epilepsy v0.1078 DHCR24 Rebecca Foulger commented on gene: DHCR24
Early onset or syndromic epilepsy v0.1078 DHCR24 Rebecca Foulger Phenotypes for gene: DHCR24 were changed from to Desmosterolosis, 602398
Early onset or syndromic epilepsy v0.1077 DHCR24 Rebecca Foulger Mode of inheritance for gene: DHCR24 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1076 DENND5A Rebecca Foulger Marked gene: DENND5A as ready
Early onset or syndromic epilepsy v0.1076 DENND5A Rebecca Foulger Gene: dennd5a has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1076 DENND5A Rebecca Foulger Classified gene: DENND5A as Green List (high evidence)
Early onset or syndromic epilepsy v0.1076 DENND5A Rebecca Foulger Gene: dennd5a has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.71 ERLIN1 Alistair Pagnamenta commented on gene: ERLIN1: Novarino et al (2014) reported 7 affected individuals from 3 different consanguineous families had homozygous variants in this gene co-segregating consistent with an AR mode of inheritance. In the first of these families, significant evidence for genetic linkage was identified on 10q (pLOD >3.0) and this region harboured p.R255X (see PMID: 24482476)
Early onset or syndromic epilepsy v0.1075 DENND5A Rebecca Foulger Classified gene: DENND5A as Amber List (moderate evidence)
Early onset or syndromic epilepsy v0.1075 DENND5A Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Although only Probable confidence level in DD-G2P for EPILEPTIC ENCEPHALOPATHY, there are suffcient cases from PMIDs 27866705 and 27431290 (5 individuals from 4 unrelated families) to support gene:disease association and diagnostic rating.
Early onset or syndromic epilepsy v0.1075 DENND5A Rebecca Foulger Gene: dennd5a has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1074 DENND5A Rebecca Foulger Publications for gene: DENND5A were set to
Early onset or syndromic epilepsy v0.1073 DENND5A Rebecca Foulger Mode of inheritance for gene: DENND5A was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1072 DENND5A Rebecca Foulger commented on gene: DENND5A
Early onset or syndromic epilepsy v0.1072 DENND5A Rebecca Foulger Phenotypes for gene: DENND5A were changed from to Epileptic encephalopathy, early infantile, 49, 617281
Early onset or syndromic epilepsy v0.1071 DDX3X Rebecca Foulger Marked gene: DDX3X as ready
Early onset or syndromic epilepsy v0.1071 DDX3X Rebecca Foulger Gene: ddx3x has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1071 DDX3X Rebecca Foulger Added comment: Comment on mode of inheritance: OMIM and Gene2Phenotype list MOI as both XLR and XLD.
Early onset or syndromic epilepsy v0.1071 DDX3X Rebecca Foulger Mode of inheritance for gene: DDX3X was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early onset or syndromic epilepsy v0.1070 DDX3X Rebecca Foulger Classified gene: DDX3X as Green List (high evidence)
Early onset or syndromic epilepsy v0.1070 DDX3X Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green: Confirmed DD-G2P for X-linked intellectual disability. MIM:300958 disease includes seizures in some patients. 6 females in PMID:26235985 with 6 different DDX3X variants showed seizures (16%). Therefore sufficient cases for diagnostic rating.
Early onset or syndromic epilepsy v0.1070 DDX3X Rebecca Foulger Gene: ddx3x has been classified as Green List (High Evidence).
Hereditary spastic paraplegia v1.71 ERLIN1 Alistair Pagnamenta gene: ERLIN1 was added
gene: ERLIN1 was added to Hereditary spastic paraplegia. Sources: Other
Mode of inheritance for gene: ERLIN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERLIN1 were set to PMID: 24482476
Phenotypes for gene: ERLIN1 were set to Hereditary spastic paraplegia
Penetrance for gene: ERLIN1 were set to unknown
Review for gene: ERLIN1 was set to GREEN
Added comment: Sources: Other
Early onset or syndromic epilepsy v0.1069 DDX3X Rebecca Foulger Mode of inheritance for gene: DDX3X was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early onset or syndromic epilepsy v0.1068 DDX3X Rebecca Foulger commented on gene: DDX3X
Early onset or syndromic epilepsy v0.1068 DDX3X Rebecca Foulger Phenotypes for gene: DDX3X were changed from to Mental retardation, X-linked 102, 300958
Early onset or syndromic epilepsy v0.1067 PLAA Eleanor Williams Marked gene: PLAA as ready
Early onset or syndromic epilepsy v0.1067 PLAA Eleanor Williams Added comment: Comment when marking as ready: Sufficient cases for disease association, >3 cases with seizures
Early onset or syndromic epilepsy v0.1067 PLAA Eleanor Williams Gene: plaa has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1067 PLAA Eleanor Williams Phenotypes for gene: PLAA were changed from to Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies 617527; Lethal Infantile Epileptic Encephalopathy
Early onset or syndromic epilepsy v0.1066 PLAA Eleanor Williams Publications for gene: PLAA were set to
Early onset or syndromic epilepsy v0.1065 DBT Rebecca Foulger Phenotypes for gene: DBT were changed from to Maple syrup urine disease, type II, 248600
Early onset or syndromic epilepsy v0.1064 PLAA Eleanor Williams Mode of inheritance for gene: PLAA was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1063 PLAA Eleanor Williams Classified gene: PLAA as Green List (high evidence)
Early onset or syndromic epilepsy v0.1063 PLAA Eleanor Williams Added comment: Comment on list classification: 3 variants found in 5 families (but two families likely to have common ancestral haplotype). Seizures reported in all families.
Early onset or syndromic epilepsy v0.1063 PLAA Eleanor Williams Gene: plaa has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1062 HEXA Ivone Leong commented on gene: HEXA: Tay-Sachs disease is rare in the general population but has increased frequency in Ashkenazi Jews. Many of the papers do not specify whether patients have seizures/epilpsy and many report on the patient's phenotype as classic infantile (seizures can be a symptom), juvenile or adult late-onset (seizures can be a symptom), which may or may not necessarily mean patients have seizures. I have only included studies that mention seizures/epilepsy specifically.
Three studies have reported 3 patients with different variants in HEXA gene who have seizures (PMID: 30006889, 21937992, 7551830). PMID: 14972682 describe a mouse model of HEXA which also exhibited seizure/epilpsy phenotype.
Early onset or syndromic epilepsy v0.1062 PLAA Eleanor Williams commented on gene: PLAA
Early onset or syndromic epilepsy v0.1062 DBT Rebecca Foulger Mode of inheritance for gene: DBT was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1061 HEXA Ivone Leong Publications for gene: HEXA were set to
Renal tubulopathies v1.13 AVPR2 Ellen McDonagh Classified gene: AVPR2 as Green List (high evidence)
Renal tubulopathies v1.13 AVPR2 Ellen McDonagh Added comment: Comment on list classification: Promoted to Green.
Renal tubulopathies v1.13 AVPR2 Ellen McDonagh Gene: avpr2 has been classified as Green List (High Evidence).
Renal tubulopathies v1.12 AVPR2 Ellen McDonagh gene: AVPR2 was added
gene: AVPR2 was added to Renal tubulopathies. Sources: Other
treatable tags were added to gene: AVPR2.
Mode of inheritance for gene: AVPR2 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: AVPR2 were set to 18726898; 27565746; 27117808; 26974133; 26828532
Phenotypes for gene: AVPR2 were set to Diabetes insipidus, nephrogenic, 304800; Nephrogenic Diabetes Insipidus; Diabetes Insipidus, Nephrogenic, X-Linked; nephrogenic diabetes insipidus (commonest cause, affected females also reported often with a milder and later presentation)
Added comment: Added this gene from the Monogenic nephrogenic diabetes insipidus (Version 1.8, code 18) gene panel, after request from the Genomics England Clinical Team. There are >3 unrelated cases/families reported. PMID: 9329382 indicates that heterozygous females may be affected, depending on X-linked skewing. The 'treatable' tag was added due to information available on Orphanet regarding Nephrogenic diabetes insipidus: "Patients should receive a low salt diet with limited potassium and protein intake and take thiazide diuretics in combination with indomethacin. This treatment has changed the life of affected patients, especially infants." summary reviewed by : Dr Patrick NIAUDET - Last update: February 2007 (http://www.orpha.net).
Sources: Other
Renal tubulopathies v1.11 AQP2 Ellen McDonagh Classified gene: AQP2 as Green List (high evidence)
Renal tubulopathies v1.11 AQP2 Ellen McDonagh Added comment: Comment on list classification: Promoted to Green.
Renal tubulopathies v1.11 AQP2 Ellen McDonagh Gene: aqp2 has been classified as Green List (High Evidence).
Renal tubulopathies v1.10 AQP2 Ellen McDonagh gene: AQP2 was added
gene: AQP2 was added to Renal tubulopathies. Sources: Other
treatable tags were added to gene: AQP2.
Mode of inheritance for gene: AQP2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: AQP2 were set to 8140421; 7524315; 9048343; 9649557; 9302264; 9745427; 11929850; 12050236; 15509592
Phenotypes for gene: AQP2 were set to Diabetes insipidus, nephrogenic, 125800
Added comment: Added this gene from the Monogenic nephrogenic diabetes insipidus (Version 1.8, code 18) gene panel, after request from the Genomics England Clinical Team. There are >3 unrelated cases/families reported (see publications). Majority of variants reported are missense. Added the 'treatable' tag due to information available on Orphanet regarding Nephrogenic diabetes insipidus: "Patients should receive a low salt diet with limited potassium and protein intake and take thiazide diuretics in combination with indomethacin. This treatment has changed the life of affected patients, especially infants." summary reviewed by : Dr Patrick NIAUDET - Last update: February 2007 (http://www.orpha.net).
Sources: Other
Intellectual disability v2.555 GABRB2 Louise Daugherty commented on gene: GABRB2: New gene added by external expert and reviewed by curation team. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association and to rate this gene as Green
Intellectual disability v2.555 GABRB2 Louise Daugherty Deleted their comment
Early onset or syndromic epilepsy v0.1060 GABRB2 Louise Daugherty Marked gene: GABRB2 as ready
Early onset or syndromic epilepsy v0.1060 GABRB2 Louise Daugherty Gene: gabrb2 has been classified as Green List (High Evidence).
Intellectual disability v2.555 GABRB2 Louise Daugherty Classified gene: GABRB2 as Green List (high evidence)
Intellectual disability v2.555 GABRB2 Louise Daugherty Added comment: Comment on list classification: New gene added by external expert and reviewed by curation team, enough evidence to support gene-disease association and relevance to this panel to rate this gene Green.
Intellectual disability v2.555 GABRB2 Louise Daugherty Gene: gabrb2 has been classified as Green List (High Evidence).
Intellectual disability v2.554 PHACTR1 Konstantinos Varvagiannis reviewed gene: PHACTR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30256902, 23033978, 28135719; Phenotypes: Global developmental delay, Intellectual disability, Seizures; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v0.1060 PHACTR1 Konstantinos Varvagiannis gene: PHACTR1 was added
gene: PHACTR1 was added to Genetic epilepsy syndromes. Sources: Literature,Expert Review
Mode of inheritance for gene: PHACTR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PHACTR1 were set to 30256902; 23033978; 28135719
Phenotypes for gene: PHACTR1 were set to Global developmental delay; Intellectual disability; Seizures
Penetrance for gene: PHACTR1 were set to unknown
Review for gene: PHACTR1 was set to GREEN
Added comment: PMID: 30256902 (Hamada et al., 2018) reports on the phenotype of 2 unrelated individuals with de novo missense variants in PHACTR1. Both had a diagnosis of West syndrome (infantile spasms and intellectual disability).

As the authors note, 3 individuals with missense variants in this gene (in 2 of whom as a de novo occurrence) were previously identified :
- In PMID: 23033978 (de Ligt et al., 2012) one patient with ID and epilepsy and a de novo missense variant.
- In PMID: 28135719 (DDD study in 2017) one individual with developmental disorder and a further de novo missense SNV.
- PMID: 27457812 (Riazuddin et al., 2017) is an exome sequencing study for intellectual disability. (NB. In the supplement of this study, the consanguineous parents of the affected individuals appear to be heterozygous for this variant but the affected children non-carriers).

Extensive functional studies for the 2 novel as the 2 previously reported variants (from PMIDs: 23033978, 28135719) support a dominant negative effect for all 4 variants.

One of these variants (reported by de Ligt al.) for which pathogenicity is suggested has however been reported 4 times in gnomAD. The authors discuss the possibility of reduced penetrance and/or other phenotypes in the individuals from gnomAD.

Although all the variants studied appear to have a dominant negative effect, Phactr1-knockdown neurons seem to display aberrant migration and morphological phenotype. As a result, the eventual effect of haploinsufficiency probably needs to be further clarified. (Still PHACTR1 has a pLI score of 0.66 in ExAC).

At least 3 individuals appeared to have epilepsy (as this information is not available for the DDD participant).

As a result, this gene can be considered for inclusion in this panel as green (or amber).
Sources: Literature, Expert Review
Early onset or syndromic epilepsy v0.1060 HCFC1 Ivone Leong Publications for gene: HCFC1 were set to 24011988; 23000143; 25740848
Early onset or syndromic epilepsy v0.1059 PIK3CA Eleanor Williams Marked gene: PIK3CA as ready
Early onset or syndromic epilepsy v0.1059 PIK3CA Eleanor Williams Added comment: Comment when marking as ready: Sufficient cases
Early onset or syndromic epilepsy v0.1059 PIK3CA Eleanor Williams Gene: pik3ca has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1059 PIK3CA Eleanor Williams Classified gene: PIK3CA as Green List (high evidence)
Early onset or syndromic epilepsy v0.1059 PIK3CA Eleanor Williams Added comment: Comment on list classification: > 3 cases of variants in this gene associated with phenotype, and with seizures
Early onset or syndromic epilepsy v0.1059 PIK3CA Eleanor Williams Gene: pik3ca has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1058 PIK3CA Eleanor Williams Phenotypes for gene: PIK3CA were changed from to Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic 602501
Early onset or syndromic epilepsy v0.1057 PIK3CA Eleanor Williams Publications for gene: PIK3CA were set to
Early onset or syndromic epilepsy v0.1056 PIK3CA Eleanor Williams Added comment: Comment on mode of pathogenicity: Gain of function
Early onset or syndromic epilepsy v0.1056 PIK3CA Eleanor Williams Mode of pathogenicity for gene: PIK3CA was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v2.554 GABRB2 Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Intellectual disability panel
Intellectual disability v2.554 GABRB2 Louise Daugherty Phenotypes for gene: GABRB2 were changed from intellectual disability to Epileptic encephalopathy, infantile or early childhood, 2, 617829; intellectual disability
Early onset or syndromic epilepsy v0.1055 GABRB2 Louise Daugherty Marked gene: GABRB2 as ready
Early onset or syndromic epilepsy v0.1055 GABRB2 Louise Daugherty Gene: gabrb2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1055 GABRB2 Louise Daugherty Classified gene: GABRB2 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1055 GABRB2 Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association
Early onset or syndromic epilepsy v0.1055 GABRB2 Louise Daugherty Gene: gabrb2 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1054 GABRB2 Louise Daugherty Mode of inheritance for gene: GABRB2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v0.1053 GABRB2 Louise Daugherty Added comment: Comment on publications: Added publications suggested from external expert review to support upgrading of the gene to Green. Hamdan et al. (2017) PMID 29100083 reported 3 unrelated cases with de novo missense variants in GABRB2 who had developmental and epileptic encephalopathy. Srivastava et al. (2014) PMID 25124326 . Ishii et al. (2017) PMID: 27789573 describes a 12-year old girl with intellectual disability and epilepsy due to another de novo missense variant in GABRB2 epileptic seizures. Ishii et al. (2017) PMID 27789573 describes a patient with early myoclonic encephalopathy and severe psycomotor delay, due to a de novo heterozygous missense mutation in GABRB2.
Early onset or syndromic epilepsy v0.1053 GABRB2 Louise Daugherty Publications for gene: GABRB2 were set to
Early onset or syndromic epilepsy v0.1052 GABRB2 Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Early onset or syndromic epilepsy v0.1052 GABRB2 Louise Daugherty Phenotypes for gene: GABRB2 were changed from to Epileptic encephalopathy, infantile or early childhood, 2, 617829
Thoracic aortic aneurysm or dissection v1.77 ABL1 Chris Buxton gene: ABL1 was added
gene: ABL1 was added to Thoracic aortic aneurysm or dissection. Sources: Literature
Mode of inheritance for gene: ABL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ABL1 were set to 28288113
Phenotypes for gene: ABL1 were set to Congenital finger flexion contractures (HP:0005879); Congenital septal defect (HP:0004760); Generalized joint laxity (HP:0002761); Ascending aortic dilation (HP:0004970); Scoliosis (HP:0002650); Failure to thrive in infancy (HP:0001531); Hypospadias (HP:0000047); Pectus excavatum (HP:0000767)
Penetrance for gene: ABL1 were set to unknown
Mode of pathogenicity for gene: ABL1 was set to Other
Review for gene: ABL1 was set to RED
Added comment: Gain of function variants in this gene are described by Wang (2017, PMID 28288113) as a ddx for TGFB overexpression pathway disorders, eg Loeys Dietz, Shprintzen Goldberg, Marfan syndrome.

Wang X et al., Germline mutations in ABL1 cause an autosomal dominant syndrome characterized by congenital heart defects and skeletal malformations. Nat Genet. 2017 Apr;49(4):613-617.
Sources: Literature
Early onset or syndromic epilepsy v0.1051 GALC Louise Daugherty Marked gene: GALC as ready
Early onset or syndromic epilepsy v0.1051 GALC Louise Daugherty Gene: galc has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1051 GALC Louise Daugherty Classified gene: GALC as Green List (high evidence)
Early onset or syndromic epilepsy v0.1051 GALC Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association
Early onset or syndromic epilepsy v0.1051 GALC Louise Daugherty Gene: galc has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1050 PTS Sarah Leigh Classified gene: PTS as Red List (low evidence)
Early onset or syndromic epilepsy v0.1050 PTS Sarah Leigh Added comment: Comment on list classification: Although the phenotype in OMIM and Gen2Phen gene. However, unable to find reports of seizures in variant carriers.
Early onset or syndromic epilepsy v0.1050 PTS Sarah Leigh Gene: pts has been classified as Red List (Low Evidence).
Early onset or syndromic epilepsy v0.1049 GALC Louise Daugherty Added comment: Comment on publications: Added publications to support upgrading of the gene to Green
Early onset or syndromic epilepsy v0.1049 GALC Louise Daugherty Publications for gene: GALC were set to
Early onset or syndromic epilepsy v0.1048 GALC Louise Daugherty Added comment: Comment on mode of inheritance: changed MOI from external clinical review and publications
Early onset or syndromic epilepsy v0.1048 GALC Louise Daugherty Mode of inheritance for gene: GALC was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1047 GALC Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Early onset or syndromic epilepsy v0.1047 GALC Louise Daugherty Phenotypes for gene: GALC were changed from to Krabbe disease, 245200; seizures; CALC deficiency; Galactosylceramide beta-galactosidase deficiency
Early onset or syndromic epilepsy v0.1046 GAMT Louise Daugherty Marked gene: GAMT as ready
Early onset or syndromic epilepsy v0.1046 GAMT Louise Daugherty Gene: gamt has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1046 PIK3CA Eleanor Williams Added comment: Comment on mode of inheritance: Note somatic mosiacism
Early onset or syndromic epilepsy v0.1046 PIK3CA Eleanor Williams Mode of inheritance for gene: PIK3CA was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v0.1045 PIK3CA Eleanor Williams Tag mosaicism tag was added to gene: PIK3CA.
Tag somatic tag was added to gene: PIK3CA.
Early onset or syndromic epilepsy v0.1045 PIK3CA Eleanor Williams commented on gene: PIK3CA
Early onset or syndromic epilepsy v0.1045 KCNQ5 Ivone Leong Classified gene: KCNQ5 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1045 KCNQ5 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. Have checked with Eleanor Williams (Genomic England) that two probands with different variants who have the same ethnic background is accepted as two separate pieces of evidence.
Early onset or syndromic epilepsy v0.1045 KCNQ5 Ivone Leong Gene: kcnq5 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1044 GAMT Louise Daugherty Added comment: Comment on phenotypes: added synonyms
Early onset or syndromic epilepsy v0.1044 GAMT Louise Daugherty Phenotypes for gene: GAMT were changed from Cerebral creatine deficiency syndrome 2, 612736; Seizures; Deficiency of guanidinoacetate methyltransferase to Cerebral creatine deficiency syndrome 2, 612736; Seizures; Deficiency of guanidinoacetate methyltransferase; GAMT deficiency
Early onset or syndromic epilepsy v0.1043 GAMT Louise Daugherty Publications for gene: GAMT were set to 15651030; 17101918; 15108290; 19027335
Early onset or syndromic epilepsy v0.1042 GAMT Louise Daugherty Classified gene: GAMT as Green List (high evidence)
Early onset or syndromic epilepsy v0.1042 GAMT Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association
Early onset or syndromic epilepsy v0.1042 GAMT Louise Daugherty Gene: gamt has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1041 GAMT Louise Daugherty Added comment: Comment on publications: Added publications s to support upgrading of the gene to Green
Early onset or syndromic epilepsy v0.1041 GAMT Louise Daugherty Publications for gene: GAMT were set to
Early onset or syndromic epilepsy v0.1040 MAP2K1 Ivone Leong Publications for gene: MAP2K1 were set to
Early onset or syndromic epilepsy v0.1039 GAMT Louise Daugherty Phenotypes for gene: GAMT were changed from Cerebral creatine deficiency syndrome 2, 612736; Seizures to Cerebral creatine deficiency syndrome 2, 612736; Seizures; Deficiency of guanidinoacetate methyltransferase
Early onset or syndromic epilepsy v0.1038 GAMT Louise Daugherty Added comment: Comment on mode of inheritance: Added MOI from external clinical review and publications
Early onset or syndromic epilepsy v0.1038 GAMT Louise Daugherty Mode of inheritance for gene: GAMT was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1037 GAMT Louise Daugherty Added comment: Comment on phenotypes: Not added the expert review phenotype Krabbe disease as it related to the previously reviewed gene GALC. Cerebral creatine deficiency syndrome 2, 612736 is the disorder associated to variants of this gene, and is relevant for inclusion on the Genetic Epilepsy Syndromes panel
Early onset or syndromic epilepsy v0.1037 GAMT Louise Daugherty Phenotypes for gene: GAMT were changed from to Cerebral creatine deficiency syndrome 2, 612736; Seizures
Early onset or syndromic epilepsy v0.1036 MAP2K1 Ivone Leong Mode of inheritance for gene: MAP2K1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v1.55 TBC1D24 Louise Daugherty Publications for gene: TBC1D24 were set to 10574461; 10741954; 20727515; 20797691; 21087195; 22211675; 23343562; 23526554; 24291220; 24387994; 24729539; 24729547
Monogenic hearing loss v1.54 TBC1D24 Louise Daugherty Classified gene: TBC1D24 as Green List (high evidence)
Monogenic hearing loss v1.54 TBC1D24 Louise Daugherty Added comment: Comment on list classification: Changed from Red to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association
Monogenic hearing loss v1.54 TBC1D24 Louise Daugherty Gene: tbc1d24 has been classified as Green List (High Evidence).
Monogenic hearing loss v1.53 TBC1D24 Louise Daugherty Mode of inheritance for gene: TBC1D24 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v1.52 TBC1D24 Louise Daugherty Added comment: Comment on publications: Added publications suggested from external expert review to support upgrading of the gene to Green
Monogenic hearing loss v1.52 TBC1D24 Louise Daugherty Publications for gene: TBC1D24 were set to
Monogenic hearing loss v1.51 TBC1D24 Louise Daugherty Phenotypes for gene: TBC1D24 were changed from Deafness , autosomal recessive 86, 614617; Deafness, autosomal dominant 65, 616044; DOORS syndrome, 220500; deafness, onychodystrophy, osteodystrophy, and mental retardation to Deafness, autosomal recessive 86, 614617; Deafness, autosomal dominant 65, 616044; DOORS syndrome, 220500; deafness, onychodystrophy, osteodystrophy, and mental retardation
Monogenic hearing loss v1.50 TBC1D24 Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes that indicate relevance to inclusion on the Hearing loss panel from OMIM. removed: Myoclonic epilepsy, infantile, familial, 605021;Myoclonicepilepsy,infantile,familial,605021Epilepticencephalopathy,earlyinfantile,16,615338
Monogenic hearing loss v1.50 TBC1D24 Louise Daugherty Phenotypes for gene: TBC1D24 were changed from Myoclonic epilepsy, infantile, familial, 605021; Myoclonicepilepsy,infantile,familial,605021Epilepticencephalopathy,earlyinfantile,16,615338 to Deafness , autosomal recessive 86, 614617; Deafness, autosomal dominant 65, 616044; DOORS syndrome, 220500; deafness, onychodystrophy, osteodystrophy, and mental retardation
Early onset or syndromic epilepsy v0.1035 MAP2K1 Ivone Leong Phenotypes for gene: MAP2K1 were changed from to Cardiofaciocutaneous syndrome 3, 615279
Early onset or syndromic epilepsy v0.1034 PIGW Eleanor Williams Marked gene: PIGW as ready
Early onset or syndromic epilepsy v0.1034 PIGW Eleanor Williams Added comment: Comment when marking as ready: Sufficient cases to make green
Early onset or syndromic epilepsy v0.1034 PIGW Eleanor Williams Gene: pigw has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1034 PIGW Eleanor Williams Phenotypes for gene: PIGW were changed from to Glycosylphosphatidylinositol biosynthesis defect 11, 616025; HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME 5
Early onset or syndromic epilepsy v0.1033 PIGW Eleanor Williams Publications for gene: PIGW were set to 24367057; 27626616; 30078644
Early onset or syndromic epilepsy v0.1032 PIGW Eleanor Williams Publications for gene: PIGW were set to
Early onset or syndromic epilepsy v0.1031 LIAS Ivone Leong Marked gene: LIAS as ready
Early onset or syndromic epilepsy v0.1031 LIAS Ivone Leong Gene: lias has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1031 LIAS Ivone Leong Classified gene: LIAS as Green List (high evidence)
Early onset or syndromic epilepsy v0.1031 LIAS Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. Phenotype confirmed by both OMIM and Gene2Phenotype.

There are only 4 reported cases of this disease in 3 papers (PMID: 24334290, 22152680, 26108146). Of the three cases, all patients (2 of Turkish descent and 1 of Somali descent) have different variants in the LIAS gene and they all have seizures (PMID: 24334290, 22152680).
Early onset or syndromic epilepsy v0.1031 LIAS Ivone Leong Gene: lias has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1030 PIGW Eleanor Williams Mode of inheritance for gene: PIGW was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1029 PIGW Eleanor Williams Classified gene: PIGW as Green List (high evidence)
Early onset or syndromic epilepsy v0.1029 PIGW Eleanor Williams Added comment: Comment on list classification: 3 cases/families reported, all with seizures
Early onset or syndromic epilepsy v0.1029 PIGW Eleanor Williams Gene: pigw has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1028 PIGW Eleanor Williams commented on gene: PIGW
Early onset or syndromic epilepsy v0.1028 PIGO Eleanor Williams Marked gene: PIGO as ready
Early onset or syndromic epilepsy v0.1028 PIGO Eleanor Williams Added comment: Comment when marking as ready: Sufficient cases with compound heterozygous mutations in PIGO and 3 cases with seizures.
Early onset or syndromic epilepsy v0.1028 PIGO Eleanor Williams Gene: pigo has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1028 PIGO Eleanor Williams Publications for gene: PIGO were set to 22683086; 24049131; 24417746; 28900819
Retinal disorders v1.88 SCAPER Louise Daugherty Added comment: Comment on phenotypes: added phenotype and MIM from OMIM : Tatour et al. (2017) PMID: 28794130 describes 4 patients from 3 unrelated families with intellectual disability disorder and retinitis pigmentosa and identified homozygosity or compound heterozygosity for mutations in the SCAPER gene. Noting that the retinal phenotype associated with null SCAPER mutations is not congenital but presents around the second decade of life, the authors suggested that in the retina, SCAPER does not play a developmental role, but rather is important for photoreceptor function and/or maintenance.
Retinal disorders v1.88 SCAPER Louise Daugherty Phenotypes for gene: SCAPER were changed from More than one phenotype including syndromic cases for syndromic forms of Inherited retinal disease or albinism to More than one phenotype including syndromic cases for syndromic forms of Inherited retinal disease or albinism; Intellectual developmental disorder and retinitis pigmentosa, 618195
Intellectual disability v2.553 SCAPER Louise Daugherty Added comment: Comment on publications: Added publications to support upgrading of the gene to Green
Intellectual disability v2.553 SCAPER Louise Daugherty Publications for gene: SCAPER were set to 21937992
Intellectual disability v2.552 SCAPER Louise Daugherty edited their review of gene: SCAPER: Changed rating: AMBER
Intellectual disability v2.552 SCAPER Louise Daugherty Added comment: Comment on phenotypes: added phenotype and MIM from OMIM : Tatour et al. (2017) PMID: 28794130 describes 4 patients from 3 unrelated families with intellectual disability disorder and retinitis pigmentosa and identified homozygosity or compound heterozygosity for mutations in the SCAPER gene. Noting that the retinal phenotype associated with null SCAPER mutations is not congenital but presents around the second decade of life, the authors suggested that in the retina, SCAPER does not play a developmental role, but rather is important for photoreceptor function and/or maintenance.
Intellectual disability v2.552 SCAPER Louise Daugherty Phenotypes for gene: SCAPER were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION to AUTOSOMAL RECESSIVE MENTAL RETARDATION; Intellectual developmental disorder and retinitis pigmentosa, 618195
Early onset or syndromic epilepsy v0.1027 PIGO Eleanor Williams Phenotypes for gene: PIGO were changed from to Hyperphosphatasia with mental retardation syndrome 2, 614749
Early onset or syndromic epilepsy v0.1026 PIGO Eleanor Williams Added comment: Comment on publications: Further cases reported in PMIDs: 28900819 and 28337824
Early onset or syndromic epilepsy v0.1026 PIGO Eleanor Williams Publications for gene: PIGO were set to
Early onset or syndromic epilepsy v0.1025 PIGO Eleanor Williams Mode of inheritance for gene: PIGO was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1024 PIGO Eleanor Williams Classified gene: PIGO as Green List (high evidence)
Early onset or syndromic epilepsy v0.1024 PIGO Eleanor Williams Added comment: Comment on list classification: Sufficient cases with compound heterogzyous mutations in PIGO and 3 cases with seizures.
Early onset or syndromic epilepsy v0.1024 PIGO Eleanor Williams Gene: pigo has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1023 PIGO Eleanor Williams commented on gene: PIGO
Early onset or syndromic epilepsy v0.1023 LARGE1 Ivone Leong Marked gene: LARGE1 as ready
Early onset or syndromic epilepsy v0.1023 LARGE1 Ivone Leong Gene: large1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1023 LARGE1 Ivone Leong Classified gene: LARGE1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v0.1023 LARGE1 Ivone Leong Added comment: Comment on list classification: Phenotype confirmed by both OMIM and Gene2Phenotype. However, there is only one reported case of a patient with mutations in LARGE1 who also have seizures (PMID: 24709677). Therefore not enough evidence to promote to green status.
Early onset or syndromic epilepsy v0.1023 LARGE1 Ivone Leong Gene: large1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1022 LARGE1 Ivone Leong Publications for gene: LARGE1 were set to
Intellectual disability v2.551 NUDT2 Konstantinos Varvagiannis gene: NUDT2 was added
gene: NUDT2 was added to Intellectual disability. Sources: Literature,Expert Review
Mode of inheritance for gene: NUDT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDT2 were set to 27431290; 30059600
Phenotypes for gene: NUDT2 were set to Muscular hypotonia; Global developmental delay; Intellectual disability
Penetrance for gene: NUDT2 were set to Complete
Review for gene: NUDT2 was set to AMBER
Added comment: PMID: 27431290 reports briefly on 2 sibs from a consanguineous Saudi family, as part of a cohort of 337 patients investigated for intellectual disability. Both were homozygous for a nonsense NUDT2 mutation [NM_001161.4:c.34C>T or p.Arg12Ter / rs148119952]. The common features included hypotonia, global developmental delay (first words at 2.5 years, sitting at 2-2.5 years,walking achieved by 4 years - valid for both sibs) and intellectual disability. No other candidate variants were found in the exome.

PMID: 30059600 is a further report on 5 individuals from 3 consanguineous families from Saudi Arabia. All presented with low birth weight and height, poor suck, hypotonia, motor and language delay and borderline intelligence. All patients were homozygous for the same nonsense variant (Arg12Ter) which seems to be a founder mutation in Saudi Arabia.

As truncating NUDT2 variants have a combined allele frequency of 0.02% in gnomAD (no homozygotes in the database) the authors comment that most of the other LoF variants observed are in the second - and last - exon of the gene (thus probably escaping NMD) and downstream of its catalytic domain.

As a result this gene can be considered for inclusion in the ID panel probably as amber (single founder mutation - the degree of intellectual disability appears to be more severe in the first report but borderline in the subsequent) or green.
Sources: Literature, Expert Review
Early onset or syndromic epilepsy v0.1021 PHGDH Eleanor Williams Marked gene: PHGDH as ready
Early onset or syndromic epilepsy v0.1021 PHGDH Eleanor Williams Added comment: Comment when marking as ready: Sufficient cases reported with seizures.
Early onset or syndromic epilepsy v0.1021 PHGDH Eleanor Williams Gene: phgdh has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1021 PHGDH Eleanor Williams Phenotypes for gene: PHGDH were changed from to Phosphoglycerate dehydrogenase deficiency 601815
Early onset or syndromic epilepsy v0.1020 PHGDH Eleanor Williams Publications for gene: PHGDH were set to
Early onset or syndromic epilepsy v0.1019 PHGDH Eleanor Williams Mode of inheritance for gene: PHGDH was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1018 PHGDH Eleanor Williams Classified gene: PHGDH as Green List (high evidence)
Early onset or syndromic epilepsy v0.1018 PHGDH Eleanor Williams Added comment: Comment on list classification: More than 3 variants associated with the disorder. Patients from 7 families present with seizures.
Early onset or syndromic epilepsy v0.1018 PHGDH Eleanor Williams Gene: phgdh has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1017 PHGDH Eleanor Williams commented on gene: PHGDH
Early onset or syndromic epilepsy v0.1017 PDHX Eleanor Williams Marked gene: PDHX as ready
Early onset or syndromic epilepsy v0.1017 PDHX Eleanor Williams Added comment: Comment when marking as ready: Sufficient variants to associate with disorder. At least 3 cases where seizures are part of the phenotype.
Early onset or syndromic epilepsy v0.1017 PDHX Eleanor Williams Gene: pdhx has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1017 PDHX Eleanor Williams Phenotypes for gene: PDHX were changed from to Lacticacidemia due to PDX1 deficiency 245349
Early onset or syndromic epilepsy v0.1016 PDHX Eleanor Williams Publications for gene: PDHX were set to
Early onset or syndromic epilepsy v0.1015 PDHX Eleanor Williams Mode of inheritance for gene: PDHX was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1014 PDHX Eleanor Williams Classified gene: PDHX as Green List (high evidence)
Early onset or syndromic epilepsy v0.1014 PDHX Eleanor Williams Added comment: Comment on list classification: Numerous variants in this gene associated with Lacticacidemia are reported. 3 cases where seizures are part of the phenotype.
Early onset or syndromic epilepsy v0.1014 PDHX Eleanor Williams Gene: pdhx has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1013 PDHX Eleanor Williams commented on gene: PDHX
Pain syndromes v1.3 Ellen McDonagh List of related panels changed from neuropathic pain;Pain channelopathies to neuropathic pain; Pain channelopathies
Early onset or syndromic epilepsy v0.1013 GBA Louise Daugherty Marked gene: GBA as ready
Early onset or syndromic epilepsy v0.1013 GBA Louise Daugherty Gene: gba has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1013 PDHA1 Eleanor Williams Marked gene: PDHA1 as ready
Early onset or syndromic epilepsy v0.1013 PDHA1 Eleanor Williams Added comment: Comment when marking as ready: Sufficient cases.
Early onset or syndromic epilepsy v0.1013 PDHA1 Eleanor Williams Gene: pdha1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1013 PDHA1 Eleanor Williams Classified gene: PDHA1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.1013 PDHA1 Eleanor Williams Added comment: Comment on list classification: > 3 cases of patients with variants in this gene with Pyruvate dehydrogenase E1-alpha deficiency and with seizures as part of the phenotype.
Early onset or syndromic epilepsy v0.1013 PDHA1 Eleanor Williams Gene: pdha1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1012 GBA Louise Daugherty Classified gene: GBA as Green List (high evidence)
Early onset or syndromic epilepsy v0.1012 GBA Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association
Early onset or syndromic epilepsy v0.1012 GBA Louise Daugherty Gene: gba has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.1011 PDHA1 Eleanor Williams Added comment: Comment on mode of inheritance: Heterozygous mutations seen in females showing phenotype.
Early onset or syndromic epilepsy v0.1011 PDHA1 Eleanor Williams Mode of inheritance for gene: PDHA1 was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Early onset or syndromic epilepsy v0.1010 PDHA1 Eleanor Williams Added comment: Comment on phenotypes: Siezures are listed as part of the phenotype for X-LINKED LEIGH SYNDROME, PYRUVATE DEHYDROGENASE E1-ALPHA DEFICIENCY IN FEMALES and INTELLECTUAL DISABILTIY in Gene2Phenotype
Early onset or syndromic epilepsy v0.1010 PDHA1 Eleanor Williams Phenotypes for gene: PDHA1 were changed from to Pyruvate dehydrogenase E1-alpha deficiency 312170; X-LINKED LEIGH SYNDROME; PYRUVATE DEHYDROGENASE E1-ALPHA DEFICIENCY IN FEMALES; INTELLECTUAL DISABILTIY
Early onset or syndromic epilepsy v0.1009 PDHA1 Eleanor Williams Publications for gene: PDHA1 were set to
Early onset or syndromic epilepsy v0.1008 PDHA1 Eleanor Williams commented on gene: PDHA1
Early onset or syndromic epilepsy v0.1008 GBA Louise Daugherty Publications for gene: GBA were set to 8929950; 15214004; 12838552; 8829654; 8118460
Early onset or syndromic epilepsy v0.1007 LIAS Ivone Leong Mode of inheritance for gene: LIAS was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1006 LIAS Ivone Leong Phenotypes for gene: LIAS were changed from to Hyperglycinemia, lactic acidosis, and seizures, 614462
Early onset or syndromic epilepsy v0.1005 LARGE1 Ivone Leong Mode of inheritance for gene: LARGE1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.1004 LARGE1 Ivone Leong Phenotypes for gene: LARGE1 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6, 613154; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 6, 608840
Early onset or syndromic epilepsy v0.1003 KRAS Ivone Leong Classified gene: KRAS as Amber List (moderate evidence)
Early onset or syndromic epilepsy v0.1003 KRAS Ivone Leong Added comment: Comment on list classification: Cardiofaciocutaneous syndrome 2 was confirmed on both OMIM and Gene2Phenotype. One report (PMID: 16474405) found one proband with a missense variant in the KRAS gene that had seizures, and another study (PMID: 21871821) found 2 unrelated Japanese probands with missense mutations who have seizures. There is not enough evidence to promote the gene.
Early onset or syndromic epilepsy v0.1003 KRAS Ivone Leong Gene: kras has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.1002 GBA Louise Daugherty Added comment: Comment on publications: Added publications to support upgrading of the gene to Green
Early onset or syndromic epilepsy v0.1002 GBA Louise Daugherty Publications for gene: GBA were set to
Early onset or syndromic epilepsy v0.1001 KRAS Ivone Leong Publications for gene: KRAS were set to
Early onset or syndromic epilepsy v0.1000 KRAS Ivone Leong Added comment: Comment on mode of pathogenicity: Variants cause gain-of-function effects (PMID: 21871821, 23059812).
Early onset or syndromic epilepsy v0.1000 KRAS Ivone Leong Mode of pathogenicity for gene: KRAS was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Early onset or syndromic epilepsy v0.999 GBA Louise Daugherty Added comment: Comment on mode of inheritance: Added MOI from external clinical review and publications
Early onset or syndromic epilepsy v0.999 GBA Louise Daugherty Mode of inheritance for gene: GBA was changed from to BIALLELIC, autosomal or pseudoautosomal
Thoracic aortic aneurysm or dissection v1.77 Ellen McDonagh List of related panels changed from Familial retinal arteriolar tortuosity;FTAAD;Familial Thoracic Aortic Aneurysm Disease to Familial retinal arteriolar tortuosity; FTAAD; Familial Thoracic Aortic Aneurysm Disease
Early onset or syndromic epilepsy v0.998 GBA Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review and reviewed literature that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Early onset or syndromic epilepsy v0.998 GBA Louise Daugherty Phenotypes for gene: GBA were changed from to Gaucher disease, perinatal lethal, 608013; Gaucher disease, type II, 230900; Gaucher disease, type III, 231000; Gaucher disease, type IIIC, 231005; seizures
Early onset or syndromic epilepsy v0.997 GCH1 Louise Daugherty Marked gene: GCH1 as ready
Early onset or syndromic epilepsy v0.997 GCH1 Louise Daugherty Gene: gch1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.997 GCH1 Louise Daugherty Classified gene: GCH1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.997 GCH1 Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association
Early onset or syndromic epilepsy v0.997 GCH1 Louise Daugherty Gene: gch1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.996 GCH1 Louise Daugherty Mode of inheritance for gene: GCH1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.995 GCH1 Louise Daugherty Added comment: Comment on publications: Added publications to support upgrading of the gene to Green
Early onset or syndromic epilepsy v0.995 GCH1 Louise Daugherty Publications for gene: GCH1 were set to
Early onset or syndromic epilepsy v0.994 PCCB Eleanor Williams Phenotypes for gene: PCCB were changed from to Propionicacidemia 606054
Early onset or syndromic epilepsy v0.993 PCCB Eleanor Williams Publications for gene: PCCB were set to
Early onset or syndromic epilepsy v0.992 PCCB Eleanor Williams commented on gene: PCCB
Early onset or syndromic epilepsy v0.992 PCCB Eleanor Williams Mode of inheritance for gene: PCCB was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.991 GCH1 Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Early onset or syndromic epilepsy v0.991 GCH1 Louise Daugherty Phenotypes for gene: GCH1 were changed from to Hyperphenylalaninemia, BH4-deficient, B, 233910; seizures
Early onset or syndromic epilepsy v0.990 PTS Sarah Leigh Classified gene: PTS as Green List (high evidence)
Early onset or syndromic epilepsy v0.990 PTS Sarah Leigh Gene: pts has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.989 PCCB Eleanor Williams commented on gene: PCCB
Early onset or syndromic epilepsy v0.989 PTS Sarah Leigh Phenotypes for gene: PTS were changed from to Hyperphenylalaninemia, BH4-deficient, A, 261640
Early onset or syndromic epilepsy v0.988 PTS Sarah Leigh Publications for gene: PTS were set to
Early onset or syndromic epilepsy v0.987 GFAP Louise Daugherty Marked gene: GFAP as ready
Early onset or syndromic epilepsy v0.987 GFAP Louise Daugherty Gene: gfap has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.987 PTS Sarah Leigh Mode of inheritance for gene: PTS was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.986 GFAP Louise Daugherty Classified gene: GFAP as Green List (high evidence)
Early onset or syndromic epilepsy v0.986 GFAP Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association
Early onset or syndromic epilepsy v0.986 GFAP Louise Daugherty Gene: gfap has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.985 GFAP Louise Daugherty Mode of inheritance for gene: GFAP was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v0.984 GFAP Louise Daugherty Phenotypes for gene: GFAP were changed from to Alexander disease, 203450; seizures
Early onset or syndromic epilepsy v0.983 GFAP Louise Daugherty Added comment: Comment on publications: Added publications suggested from external expert review to support upgrading of the gene to Green. From OMIM PMID: 12034785 Gorospe et al. (2002) reported 12 genetically confirmed cases of Alexander disease. Seven of the 12 had onset in infancy (range 2-18 months), with seizures being the most common presenting sign, followed by failure to thrive and delayed motor development.
Early onset or syndromic epilepsy v0.983 GFAP Louise Daugherty Publications for gene: GFAP were set to
Early onset or syndromic epilepsy v0.982 KRAS Ivone Leong Mode of inheritance for gene: KRAS was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v2.551 GFAP Louise Daugherty Publications for gene: GFAP were set to
Early onset or syndromic epilepsy v0.981 PCCA Eleanor Williams Publications for gene: PCCA were set to 2213454; 25875215; 30014764
Early onset or syndromic epilepsy v0.980 D2HGDH Rebecca Foulger Marked gene: D2HGDH as ready
Early onset or syndromic epilepsy v0.980 D2HGDH Rebecca Foulger Gene: d2hgdh has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.980 D2HGDH Rebecca Foulger Phenotypes for gene: D2HGDH were changed from D-2-hydroxyglutaric aciduria, 600721; generalized tonic-clonic seizures; absence seizures; tonic seizures; tonic-clonic seizures; myoclonic seizures, to D-2-hydroxyglutaric aciduria, 600721; generalized tonic-clonic seizures; absence seizures; tonic seizures; tonic-clonic seizures; myoclonic seizures
Early onset or syndromic epilepsy v0.979 D2HGDH Rebecca Foulger Phenotypes for gene: D2HGDH were changed from D-2-hydroxyglutaric aciduria, 600721 to D-2-hydroxyglutaric aciduria, 600721; generalized tonic-clonic seizures; absence seizures; tonic seizures; tonic-clonic seizures; myoclonic seizures,
Early onset or syndromic epilepsy v0.978 D2HGDH Rebecca Foulger Classified gene: D2HGDH as Green List (high evidence)
Early onset or syndromic epilepsy v0.978 D2HGDH Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green. Green review, and as Zornitza reports, epilepsy is a phenotype of D-2-hydroxyglutaric aciduria. Sufficient unrelated epileptic cases from the literature (2 from PMID:15609246 and 1 from PMID:16037974) to support a diagnostic rating.
Early onset or syndromic epilepsy v0.978 D2HGDH Rebecca Foulger Gene: d2hgdh has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.977 D2HGDH Rebecca Foulger commented on gene: D2HGDH: Struys et al 2005 (PMID:15609246) report two unrelated patients affected with severe D-2-hydroxyglutaric aciduria and disease-causing variants in D2HGDH. Patient one suffered tonic, tonic-clonic, and myoclonic seizures, and was homozygous for missense variant in D2HGDH (c.1331T-->C; p.Val444Ala). Patient 2 presented with generalized tonic-clonic seizures and infantile spasms amongst her symptoms. She was compound heterozygous for a missense mutation (c.440T-->G; p.Ile147Ser) and a splice-site mutation (IVS1-23A-->G) that resulted in a null allele.
Early onset or syndromic epilepsy v0.977 D2HGDH Rebecca Foulger commented on gene: D2HGDH
Early onset or syndromic epilepsy v0.977 PCCA Eleanor Williams Phenotypes for gene: PCCA were changed from to Propionicacidemia 606054
Early onset or syndromic epilepsy v0.976 PCCA Eleanor Williams Publications for gene: PCCA were set to
Early onset or syndromic epilepsy v0.975 PCCA Eleanor Williams Mode of inheritance for gene: PCCA was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.974 PCCA Eleanor Williams commented on gene: PCCA
Early onset or syndromic epilepsy v0.974 GLB1 Louise Daugherty Marked gene: GLB1 as ready
Early onset or syndromic epilepsy v0.974 GLB1 Louise Daugherty Gene: glb1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.974 GLB1 Louise Daugherty Classified gene: GLB1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.974 GLB1 Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association
Early onset or syndromic epilepsy v0.974 GLB1 Louise Daugherty Gene: glb1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.973 GLB1 Louise Daugherty Publications for gene: GLB1 were set to
Early onset or syndromic epilepsy v0.972 UFM1 Konstantinos Varvagiannis reviewed gene: UFM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28931644, 29868776; Phenotypes: Leukodystrophy hypomyelinating 14, 617899; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.972 UFM1 Konstantinos Varvagiannis Deleted their review
Intellectual disability v2.550 UFM1 Konstantinos Varvagiannis reviewed gene: UFM1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28931644, 29868776; Phenotypes: Leukodystrophy hypomyelinating 14, 617899; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v2.550 UFM1 Konstantinos Varvagiannis Deleted their review
Early onset or syndromic epilepsy v0.972 UFM1 Konstantinos Varvagiannis gene: UFM1 was added
gene: UFM1 was added to Genetic epilepsy syndromes. Sources: Literature,Expert Review
Mode of inheritance for gene: UFM1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: UFM1 were set to 28931644; 29868776
Phenotypes for gene: UFM1 were set to Leukodystrophy hypomyelinating 14, 617899
Penetrance for gene: UFM1 were set to Complete
Review for gene: UFM1 was set to GREEN
Added comment: Biallelic UFM1 mutations cause Leukodystrophy hypomyelinating 14, MIM 617899.

PMID: 28931644 is the first report on 16 individuals from 14 families with shared Roma ethnic background. All subjects were found to harbor a UFM1 promoter 3 basepair deletion in the homozygous state.

All patients demonstrated a severe phenotype including lack of development and severe epileptic encephalopathy while their MRI images demonstrated hypomyelination with atrophy of the basal ganglia and the cerebellum.

The promoter deletion was detected by exome sequencing. Previously a 0.8 Mb homozygous region (encompassing UFM1) was identified to be shared by all the patients in whom a SNP array was performed. Alternative causes, notably TUBB4A mutations and deletions/duplications were excluded. 3 individuals had Sanger sequencing of all coding regions within the homozygous interval to rule out other - eventually missed - variants.

PMID: 29868776 reports 4 additional individuals from 2 consanguineous families (one from Ethiopia, for the other this was not specified). All 4 patients were homozygous for the c.241C>T (NM_016617.3) or p.(Arg81Cys) variant which was shown to be hypomorphic upon functional studies.

The phenotype consisted of developmental delay (4/4 or 20/20 including the patients from the previous report with which comparison is made in table 2 of the article) with microcephaly (4/4 or 20/20) and seizures (4/4 or 16/20) as well as MRI abnormalities. Failure to thrive and/or short stature were also among the most common features.

UFM1 (as well as UFC1 also discussed in the same article) participate in ufmylation, with mutations in other enzymes of the same process (notably UBA5 - gene rated Green in the ID and epilepsy panels) having already been described in neurodevelopmental disorders.

As a result, this gene can be considered for inclusion in this panel as green (or amber).
Sources: Literature, Expert Review
Early onset or syndromic epilepsy v0.972 GLB1 Louise Daugherty Added comment: Comment on phenotypes: Added phenotype suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Early onset or syndromic epilepsy v0.972 GLB1 Louise Daugherty Phenotypes for gene: GLB1 were changed from to GM1-gangliosidosis, type II, 230600; seizures
Intellectual disability v2.550 UFM1 Konstantinos Varvagiannis gene: UFM1 was added
gene: UFM1 was added to Intellectual disability. Sources: Literature,Expert Review
Mode of inheritance for gene: UFM1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: UFM1 were set to 28931644; 29868776
Phenotypes for gene: UFM1 were set to Leukodystrophy hypomyelinating 14, 617899
Penetrance for gene: UFM1 were set to Complete
Review for gene: UFM1 was set to GREEN
Added comment: Biallelic UFM1 mutations cause Leukodystrophy hypomyelinating 14, MIM 617899.

PMID: 28931644 is the first report on 16 individuals from 14 families with shared Roma ethnic background. All subjects were found to harbor a UFM1 promoter 3 basepair deletion in the homozygous state.

All patients demonstrated a severe phenotype including lack of development and severe epileptic encephalopathy while their MRI images demonstrated hypomyelination with atrophy of the basal ganglia and the cerebellum.

The promoter deletion was detected by exome sequencing. Previously a 0.8 Mb homozygous region was identified to be shared by all the patients in whom a SNP array was performed. Alternative causes, notably TUBB4A mutations and deletions/duplications were excluded. 3 individuals had Sanger sequencing of all coding regions within the homozygous interval to rule out other - eventually missed - variants.

PMID: 29868776 reports 4 additional individuals from 2 consanguineous families (one from Ethiopia, for the other this was not specified). All 4 patients were homozygous for the c.241C>T (NM_016617.3) or p.(Arg81Cys) variant which was shown to be hypomorphic upon functional studies.

The phenotype consisted of developmental delay (4/4 or 20/20 including the patients from the previous report with which comparison is made in table 2 of the article) with microcephaly (4/4 or 20/20) and seizures (4/4 or 16/20) as well as MRI abnormalities. Failure to thrive and/or short stature were also among the most common features.

UFM1 (as well as UFC1 also discussed in the same article) participate in ufmylation, with mutations in other enzymes of the same process (notably UBA5 - gene rated Green in the ID and epilepsy panels) having already been described in neurodevelopmental disorders.

As a result, this gene can be considered for inclusion in this panel as green (or amber).
Sources: Literature, Expert Review
Early onset or syndromic epilepsy v0.971 GLB1 Louise Daugherty Mode of inheritance for gene: GLB1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.970 D2HGDH Rebecca Foulger Mode of inheritance for gene: D2HGDH was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.969 D2HGDH Rebecca Foulger Phenotypes for gene: D2HGDH were changed from to D-2-hydroxyglutaric aciduria, 600721
Intellectual disability v2.550 GLB1 Louise Daugherty Publications for gene: GLB1 were set to
Short QT syndrome v1.0 Sarah Leigh promoted panel to version 1.0
Early onset or syndromic epilepsy v0.968 GLDC Louise Daugherty Marked gene: GLDC as ready
Early onset or syndromic epilepsy v0.968 GLDC Louise Daugherty Gene: gldc has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.968 GLDC Louise Daugherty Classified gene: GLDC as Green List (high evidence)
Early onset or syndromic epilepsy v0.968 GLDC Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association
Early onset or syndromic epilepsy v0.968 GLDC Louise Daugherty Gene: gldc has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.967 GLDC Louise Daugherty Added comment: Comment on publications: Added publications to support upgrading of the gene to Green
Early onset or syndromic epilepsy v0.967 GLDC Louise Daugherty Publications for gene: GLDC were set to
Early onset or syndromic epilepsy v0.966 CTSD Rebecca Foulger Marked gene: CTSD as ready
Early onset or syndromic epilepsy v0.966 CTSD Rebecca Foulger Gene: ctsd has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.966 CTSD Rebecca Foulger Classified gene: CTSD as Green List (high evidence)
Early onset or syndromic epilepsy v0.966 CTSD Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green. Epileptic seizures are an accepted phenotype of CLN10 disease (MIM:610127). Epilepsy reported as part of the symptoms in at least 2 families in literature (PMID:16670177 and PMID:26059544) PLUS animal model of epilepsy (PMID:10995834). Therefore 2 cases + clear animal model is sufficient evidence for diagnostic rating.
Early onset or syndromic epilepsy v0.966 CTSD Rebecca Foulger Gene: ctsd has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.965 CTSD Rebecca Foulger commented on gene: CTSD: PMID:26059544 (Meyer et al 2015) report 2 siblings with CLN10 disease who showed intractable seizures and respiratory insufficiency immediately after birth. A homozygous insertion (c.268_269insC) in exon 3 of the cathepsin D gene was found in both infants.
Early onset or syndromic epilepsy v0.965 CTSD Rebecca Foulger commented on gene: CTSD: Animal mode: CatD-deficient mice develop seizures and progressive retinal atrophy, becoming blind (See PMIDs:10995834 and 16685649).
Early onset or syndromic epilepsy v0.965 CTSD Rebecca Foulger commented on gene: CTSD
Early onset or syndromic epilepsy v0.965 CTSD Rebecca Foulger Publications for gene: CTSD were set to
Early onset or syndromic epilepsy v0.964 KRAS Ivone Leong Phenotypes for gene: KRAS were changed from to Cardiofaciocutaneous syndrome 2, 615278
Early onset or syndromic epilepsy v0.963 KIF5C Ivone Leong Classified gene: KIF5C as Green List (high evidence)
Early onset or syndromic epilepsy v0.963 KIF5C Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. Phenotype is confirmed in both OMIM and Gene2Phenotype.
There are 3 studies (PMID: 23603762, 23033978, 29048727) that have reported, in total, 3 unrelated families (5 patients) who have various missense variants in this gene who have Cortical dysplasia and also seizures.
Early onset or syndromic epilepsy v0.963 KIF5C Ivone Leong Gene: kif5c has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.962 GLDC Louise Daugherty Mode of inheritance for gene: GLDC was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.961 GLDC Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Early onset or syndromic epilepsy v0.961 GLDC Louise Daugherty Phenotypes for gene: GLDC were changed from to Glycine encephalopathy, 605899; seizures
Early onset or syndromic epilepsy v0.960 KIF5C Ivone Leong Publications for gene: KIF5C were set to
Early onset or syndromic epilepsy v0.959 GLUD1 Louise Daugherty Marked gene: GLUD1 as ready
Early onset or syndromic epilepsy v0.959 GLUD1 Louise Daugherty Gene: glud1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.959 GLUD1 Louise Daugherty Classified gene: GLUD1 as Green List (high evidence)
Early onset or syndromic epilepsy v0.959 GLUD1 Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association.
Early onset or syndromic epilepsy v0.959 GLUD1 Louise Daugherty Gene: glud1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.958 GLUD1 Louise Daugherty Phenotypes for gene: GLUD1 were changed from Hyperinsulinism-hyperammonemia syndrome, 606762 to Hyperinsulinism-hyperammonemia syndrome, 606762; epilepsy
Early onset or syndromic epilepsy v0.957 GLUD1 Louise Daugherty Publications for gene: GLUD1 were set to 19046187
Early onset or syndromic epilepsy v0.956 CTSD Rebecca Foulger Mode of inheritance for gene: CTSD was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.955 CTSD Rebecca Foulger Phenotypes for gene: CTSD were changed from to Ceroid lipofuscinosis, neuronal, 10, 610127
Early onset or syndromic epilepsy v0.954 GLUL Louise Daugherty Marked gene: GLUL as ready
Early onset or syndromic epilepsy v0.954 GLUL Louise Daugherty Gene: glul has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.954 GLUL Louise Daugherty Added comment: Comment on publications: Added publications to support upgrading of the gene to Green
Early onset or syndromic epilepsy v0.954 GLUL Louise Daugherty Publications for gene: GLUL were set to
Early onset or syndromic epilepsy v0.953 GLUL Louise Daugherty Classified gene: GLUL as Green List (high evidence)
Early onset or syndromic epilepsy v0.953 GLUL Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association.
Early onset or syndromic epilepsy v0.953 GLUL Louise Daugherty Gene: glul has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.952 KIF5C Ivone Leong Mode of inheritance for gene: KIF5C was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v0.951 KIF5C Ivone Leong Phenotypes for gene: KIF5C were changed from to Cortical dysplasia, complex, with other brain malformations 2, 615282
Intellectual disability v2.549 CSNK2B Rebecca Foulger Phenotypes for gene: CSNK2B were changed from to Intellectual disability with or without myoclonic epilepsy
Early onset or syndromic epilepsy v0.950 KCTD3 Ivone Leong Marked gene: KCTD3 as ready
Early onset or syndromic epilepsy v0.950 KCTD3 Ivone Leong Gene: kctd3 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.950 KCTD3 Ivone Leong Classified gene: KCTD3 as Green List (high evidence)
Early onset or syndromic epilepsy v0.950 KCTD3 Ivone Leong Added comment: Comment on list classification: Promoted from amber to green. No phenotypes are associated with this gene OMIM or Gene2Phenotype.
One study (PMID: 29406573) reported various mutations in this gene for 7 probands from 4 consanguineous families who all have epilepsy. The families are from the same geographical location. The study did show that the variants segregated with the phenotype. Two other large (PMID: 27848944, 25558065) screening studies reported 3 probands with frameshift variants in this gene who have epilepsy.
Early onset or syndromic epilepsy v0.950 KCTD3 Ivone Leong Gene: kctd3 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.949 GLUD1 Louise Daugherty Added comment: Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel
Early onset or syndromic epilepsy v0.949 GLUD1 Louise Daugherty Phenotypes for gene: GLUD1 were changed from to Hyperinsulinism-hyperammonemia syndrome, 606762
Intellectual disability v2.548 CSNK2B Rebecca Foulger Publications for gene: CSNK2B were set to 28585349, 28762608
Early onset or syndromic epilepsy v0.948 GLUD1 Louise Daugherty Added comment: Comment on publications: Added publications suggested from external expert review to support upgrading of the gene to Green
Early onset or syndromic epilepsy v0.948 GLUD1 Louise Daugherty Publications for gene: GLUD1 were set to
Early onset or syndromic epilepsy v0.947 GLUD1 Louise Daugherty Added comment: Comment on mode of inheritance: Changed MOI from external clinical review and publications
Early onset or syndromic epilepsy v0.947 GLUD1 Louise Daugherty Mode of inheritance for gene: GLUD1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v2.547 CSNK2B Rebecca Foulger Classified gene: CSNK2B as Green List (high evidence)
Intellectual disability v2.547 CSNK2B Rebecca Foulger Added comment: Comment on list classification: Updated rating from Red to Green: As summarised by Zornitza, three unrelated patients reported in the literature (one in PMID:28762608 and two in PMID:28585349) with intellectual disability and de novo variants in CSNK2B (splice variant and a frameshift truncating variant). Two of the patients also had monoclonic epilepsy.
Intellectual disability v2.547 CSNK2B Rebecca Foulger Gene: csnk2b has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v0.946 KCTD3 Ivone Leong Phenotypes for gene: KCTD3 were changed from to No OMIM number; Epileptic encephalopathy
Intellectual disability v2.546 CSNK2B Rebecca Foulger Mode of inheritance for gene: CSNK2B was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v0.945 KCTD3 Ivone Leong Publications for gene: KCTD3 were set to
Early onset or syndromic epilepsy v0.944 KCTD3 Ivone Leong Mode of inheritance for gene: KCTD3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v0.943 UFC1 Konstantinos Varvagiannis gene: UFC1 was added
gene: UFC1 was added to Genetic epilepsy syndromes. Sources: Literature,Expert Review
Mode of inheritance for gene: UFC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UFC1 were set to 29868776
Phenotypes for gene: UFC1 were set to Neurodevelopmental disorder with spasticity and poor growth, 618076
Penetrance for gene: UFC1 were set to Complete
Review for gene: UFC1 was set to GREEN
Added comment: Biallelic UFC1 mutations cause Neurodevelopmental disorder with spasticity and poor growth, MIM 618076.

PMID: 29868776 describes 7 individuals (most) born to consanguineous Saudi families (in one case the parents were not consanguineous but originated from the same tribe) as well as a further individual born to distantly related Swiss parents. One of these patients was previously briefly published by the same authors (PMID: 27431290).

The phenotype consisted of developmental delay (8/8 - usually profound), failure to thrive (8/8), short stature and microcephaly (both observed in 7/8), seizures (4/8) and variable brain MRI anomalies in some of these subjects.

Overall, two UFC1 missense variants are reported [NM_016406.3:c.317C>T or p.(Thr106Ile) and c.68G>A or p.(Arg23Gln) the former in the Saudi individuals]. Functional studies demonstrated the hypomorphic nature of the variants.

UFC1 (as well as UFM1 also discussed in the same article) participate in ufmylation, with mutations in other enzymes of the same process (notably UBA5 - gene rated Green in the ID and epilepsy panels) having already been described in neurodevelopmental disorders.

Epilepsy was a feature in 50% (4/8) of the individuals reported.

As a result this gene can be considered for inclusion in the epilepsy panel as green (or amber).
Sources: Literature, Expert Review
Intellectual disability v2.545 UFC1 Konstantinos Varvagiannis gene: UFC1 was added
gene: UFC1 was added to Intellectual disability. Sources: Literature,Expert Review
Mode of inheritance for gene: UFC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UFC1 were set to 29868776
Phenotypes for gene: UFC1 were set to Neurodevelopmental disorder with spasticity and poor growth, 618076
Penetrance for gene: UFC1 were set to Complete
Review for gene: UFC1 was set to GREEN
Added comment: Biallelic UFC1 mutations cause Neurodevelopmental disorder with spasticity and poor growth, MIM 618076.

PMID: 29868776 describes 7 individuals (most) born to consanguineous Saudi families (in one case the parents were not consanguineous but originated from the same tribe) as well as a further individual born to distantly related Swiss parents. One of these patients was previously briefly published by the same authors (PMID: 27431290).

The phenotype consisted of developmental delay (8/8 - usually profound), failure to thrive (8/8), short stature and microcephaly (both observed in 7/8), seizures (4/8) and variable brain MRI anomalies in some of these subjects.

Overall, two UFC1 missense variants are reported [NM_016406.3:c.317C>T or p.(Thr106Ile) and c.68G>A or p.(Arg23Gln) the former in the Saudi individuals]. Functional studies demonstrated the hypomorphic nature of the variants.

UFC1 (as well as UFM1 also discussed in the same article) participate in ufmylation, with mutations in other enzymes of the same process (notably UBA5 - gene rated Green in the ID and epilepsy panels) having already been described in neurodevelopmental disorders.

As a result this gene can be considered for inclusion in the ID panel as green (or amber).
Sources: Literature, Expert Review
Early onset or syndromic epilepsy v0.943 KCNQ5 Ivone Leong Marked gene: KCNQ5 as ready
Early onset or syndromic epilepsy v0.943 KCNQ5 Ivone Leong Added comment: Comment when marking as ready: Phenotype conformed on OMIM and Gene2Phenotype. KCNQ5 is a green gene on the Intellectual disability panel.

As stated by Zornitza Stark (Australian Genomics), the original paper (PMID: 28669405) describes 2 of 4 patients with variants in this gene who have seizures (both are are South East Asian decent). Another paper (PMID: 30359776) describes a patient with an intragenic duplication variant in this gene who has seizures. However, as there's just not quit nough evidence I have put the Watchlist tag on.
Early onset or syndromic epilepsy v0.943 KCNQ5 Ivone Leong Gene: kcnq5 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.943 KCNQ5 Ivone Leong Tag watchlist tag was added to gene: KCNQ5.
Early onset or syndromic epilepsy v0.943 CSNK2B Rebecca Foulger Marked gene: CSNK2B as ready
Early onset or syndromic epilepsy v0.943 CSNK2B Rebecca Foulger Added comment: Comment when marking as ready: Marked as Ready: November 19th 2018.
Early onset or syndromic epilepsy v0.943 CSNK2B Rebecca Foulger Gene: csnk2b has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.943 CSNK2B Rebecca Foulger commented on gene: CSNK2B: Added watchlist tag.
Early onset or syndromic epilepsy v0.943 CSNK2B Rebecca Foulger Tag watchlist tag was added to gene: CSNK2B.
Early onset or syndromic epilepsy v0.943 CSNK2B Rebecca Foulger Classified gene: CSNK2B as Amber List (moderate evidence)
Early onset or syndromic epilepsy v0.943 CSNK2B Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber: As summarised by Zornitza, currently 2 epileptic patients with de novo CSNK2B variants (PMID:28762608 and PMID:28585349). The third patient was reported with intellectual disability but not epilepsy. At least one further epileptic case required for diagnostic rating.
Early onset or syndromic epilepsy v0.943 CSNK2B Rebecca Foulger Gene: csnk2b has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v0.942 CSNK2B Rebecca Foulger commented on gene: CSNK2B
Early onset or syndromic epilepsy v0.942 CSNK2B Rebecca Foulger Phenotypes for gene: CSNK2B were changed from to Myoclonic epilepsy and intellectual disability
Early onset or syndromic epilepsy v0.941 CSNK2B Rebecca Foulger Publications for gene: CSNK2B were set to