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Paediatric disorders - additional genes v3.9 NOTCH3 Arina Puzriakova Classified gene: NOTCH3 as Amber List (moderate evidence)
Paediatric disorders - additional genes v3.9 NOTCH3 Arina Puzriakova Gene: notch3 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v3.8 NOTCH3 Arina Puzriakova gene: NOTCH3 was added
gene: NOTCH3 was added to Paediatric disorders - additional genes. Sources: NHS GMS
Q4_23_promote_green, Q4_23_expert_review tags were added to gene: NOTCH3.
Mode of inheritance for gene: NOTCH3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOTCH3 were set to 25394726
Phenotypes for gene: NOTCH3 were set to Lateral meningocele syndrome, OMIM:130720
Mode of pathogenicity for gene: NOTCH3 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: NOTCH3 was set to GREEN
Added comment: Monoallelic variants in the NOTCH3 gene are associated with multiple phenotypes including CADASIL (MIM# 125310), Lateral Meningocele syndrome (MIM# 130720), and Myofibromatosis (MIM# 615293).

Currently, CADASIL and myofibromatosis phenotypes are covered by several PanelApp panels; however, Lateral Meningocele syndrome is not - there is enough evidence to support inclusion of this gene-disease association on a diagnostic-grade panel.

At least 5 unrelated de novo cases have been reported in literature (PMID: 25394726). All variants are truncating and cluster in the last exon of NOTCH3. Truncated proteins are predicted to cause increased notch signalling.
An additional case was identified in Genomics England's Clinical Variant Archive (CVA) dataset via the Diagnostic Discovery initiative. The participant was recruited with Lateral Meningocele syndrome (inclusive of hypertelorism, high palate, dural ectasia, high pitched voice) and a diagnostically reported variant in the last exon of this gene was returned, lending further support to adding this gene to the panel.

R27 appears to be the most phenotypically relevant panel for detecting Lateral Meningocele syndrome; however, the possibility of incidental findings of CADASIL needs to be considered. Both phenotypes are caused by GoF variants but those associated with CADASIL are located in exons 2-24 whereas variants in Lateral Meningocele found in exon 33 (last exon).

Given the risk of incidental findings without a mechanism to delineate the types of variants that are prioritised via each panel, the best route for inclusion of Lateral Meningocele syndrome in PanelApp will be flagged for further NHSE expert discussion at the next GMS panel update release.
Sources: NHS GMS
Paediatric disorders - additional genes v3.5 PAPPA2 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: PAPPA2.
Paediatric disorders - additional genes v3.5 PAPPA2 Achchuthan Shanmugasundram commented on gene: PAPPA2
Paediatric disorders - additional genes v3.5 TOR1AIP1 Arina Puzriakova Tag Q4_22_promote_green was removed from gene: TOR1AIP1.
Paediatric disorders - additional genes v3.5 PLXND1 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: PLXND1.
Paediatric disorders - additional genes v3.5 PAPPA2 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: PAPPA2.
Paediatric disorders - additional genes v3.5 FOXI3 Arina Puzriakova Tag Q4_22_promote_green was removed from gene: FOXI3.
Paediatric disorders - additional genes v3.5 TOR1AIP1 Arina Puzriakova commented on gene: TOR1AIP1: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Paediatric disorders - additional genes v3.5 PLXND1 Arina Puzriakova reviewed gene: PLXND1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric disorders - additional genes v3.5 PAPPA2 Arina Puzriakova edited their review of gene: PAPPA2: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Paediatric disorders - additional genes v3.5 FOXI3 Arina Puzriakova commented on gene: FOXI3: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.
Paediatric disorders - additional genes v3.4 TOR1AIP1 Arina Puzriakova Source Expert Review Green was added to TOR1AIP1.
Source NHS GMS was added to TOR1AIP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v3.4 PLXND1 Arina Puzriakova Source Expert Review Green was added to PLXND1.
Source NHS GMS was added to PLXND1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v3.4 PAPPA2 Arina Puzriakova Source Expert Review Green was added to PAPPA2.
Source NHS GMS was added to PAPPA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v3.4 FOXI3 Arina Puzriakova Source Expert Review Green was added to FOXI3.
Source NHS GMS was added to FOXI3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v3.3 FOXL2 Arina Puzriakova commented on gene: FOXL2: Helen Brittain (Genomics England Clinical Team) supports inclusion of BPES and blepharophimosis genes on this panel as these are features that would be considered under the dysmorphism indication.
Paediatric disorders - additional genes v3.3 TAB2 Arina Puzriakova Entity copied from Paediatric or syndromic cardiomyopathy v3.15
Paediatric disorders - additional genes v3.3 TAB2 Arina Puzriakova gene: TAB2 was added
gene: TAB2 was added to Paediatric disorders - additional genes. Sources: Expert Review Amber,NHS GMS,London South GLH
Q3_23_promote_green tags were added to gene: TAB2.
Mode of inheritance for gene: TAB2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TAB2 were set to 28464518; 29700987; 32183715; 34456334; 34990405; 34741306; 36000780; 37153890
Phenotypes for gene: TAB2 were set to Congenital heart defects, nonsyndromic, 2, OMIM:614980
Paediatric disorders - additional genes v3.2 WNT9B Arina Puzriakova Entity copied from Fetal anomalies v3.78
Paediatric disorders - additional genes v3.2 WNT9B Arina Puzriakova gene: WNT9B was added
gene: WNT9B was added to Paediatric disorders - additional genes. Sources: Literature,Expert Review Amber
watchlist tags were added to gene: WNT9B.
Mode of inheritance for gene: WNT9B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WNT9B were set to 34145744
Phenotypes for gene: WNT9B were set to Renal agenesis/hypoplasia/dysplasia
Paediatric disorders - additional genes v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2023-03-22
Paediatric disorders - additional genes v3.0 Arina Puzriakova promoted panel to version 3.0
Paediatric disorders - additional genes v2.9 PLXND1 Achchuthan Shanmugasundram Classified gene: PLXND1 as Amber List (moderate evidence)
Paediatric disorders - additional genes v2.9 PLXND1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (>3 unrelated cases) to be promoted to GREEN rating at the next GMS panel update.
Paediatric disorders - additional genes v2.9 PLXND1 Achchuthan Shanmugasundram Gene: plxnd1 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v2.8 PLXND1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: PLXND1.
Paediatric disorders - additional genes v2.8 PLXND1 Achchuthan Shanmugasundram gene: PLXND1 was added
gene: PLXND1 was added to Paediatric disorders - additional genes. Sources: Literature
Mode of inheritance for gene: PLXND1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXND1 were set to 35396997
Phenotypes for gene: PLXND1 were set to Truncus arteriosus, HP:0001660
Review for gene: PLXND1 was set to GREEN
Added comment: 10 individuals including four foetal cases from five unrelated families were identified with biallelic variants in PLXND1 gene and they presented with cardiac defects. The most frequent defect is common arterial trunk (CAT), which is also known as truncus arteriosus, a conotruncal malformation characterized by a single vessel exiting both ventricles.

This gene has already been associated with PLXND1-related cardiac malformation syndrome with the confidence category of 'strong' in DD panel of Gene2Phenotype. However, no relevant phenotypes have been currently reported in OMIM.
Sources: Literature
Paediatric disorders - additional genes v2.7 SIX2 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: SIX2.
Paediatric disorders - additional genes v2.7 FOXP4 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: FOXP4.
Paediatric disorders - additional genes v2.7 NHLRC2 Arina Puzriakova Tag Q2_22_rating was removed from gene: NHLRC2.
Tag Q2_22_expert_review was removed from gene: NHLRC2.
Paediatric disorders - additional genes v2.7 FOXP4 Arina Puzriakova Tag Q2_21_phenotype was removed from gene: FOXP4.
Tag Q2_22_rating was removed from gene: FOXP4.
Tag Q2_22_expert_review was removed from gene: FOXP4.
Paediatric disorders - additional genes v2.7 ADAMTS19 Arina Puzriakova Tag Q2_21_rating was removed from gene: ADAMTS19.
Tag Q2_21_phenotype was removed from gene: ADAMTS19.
Tag Q2_22_expert_review was removed from gene: ADAMTS19.
Paediatric disorders - additional genes v2.7 WBP11 Arina Puzriakova Tag Q2_21_rating was removed from gene: WBP11.
Paediatric disorders - additional genes v2.7 PLVAP Arina Puzriakova Tag Q2_21_rating was removed from gene: PLVAP.
Paediatric disorders - additional genes v2.7 PLD1 Arina Puzriakova Tag Q2_21_rating was removed from gene: PLD1.
Paediatric disorders - additional genes v2.7 OTUD5 Arina Puzriakova Tag Q2_21_rating was removed from gene: OTUD5.
Paediatric disorders - additional genes v2.7 FOXL2 Arina Puzriakova Tag Q2_22_rating was removed from gene: FOXL2.
Tag Q2_22_NHS_review was removed from gene: FOXL2.
Paediatric disorders - additional genes v2.7 CTU2 Arina Puzriakova Tag Q2_21_rating was removed from gene: CTU2.
Paediatric disorders - additional genes v2.7 FGF5 Arina Puzriakova Tag Q2_21_NHS_review was removed from gene: FGF5.
Tag Q2_22_rating was removed from gene: FGF5.
Tag Q2_22_phenotype was removed from gene: FGF5.
Tag Q2_22_expert_review was removed from gene: FGF5.
Paediatric disorders - additional genes v2.7 TMEM260 Arina Puzriakova Tag Q3_22_rating was removed from gene: TMEM260.
Paediatric disorders - additional genes v2.7 SIX2 Arina Puzriakova Tag Q3_22_rating was removed from gene: SIX2.
Tag Q3_22_NHS_review was removed from gene: SIX2.
Paediatric disorders - additional genes v2.7 NHLRC2 Arina Puzriakova reviewed gene: NHLRC2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric disorders - additional genes v2.7 FOXP4 Arina Puzriakova reviewed gene: FOXP4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric disorders - additional genes v2.7 ADAMTS19 Arina Puzriakova reviewed gene: ADAMTS19: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric disorders - additional genes v2.7 WBP11 Arina Puzriakova reviewed gene: WBP11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric disorders - additional genes v2.7 PLVAP Arina Puzriakova reviewed gene: PLVAP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric disorders - additional genes v2.7 PLD1 Arina Puzriakova reviewed gene: PLD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric disorders - additional genes v2.7 OTUD5 Arina Puzriakova commented on gene: OTUD5: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Paediatric disorders - additional genes v2.7 FOXL2 Arina Puzriakova reviewed gene: FOXL2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric disorders - additional genes v2.7 CTU2 Arina Puzriakova reviewed gene: CTU2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric disorders - additional genes v2.7 FGF5 Arina Puzriakova reviewed gene: FGF5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric disorders - additional genes v2.7 TMEM260 Arina Puzriakova reviewed gene: TMEM260: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric disorders - additional genes v2.7 SIX2 Arina Puzriakova reviewed gene: SIX2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric disorders - additional genes v2.6 WBP11 Arina Puzriakova Source Expert Review Green was added to WBP11.
Source NHS GMS was added to WBP11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v2.6 TMEM260 Arina Puzriakova Source Expert Review Green was added to TMEM260.
Source NHS GMS was added to TMEM260.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v2.6 SIX2 Arina Puzriakova Source Expert Review Green was added to SIX2.
Source NHS GMS was added to SIX2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v2.6 PLVAP Arina Puzriakova Source Expert Review Green was added to PLVAP.
Source NHS GMS was added to PLVAP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v2.6 PLD1 Arina Puzriakova Source Expert Review Green was added to PLD1.
Source NHS GMS was added to PLD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v2.6 OTUD5 Arina Puzriakova Source Expert Review Green was added to OTUD5.
Source NHS GMS was added to OTUD5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v2.6 NHLRC2 Arina Puzriakova Source Expert Review Green was added to NHLRC2.
Source NHS GMS was added to NHLRC2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v2.6 FOXP4 Arina Puzriakova Source Expert Review Green was added to FOXP4.
Source NHS GMS was added to FOXP4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v2.6 FOXL2 Arina Puzriakova Source Expert Review Green was added to FOXL2.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Paediatric disorders - additional genes v2.6 FGF5 Arina Puzriakova Source NHS GMS was added to FGF5.
Paediatric disorders - additional genes v2.6 CTU2 Arina Puzriakova Source Expert Review Green was added to CTU2.
Source NHS GMS was added to CTU2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v2.6 ADAMTS19 Arina Puzriakova Source Expert Review Green was added to ADAMTS19.
Source NHS GMS was added to ADAMTS19.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v2.5 PAPPA2 Arina Puzriakova Classified gene: PAPPA2 as Amber List (moderate evidence)
Paediatric disorders - additional genes v2.5 PAPPA2 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.
Paediatric disorders - additional genes v2.5 PAPPA2 Arina Puzriakova Gene: pappa2 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v2.4 PAPPA2 Arina Puzriakova gene: PAPPA2 was added
gene: PAPPA2 was added to Paediatric disorders - additional genes. Sources: Expert list
Q1_23_promote_green tags were added to gene: PAPPA2.
Mode of inheritance for gene: PAPPA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAPPA2 were set to 26902202; 33875846; 34272725
Phenotypes for gene: PAPPA2 were set to Short stature, Dauber-Argente type, OMIM:619489
Added comment: At least 9 individuals from 5 unrelated families reported in literature with biallelic variants in this gene (PMID: 26902202; 33875846; 34272725). Clinical presentation is most notable for short stature, mild/moderate microcephaly, and dysmorphic features. Growth restriction typically becomes apparent with age.
Sources: Expert list
Paediatric disorders - additional genes v2.3 TOR1AIP1 Arina Puzriakova Classified gene: TOR1AIP1 as Amber List (moderate evidence)
Paediatric disorders - additional genes v2.3 TOR1AIP1 Arina Puzriakova Gene: tor1aip1 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v2.2 TOR1AIP1 Arina Puzriakova gene: TOR1AIP1 was added
gene: TOR1AIP1 was added to Paediatric disorders - additional genes. Sources: Expert list
Q4_22_promote_green tags were added to gene: TOR1AIP1.
Mode of inheritance for gene: TOR1AIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOR1AIP1 were set to 24856141; 25425325; 27342937; 30723199; 31299614; 32055997; 33215087; 34164833
Phenotypes for gene: TOR1AIP1 were set to Muscular dystrophy, autosomal recessive, with rigid spine and distal joint contractures, OMIM:617072
Review for gene: TOR1AIP1 was set to GREEN
Added comment: Gene was initially added to the Cardiomyopathy panel; however, after NHS GMS review it was determined that R27 (congenital malformation/syndromic) panel is more appropriate. Therefore adding here with the recommendation of upgrading to Green status at the next review.
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Associated with relevant phenotype in OMIM, but currently not in Gene2Phenotype.

At least 15 affected individuals from 10 families with biallelic variants in this gene. Of these, 7 individuals (5 families) reported in PMID:30723199 harbour the same founder variant presenting a very similar phenotype, and are therefore considered collectively here. Patients present a severe multisystem phenotype with muscular dystrophy being the prominent feature observed in at least one case in each family, but additional common features also include joint contractures (4 fam), dilated cardiomyopathy (4 fam), developmental delay (4 fam), and cataracts (3 fam).

Note that one additional homozygous case has been reported with what is thought to be a discrete phenotype characterised by progressive dystonia, cerebellar atrophy, and dilated cardiomyopathy (PMID: 25425325). Biallelic variants have also been linked to a congenital myasthenic syndrome in two unrelated families (PMID: 33215087; 34164833).
Sources: Expert list
Paediatric disorders - additional genes v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2022-11-30
Paediatric disorders - additional genes v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Paediatric disorders - additional genes v1.108 FOXI3 Arina Puzriakova Classified gene: FOXI3 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.108 FOXI3 Arina Puzriakova Added comment: Comment on list classification: This gene should be promoted to Green at the next GMS panel update.
A recent study (highlighted by GEL Clinical Team) provides corroborating evidence linking FOXI3 with microtia with or without atresia. Sufficient unrelated cases and supported by concordant animal models.
Paediatric disorders - additional genes v1.108 FOXI3 Arina Puzriakova Gene: foxi3 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.107 FOXI3 Arina Puzriakova gene: FOXI3 was added
gene: FOXI3 was added to Paediatric disorders - additional genes. Sources: Expert Review
Q4_22_promote_green tags were added to gene: FOXI3.
Mode of inheritance for gene: FOXI3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXI3 were set to 36260083; 25655429; 18787161; 24650709
Phenotypes for gene: FOXI3 were set to Bilateral Microtia; Congenital aural atresia
Review for gene: FOXI3 was set to GREEN
Added comment: Quiat et al. 2022 (PMID: 36260083) reported 4 unrelated families affected by microtia with or without atresia and different predicted deleterious heterozygous variants in the FOXI3 gene. Variants segregated with disease, including in multiplex families, albeit with reduced penetrance. In vitro studies showed that patient variants conferred abnormal FOXI3 nuclear and cytoplasmic localization.

Tassano et al. 2015 (PMID: 25655429) also identified a patient with microtia, aural atresia, and ipsilateral agenesis of the carotid artery who harboured a 2.5 Mb deletion overlapping the FOXI3 gene.

Congenital ear malformations with variable penetrance have been described in a Foxi3 knockout mouse model and haploinsufficient canine breeds supporting a role of FOXI3 in the human phenotype (PMID: 18787161; 24650709)
Sources: Expert Review
Paediatric disorders - additional genes v1.106 GDF1 Arina Puzriakova Phenotypes for gene: GDF1 were changed from Right atrial isomerism (Ivemark), 208530; Congenital heart defects, multiple types, 6, 613854 to Congenital heart defects, multiple types, 6, OMIM:613854; Right atrial isomerism (Ivemark), OMIM:208530
Paediatric disorders - additional genes v1.105 TMEM260 Eleanor Williams changed review comment from: Copied this gene from the Fetal anomilies/DDG2P panel on the advice on the Genomics England Clinical team as it is relevant to the Paediatric disorders super panel. If it is updated in an update of the DDG2P panel then it is not needed here, but otherwise is on this panel so that it will appear in the super panel.; to: Copied this gene from the Fetal anomilies/DDG2P panel on the advice on the Genomics England Clinical team as it is relevant to the Paediatric disorders super panel. If it is updated in an update of the DDG2P panel then it is not needed here, but otherwise is on this panel so that it will appear in the super panel.

It should be rated green following the next review.
Paediatric disorders - additional genes v1.105 TMEM260 Eleanor Williams commented on gene: TMEM260
Paediatric disorders - additional genes v1.105 TMEM260 Eleanor Williams Tag Q4_21_rating was removed from gene: TMEM260.
Tag Q3_22_rating tag was added to gene: TMEM260.
Paediatric disorders - additional genes v1.105 TMEM260 Eleanor Williams Entity copied from Fetal anomalies v1.877
Paediatric disorders - additional genes v1.105 TMEM260 Eleanor Williams gene: TMEM260 was added
gene: TMEM260 was added to Paediatric disorders - additional genes. Sources: Expert Review Amber,PAGE DD-Gene2Phenotype
Q4_21_rating tags were added to gene: TMEM260.
Mode of inheritance for gene: TMEM260 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM260 were set to 28318500; 34612517
Phenotypes for gene: TMEM260 were set to Structural heart defects and renal anomalies syndrome, OMIM:617478; Structural heart defects and renal anomalies syndrome, MONDO:0044321
Paediatric disorders - additional genes v1.104 ZFPM2 Arina Puzriakova Phenotypes for gene: ZFPM2 were changed from Tetralogy of Fallot to Tetralogy of Fallot, OMIM:187500
Paediatric disorders - additional genes v1.103 SIX2 Sarah Leigh changed review comment from: Not associated with a phenotype in OMIM or Gen2Phen, but it is associated with six2-related frontonasal dysplasia in MONDO / ORPHA:488437. At least 4 unrelated cases of haplosufficiency of SIX2 have been reported (three published and one in a patient reported by Julie Evans (South West Genomic Laboratory Hub)).; to: Not associated with a phenotype in OMIM or Gen2Phen, but it is associated with six2-related frontonasal dysplasia in MONDO / ORPHA:488437. At least 4 unrelated cases of haplosufficiency of SIX2 have been reported (three published and one in a patient reported by Julie Evans (South West Genomic Laboratory Hub)). So far the variants associated with SIX2 are deletions of varying sizes, with the common feature that they all encompass the SIX2 locus.
Paediatric disorders - additional genes v1.103 SIX2 Sarah Leigh Tag structural-variant tag was added to gene: SIX2.
Paediatric disorders - additional genes v1.103 SIX2 Sarah Leigh Phenotypes for gene: SIX2 were changed from Frontonasal dysplasia; ptosis; hearing loss to six2-related frontonasal dysplasia, MONDO:0044628
Paediatric disorders - additional genes v1.102 SIX2 Sarah Leigh edited their review of gene: SIX2: Added comment: Not associated with a phenotype in OMIM or Gen2Phen, but it is associated with six2-related frontonasal dysplasia in MONDO / ORPHA:488437. At least 4 unrelated cases of haplosufficiency of SIX2 have been reported (three published and one in a patient reported by Julie Evans (South West Genomic Laboratory Hub)).; Changed rating: GREEN; Changed phenotypes to: six2-related frontonasal dysplasia, MONDO:0044628
Paediatric disorders - additional genes v1.102 SIX2 Sarah Leigh Classified gene: SIX2 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.102 SIX2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Paediatric disorders - additional genes v1.102 SIX2 Sarah Leigh Gene: six2 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.101 SIX2 Sarah Leigh Tag Q3_22_rating tag was added to gene: SIX2.
Tag Q3_22_NHS_review tag was added to gene: SIX2.
Paediatric disorders - additional genes v1.101 SIX2 Sarah Leigh Publications for gene: SIX2 were set to PMID: 27383657; 29315086; 26581443
Paediatric disorders - additional genes v1.100 SIX2 Sarah Leigh Classified gene: SIX2 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.100 SIX2 Sarah Leigh Gene: six2 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.99 FGF5 Eleanor Williams Classified gene: FGF5 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.99 FGF5 Eleanor Williams Gene: fgf5 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.98 FGF5 Eleanor Williams changed review comment from: This gene was originally added to the DDG2P panel but this gene is not present in the Gene2Phenotype resource. After review by a Genomics England clinician it was decided that this may be the best place for this gene as there is no specific hypertrichosis panel. Rating amber but with a recommendation for green rating if after GMS review it is considered appropriate for this panel.; to: This gene was originally added to the DDG2P panel but this gene is not present in the Developmental Disorders panel in the Gene2Phenotype resource which DDG2P panel reflects.

After review by a Genomics England clinician it was decided that this may be the best place for this gene as there is no specific hypertrichosis panel. Rating amber but with a recommendation for green rating if after GMS review it is considered appropriate for this panel.
Paediatric disorders - additional genes v1.98 FGF5 Eleanor Williams commented on gene: FGF5
Paediatric disorders - additional genes v1.98 FGF5 Eleanor Williams Deleted their review
Paediatric disorders - additional genes v1.98 FGF5 Eleanor Williams Tag Q2_21_NHS_review tag was added to gene: FGF5.
Tag Q2_22_rating tag was added to gene: FGF5.
Tag Q2_22_phenotype tag was added to gene: FGF5.
Tag Q2_22_expert_review tag was added to gene: FGF5.
Paediatric disorders - additional genes v1.98 FGF5 Eleanor Williams Entity copied from DDG2P v2.74
Paediatric disorders - additional genes v1.98 FGF5 Eleanor Williams gene: FGF5 was added
gene: FGF5 was added to Paediatric disorders - additional genes. Sources: Literature
Mode of inheritance for gene: FGF5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FGF5 were set to PMID: 24989505
Phenotypes for gene: FGF5 were set to Hypertrichosis; long eyelashes
Penetrance for gene: FGF5 were set to Complete
Paediatric disorders - additional genes v1.97 FOXL2 Catherine Snow changed review comment from: Suitable number of cases with pathogenic variants associated with condition. Gene associated with 2 forms of blepharophimosis/ptosis/epicanthus inversus syndrome. Type 1, eyelid abnormalities are associated with ovarian failure. Type 2 has eyelid abnormalities. As other genes associated with blepharophimosis are not on this panel querying clinical team to see if gene phenotype if suitable for panel.; to: Suitable number of cases with pathogenic variants associated with condition. Gene associated with 2 forms of blepharophimosis/ptosis/epicanthus inversus syndrome. Type 1, eyelid abnormalities are associated with ovarian failure. Type 2 has eyelid abnormalities. As other genes associated with blepharophimosis are not on this panel querying clinical team to see if gene phenotype if suitable for panel.
Following feedback from clinical team this will become Green.
Paediatric disorders - additional genes v1.97 FOXL2 Catherine Snow Tag Q2_22_rating tag was added to gene: FOXL2.
Tag Q2_22_NHS_review tag was added to gene: FOXL2.
Paediatric disorders - additional genes v1.97 ADAMTS19 Sarah Leigh Tag Q2_22_expert_review tag was added to gene: ADAMTS19.
Paediatric disorders - additional genes v1.97 FOXP4 Sarah Leigh reviewed gene: FOXP4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Paediatric disorders - additional genes v1.97 FOXP4 Sarah Leigh Tag Q2_22_rating tag was added to gene: FOXP4.
Tag Q2_22_expert_review tag was added to gene: FOXP4.
Paediatric disorders - additional genes v1.97 SIX2 Julie Evans gene: SIX2 was added
gene: SIX2 was added to Paediatric disorders - additional genes. Sources: Literature
Mode of inheritance for gene: SIX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SIX2 were set to PMID: 27383657; 29315086; 26581443
Phenotypes for gene: SIX2 were set to Frontonasal dysplasia; ptosis; hearing loss
Penetrance for gene: SIX2 were set to unknown
Review for gene: SIX2 was set to GREEN
Added comment: We have a patient with a de novo deletion of the whole SIX2 gene with a compatible phenotype to the published cases (hypertelorism, ptosis, conductive hearing loss, large fontanelle).
Sources: Literature
Paediatric disorders - additional genes v1.97 FOXL2 Eleanor Williams Tag Q2_22_phenotype was removed from gene: FOXL2.
Tag Q2_22_expert_review was removed from gene: FOXL2.
Tag Q2_22_NHS_review was removed from gene: FOXL2.
Paediatric disorders - additional genes v1.97 FOXL2 Eleanor Williams Classified gene: FOXL2 as Red List (low evidence)
Paediatric disorders - additional genes v1.97 FOXL2 Eleanor Williams Added comment: Comment on list classification: Promoting from grey to red for just now. Sufficient evidence for a gene-disease association if the phenotype is appropriate for the panel. Waiting for feedback from the clinical team.
Paediatric disorders - additional genes v1.97 FOXL2 Eleanor Williams Gene: foxl2 has been classified as Red List (Low Evidence).
Paediatric disorders - additional genes v1.96 FOXL2 Catherine Snow Tag Q2_22_phenotype tag was added to gene: FOXL2.
Tag Q2_22_expert_review tag was added to gene: FOXL2.
Tag Q2_22_NHS_review tag was added to gene: FOXL2.
Paediatric disorders - additional genes v1.96 FOXL2 Catherine Snow changed review comment from: Suitable number of cases with pathogenic variants associated with condition. Gene associated with 2 forms of blepharophimosis/ptosis/epicanthus inversus syndrome. Type 1, eyelid abnormalities are associated with ovarian failure. Type 2 has eyelid abnormalities. As other genes associated with blepharophimosis are not on this panel querying clinical tam to see if gene phenotype if suitable for panel; to: Suitable number of cases with pathogenic variants associated with condition. Gene associated with 2 forms of blepharophimosis/ptosis/epicanthus inversus syndrome. Type 1, eyelid abnormalities are associated with ovarian failure. Type 2 has eyelid abnormalities. As other genes associated with blepharophimosis are not on this panel querying clinical team to see if gene phenotype if suitable for panel.
Paediatric disorders - additional genes v1.96 FOXL2 Catherine Snow reviewed gene: FOXL2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Blepharophimosis, epicanthus inversus, and ptosis, type 1 OMIM:110100; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Paediatric disorders - additional genes v1.96 WBP11 Arina Puzriakova Tag gene-checked tag was added to gene: WBP11.
Paediatric disorders - additional genes v1.96 TRAP1 Eleanor Williams Tag gene-checked tag was added to gene: TRAP1.
Paediatric disorders - additional genes v1.96 NHLRC2 Eleanor Williams Tag Q2_22_expert_review tag was added to gene: NHLRC2.
Paediatric disorders - additional genes v1.96 NHLRC2 Eleanor Williams Tag Q2_22_rating tag was added to gene: NHLRC2.
Tag gene-checked tag was added to gene: NHLRC2.
Paediatric disorders - additional genes v1.96 GREB1L Eleanor Williams Tag gene-checked tag was added to gene: GREB1L.
Paediatric disorders - additional genes v1.96 HYAL2 Arina Puzriakova Tag gene-checked tag was added to gene: HYAL2.
Paediatric disorders - additional genes v1.96 CDX1 Sarah Leigh Tag gene-checked tag was added to gene: CDX1.
Paediatric disorders - additional genes v1.96 NADSYN1 Arina Puzriakova Tag for-review was removed from gene: NADSYN1.
Paediatric disorders - additional genes v1.96 MYOCD Arina Puzriakova Tag for-review was removed from gene: MYOCD.
Paediatric disorders - additional genes v1.96 LRIG2 Arina Puzriakova Tag for-review was removed from gene: LRIG2.
Paediatric disorders - additional genes v1.96 ITGA8 Arina Puzriakova Tag for-review was removed from gene: ITGA8.
Paediatric disorders - additional genes v1.96 GREB1L Arina Puzriakova Tag for-review was removed from gene: GREB1L.
Paediatric disorders - additional genes v1.96 GATA3 Arina Puzriakova Tag for-review was removed from gene: GATA3.
Paediatric disorders - additional genes v1.96 CHRNA3 Arina Puzriakova Tag for-review was removed from gene: CHRNA3.
Paediatric disorders - additional genes v1.96 ANOS1 Arina Puzriakova Tag for-review was removed from gene: ANOS1.
Paediatric disorders - additional genes v1.96 AGT Arina Puzriakova Tag for-review was removed from gene: AGT.
Paediatric disorders - additional genes v1.96 AGTR1 Arina Puzriakova Tag for-review was removed from gene: AGTR1.
Paediatric disorders - additional genes v1.96 ACE Arina Puzriakova Tag for-review was removed from gene: ACE.
Paediatric disorders - additional genes v1.96 ACTG2 Arina Puzriakova Tag for-review was removed from gene: ACTG2.
Paediatric disorders - additional genes v1.96 TBX18 Arina Puzriakova Tag for-review was removed from gene: TBX18.
Paediatric disorders - additional genes v1.96 REN Arina Puzriakova Tag for-review was removed from gene: REN.
Paediatric disorders - additional genes v1.96 TSPYL1 Arina Puzriakova Tag for-review was removed from gene: TSPYL1.
Paediatric disorders - additional genes v1.96 STN1 Arina Puzriakova Tag for-review was removed from gene: STN1.
Paediatric disorders - additional genes v1.96 PIGQ Arina Puzriakova Tag for-review was removed from gene: PIGQ.
Paediatric disorders - additional genes v1.96 CDH2 Arina Puzriakova Tag for-review was removed from gene: CDH2.
Paediatric disorders - additional genes v1.96 RINT1 Arina Puzriakova Tag for-review was removed from gene: RINT1.
Paediatric disorders - additional genes v1.96 HYAL2 Arina Puzriakova Tag for-review was removed from gene: HYAL2.
Paediatric disorders - additional genes v1.96 NADSYN1 Sarah Leigh commented on gene: NADSYN1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Paediatric disorders - additional genes v1.96 MYOCD Sarah Leigh commented on gene: MYOCD: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Paediatric disorders - additional genes v1.96 LRIG2 Sarah Leigh commented on gene: LRIG2
Paediatric disorders - additional genes v1.96 ITGA8 Sarah Leigh commented on gene: ITGA8
Paediatric disorders - additional genes v1.96 GREB1L Sarah Leigh commented on gene: GREB1L
Paediatric disorders - additional genes v1.96 GATA3 Sarah Leigh commented on gene: GATA3
Paediatric disorders - additional genes v1.96 CHRNA3 Sarah Leigh commented on gene: CHRNA3
Paediatric disorders - additional genes v1.96 ANOS1 Sarah Leigh commented on gene: ANOS1
Paediatric disorders - additional genes v1.96 AGTR1 Sarah Leigh commented on gene: AGTR1
Paediatric disorders - additional genes v1.96 AGT Sarah Leigh commented on gene: AGT
Paediatric disorders - additional genes v1.96 ACE Sarah Leigh commented on gene: ACE
Paediatric disorders - additional genes v1.96 ACTG2 Sarah Leigh commented on gene: ACTG2
Paediatric disorders - additional genes v1.96 TBX18 Sarah Leigh commented on gene: TBX18
Paediatric disorders - additional genes v1.96 REN Sarah Leigh commented on gene: REN
Paediatric disorders - additional genes v1.96 TSPYL1 Sarah Leigh commented on gene: TSPYL1
Paediatric disorders - additional genes v1.96 STN1 Sarah Leigh commented on gene: STN1: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Paediatric disorders - additional genes v1.96 PIGQ Sarah Leigh commented on gene: PIGQ: The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Paediatric disorders - additional genes v1.96 CDH2 Sarah Leigh commented on gene: CDH2
Paediatric disorders - additional genes v1.96 RINT1 Sarah Leigh commented on gene: RINT1
Paediatric disorders - additional genes v1.96 HYAL2 Sarah Leigh commented on gene: HYAL2
Paediatric disorders - additional genes v1.95 NADSYN1 Arina Puzriakova Source Expert Review Green was added to NADSYN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v1.95 MYOCD Arina Puzriakova Source Expert Review Green was added to MYOCD.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v1.95 LRIG2 Arina Puzriakova Source Expert Review Green was added to LRIG2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v1.95 ITGA8 Arina Puzriakova Source Expert Review Green was added to ITGA8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v1.95 GREB1L Arina Puzriakova Source Expert Review Green was added to GREB1L.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v1.95 GATA3 Arina Puzriakova Source Expert Review Green was added to GATA3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v1.95 CHRNA3 Arina Puzriakova Source Expert Review Green was added to CHRNA3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v1.95 ANOS1 Arina Puzriakova Source Expert Review Green was added to ANOS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v1.95 AGTR1 Arina Puzriakova Source Expert Review Green was added to AGTR1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v1.95 AGT Arina Puzriakova Source Expert Review Green was added to AGT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v1.95 ACE Arina Puzriakova Source Expert Review Green was added to ACE.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v1.95 ACTG2 Arina Puzriakova Source Expert Review Green was added to ACTG2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v1.95 TBX18 Arina Puzriakova Source Expert Review Green was added to TBX18.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v1.95 REN Arina Puzriakova Source Expert Review Green was added to REN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v1.95 TSPYL1 Arina Puzriakova Source Expert Review Green was added to TSPYL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v1.95 STN1 Arina Puzriakova Source Expert Review Green was added to STN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v1.95 PIGQ Arina Puzriakova Source Expert Review Green was added to PIGQ.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v1.95 CDH2 Arina Puzriakova Source Expert Review Green was added to CDH2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v1.95 RINT1 Arina Puzriakova Source Expert Review Green was added to RINT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v1.95 HYAL2 Arina Puzriakova Source Expert Review Green was added to HYAL2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v1.94 FOXL2 Ronnie Wright changed review comment from: Recent request from clinician to specifically interrogate this gene from WGS data because BPES was clinically suspected in a patient and they were surprised it was not included in the R27 'congenital malformation and dysmorphism syndromes' gene list (paediatric disorders panel).
Sources: Other, NHS GMS; to: Recent request from clinician to specifically interrogate this gene from WGS data because BPES was clinically suspected in a patient and they were surprised it was not included in the R27 'congenital malformation and dysmorphism syndromes' gene list (paediatric disorders panel).
Sources: Other, NHS GMS
Paediatric disorders - additional genes v1.94 FOXL2 Ronnie Wright changed review comment from: Recent request from clinician to specifically interrogate this gene from WGS data because it was clinically suspected in a patient and they were surprised it was not included in R27 congenital malformation and dysmorphism syndromes gene list (paediatric disorders panel).
Sources: Other, NHS GMS; to: Recent request from clinician to specifically interrogate this gene from WGS data because BPES was clinically suspected in a patient and they were surprised it was not included in the R27 'congenital malformation and dysmorphism syndromes' gene list (paediatric disorders panel).
Sources: Other, NHS GMS
Paediatric disorders - additional genes v1.94 FOXL2 Ronnie Wright gene: FOXL2 was added
gene: FOXL2 was added to Paediatric disorders - additional genes. Sources: Other,NHS GMS
Mode of inheritance for gene: FOXL2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Penetrance for gene: FOXL2 were set to unknown
Review for gene: FOXL2 was set to AMBER
Added comment: Recent request from clinician to specifically interrogate this gene from WGS data because it was clinically suspected in a patient and they were surprised it was not included in R27 congenital malformation and dysmorphism syndromes gene list (paediatric disorders panel).
Sources: Other, NHS GMS
Paediatric disorders - additional genes v1.94 WBP11 Ivone Leong Phenotypes for gene: WBP11 were changed from malformation syndrome affecting the cardiac, skeletal, gastrointestinal and renal systems to Vertebral, cardiac, tracheoesophageal, renal, and limb defects, OMIM:619227
Paediatric disorders - additional genes v1.93 CTU2 Ivone Leong Entity copied from Severe microcephaly v2.146
Paediatric disorders - additional genes v1.93 CTU2 Ivone Leong gene: CTU2 was added
gene: CTU2 was added to Paediatric disorders - additional genes. Sources: Expert Review Amber,Expert list
Q2_21_rating tags were added to gene: CTU2.
Mode of inheritance for gene: CTU2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTU2 were set to 26633546; 27480277; 31301155
Phenotypes for gene: CTU2 were set to Microcephaly, facial dysmorphism, renal agenesis, and ambiguous genitalia syndrome, OMIM:618142
Paediatric disorders - additional genes v1.92 ADAMTS19 Ivone Leong Classified gene: ADAMTS19 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.92 ADAMTS19 Ivone Leong Gene: adamts19 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.91 ADAMTS19 Ivone Leong gene: ADAMTS19 was added
gene: ADAMTS19 was added to Paediatric disorders - additional genes. Sources: Literature
Q2_21_rating, Q2_21_phenotype tags were added to gene: ADAMTS19.
Mode of inheritance for gene: ADAMTS19 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS19 were set to 31844321; 32323311
Phenotypes for gene: ADAMTS19 were set to Non-syndromic heart valve disease; heart valve disease, MONDO:0002869
Review for gene: ADAMTS19 was set to AMBER
Added comment: This gene is not associated with a phenotype in OMIM or Gene2Phenotype. It is a Green gene on the Familial non syndromic congenital heart disease (Version 1.60) panel with the following reviews:

"New 2020 paper reports 3 additional consanguineous families (2 affected sibs in each) with anomalies of the aortic/pulmonary valves, which included thickening of valve leaflets, stenosis and insufficiency. All 3 families had homozygous LoF variants in ADAMTS19, which segregated with disease. No functional studies. Previously reported 4 affected in 2 unrelated consanguineous families with non-syndromic heart valve disease. 1 family with an intragenic (exon 1-8) deletion and 1 nonsense variant. Carriers unaffected. Homozygous knockout mice for Adamts19 show aortic valve dysfunction, recapitulating aspects of the human phenotype
Zornitza Stark (Australian Genomics), 1 Jul 2020"

"PMID: 31844321; Wünnemann 2020: 4 affected in 2 unrelated consanguineous families with non-syndromic heart valve disease. 1 family with an intragenic (exon 1-8) deletion and 1 nonsense variant. Carriers unaffected. Homozygous knockout mice for Adamts19 show aortic valve dysfunction, recapitulating aspects of the human phenotype Sources: Literature
Zornitza Stark (Australian Genomics), 1 May 2020"

After consulting the Genomics England Clinical Team it was decided that this gene should be added to this panel as an Amber gene and subject to GMS specialist review panel to consider whether the isolated phenotype is appropriate for inclusion. If appropriate then this gene should be promoted to Green status.
Sources: Literature
Paediatric disorders - additional genes v1.90 PLVAP Ivone Leong Classified gene: PLVAP as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.90 PLVAP Ivone Leong Gene: plvap has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.89 PLVAP Ivone Leong gene: PLVAP was added
gene: PLVAP was added to Paediatric disorders - additional genes. Sources: Literature
Q2_21_rating tags were added to gene: PLVAP.
Mode of inheritance for gene: PLVAP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLVAP were set to 29875123; 29661969; 26207260; 31215290
Phenotypes for gene: PLVAP were set to Diarrhoea 10, protein-losing enteropathy type, OMIM:618183
Review for gene: PLVAP was set to GREEN
Added comment: This gene is associated with a relevant phenotype in OMIM but not Gene2Phenotype. It is currently Amber with a recommendation to promote to Green on the Intestinal failure panel (Version 1.36) with the following reviews:

"Diarrhoea-10 is a protein-losing enteropathy characterized by intractable secretory diarrhoea and massive protein loss due to leaky fenestrated capillaries. Features include early-onset anasarca, severe hypoalbuminemia, hypogammaglobulinemia, and hypertriglyceridemia, as well as electrolyte abnormalities. Some patients exhibit facial dysmorphism and cardiac and renal anomalies. Intrafamilial variability has been observed, and the disease can be severe, with death occurring in infancy in some patients. Four unrelated families reported. Sources: Expert Review
Zornitza Stark (Australian Genomics), 5 Jan 2021"

"Comment on publications: PMID: 26207260. Patient is of Afgan descent born to consanguineous parents. Presented at 8 days of life with secretory diarrhea, metabolic acidosis, lethargy, poor feeding, and severe hyponatremia causing seizures. Further examination shows patient had bilateral colobomas, undescended testes, mildly dysplastic kidneys bilaterally, low-set ears, and micrognathia. PMID: 29875123. 2 patients (first cousins) from a Muslim Arab consanguineous kindred presented with anasarca, severe hypoalbuminaemia and hypogammaglobinaemia. PMID: 29661969. Patient is of Turkish descent born to consanguineous parents. Presented with severe haematochezia and moderate anasarca. Other findings: dysmorphism, metabolic acidosis, electrolyte deficiencies, elevated GGT, choroid plexus cysts, iris cysts, ASD, VSD, dilated megaureter with dilated renal pelvis, venous thrombosis. PMID: 31215290. Patient born to consanguineous parents. As well as intestinal phenotypes, she also had dysmorphic features, renal and cardiac phenotypes.
Ivone Leong (Genomics England Curator), 12 Apr 2021"

After discussion with the Geomics England Clinical Team it was decided that this gene should also be on this panel.
Sources: Literature
Paediatric disorders - additional genes v1.88 FOXP4 Ivone Leong Classified gene: FOXP4 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.88 FOXP4 Ivone Leong Gene: foxp4 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.87 FOXP4 Ivone Leong gene: FOXP4 was added
gene: FOXP4 was added to Paediatric disorders - additional genes. Sources: Literature
Q2_21_phenotype tags were added to gene: FOXP4.
Mode of inheritance for gene: FOXP4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXP4 were set to 33110267
Phenotypes for gene: FOXP4 were set to Neurodevelopmental disorder; multiple congenital abnormalities
Review for gene: FOXP4 was set to AMBER
Added comment: This gene is associated with a phenotype in Gene2Phenotype but not in OMIM.

This gene is present as an Amber gene on the Intellectual disability panel (Version 3.1052) with the following reviews:

"This gene is a little bit difficult to place, may be Green on Fetal Anomalies panel? Eight unrelated individuals reported, seven de novo missense, and one individual with a truncating variant. Detailed phenotypic information available on 6. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia (2/6), cervical spine abnormalities, and ptosis. Intellectual disability described as mild in 2, some had normal intellect despite the early speech and language delays, hence Amber rating here. Sources: Literature
Zornitza Stark (Australian Genomics), 4 Nov 2020"

"Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). As ID is not present in the majority of affected patients, and the affected individuals only show mild ID, this gene has been given an Amber rating.
Ivone Leong (Genomics England Curator), 4 Dec 2020"

After discussion with the Genomics England Clinical Team it was decided that this gene should be added to this panel as an Amber gene and subject to review by the GMS specialist group.
Sources: Literature
Paediatric disorders - additional genes v1.86 PLD1 Ivone Leong commented on gene: PLD1: This gene is associated with a phenotype in OMIM but not in Gene2Phenotype. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Paediatric disorders - additional genes v1.86 PLD1 Ivone Leong Phenotypes for gene: PLD1 were changed from Cardiac valvular defect, developmental to Cardiac valvular defect, developmental, OMIM:212093
Paediatric disorders - additional genes v1.85 PLD1 Ivone Leong Added comment: Comment on publications: PMID 33645542: 31 individuals from 20 families reported, presenting predominantly with congenital cardiac valve defects and some with neonatal cardiomyopathy. p.I668F is a founder variant among Ashkenazi Jews (allele frequency of ~2%). Sources: Literature
Zornitza Stark (Australian Genomics), 15 Apr 2021
Paediatric disorders - additional genes v1.85 PLD1 Ivone Leong Publications for gene: PLD1 were set to 27799408
Paediatric disorders - additional genes v1.84 PLD1 Ivone Leong Tag Q2_21_rating tag was added to gene: PLD1.
Paediatric disorders - additional genes v1.84 WBP11 Eleanor Williams Classified gene: WBP11 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.84 WBP11 Eleanor Williams Added comment: Comment on list classification: Promoting to amber but with a recommendation for green rating at the next GMS review.
Paediatric disorders - additional genes v1.84 WBP11 Eleanor Williams Gene: wbp11 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.83 WBP11 Eleanor Williams Tag Q2_21_rating tag was added to gene: WBP11.
Paediatric disorders - additional genes v1.83 WBP11 Eleanor Williams gene: WBP11 was added
gene: WBP11 was added to Paediatric disorders - additional genes. Sources: Literature
Mode of inheritance for gene: WBP11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: WBP11 were set to 33276377
Phenotypes for gene: WBP11 were set to malformation syndrome affecting the cardiac, skeletal, gastrointestinal and renal systems
Review for gene: WBP11 was set to GREEN
Added comment: PMID: 33276377 - Martin et al 2020 - report 13 affected individuals from 7 unrelated families identified through various different cohort analysis (vertebral malformation, renal hypodysplasia, syndromic esophageal atresia, multiple congenital anomalies) in whom a WBP11 heterozygous variant is considered the top causative candidate. 5 identified variants were predicted to be protein truncating whilst the 6th was a missense variant. All variants are absent from population databases. In family 1, the variant was inherited from the apparently unaffected mother, indicating reduced penetrance, and phenotypic variance within families was observed. Phenotypes covered cardiac, vertebral, renal, craniofacial and gastrointestinal systems. At least at least 5 of the patients affected had features in three component organs so can be considered a VACTERL association. Wbp11 heterozygous null mice had vertebral and renal anomalies.
Sources: Literature
Paediatric disorders - additional genes v1.82 OTUD5 Arina Puzriakova Classified gene: OTUD5 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.82 OTUD5 Arina Puzriakova Added comment: Comment on list classification: This panel is relevant in view of the multiple congenital malformations associated with OTUD5 variants and therefore this gene may be promoted to Green at the next major review - at least 8 unrelated families reported with distinct hemizygous variants (PMIDs: 33131077 and 33523931).
Paediatric disorders - additional genes v1.82 OTUD5 Arina Puzriakova Gene: otud5 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.81 OTUD5 Arina Puzriakova gene: OTUD5 was added
gene: OTUD5 was added to Paediatric disorders - additional genes. Sources: Expert Review
Q2_21_rating tags were added to gene: OTUD5.
Mode of inheritance for gene: OTUD5 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: OTUD5 were set to 33131077; 33523931
Phenotypes for gene: OTUD5 were set to Multiple congenital anomalies-neurodevelopmental syndrome, X-linked, OMIM:301056
Review for gene: OTUD5 was set to GREEN
Added comment: OTUD5 is associated with a relevant phenotype in OMIM but not yet in Gene2Phenotype.

- PMID: 33131077 (2021) - 13 male patients from a single family with three generations affected. Patients presented prenatally or during the neonatal period with IUGR, ventriculomegaly, hydrocephalus, hypotonia, congenital heart defects, hypospadias, and severe neurodevelopmental delay. The disease is typically fatal during infancy, mainly due to sepsis (pneumonias). Female carriers are asymptomatic. WGS in four individuals identified a unique candidate variant in the OTUD5 gene (NM_017602.3:c.598G > A, p.Glu200Lys). The variant cosegregated with the disease in 10 tested individuals.

- PMID: 33523931 (2021) - Another 10 individuals from 7 families reported. Key features include poor growth, global developmental delay with impaired intellectual development, and variable abnormalities of the cardiac, skeletal, and genitourinary systems. Most affected individuals also have hypotonia and dysmorphic craniofacial features. Brain imaging typically shows enlarged ventricles and thin corpus callosum; some have microcephaly, whereas others have hydrocephalus. The severity of the disorder is highly variable, ranging from death in early infancy to survival into the second or third decade.
Sources: Expert Review
Paediatric disorders - additional genes v1.80 HYAL2 Eleanor Williams Classified gene: HYAL2 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.80 HYAL2 Eleanor Williams Added comment: Comment on list classification: After consultation with the Genomics England clinical team the recommendation is that this gene be rated green based on two unrelated families both which contain individuals with a cardiac phenotype, and a mouse model in which the cardiac phenotype is also noted.
Paediatric disorders - additional genes v1.80 HYAL2 Eleanor Williams Gene: hyal2 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.79 HYAL2 Eleanor Williams Tag for-review tag was added to gene: HYAL2.
Paediatric disorders - additional genes v1.79 MYOCD Arina Puzriakova Phenotypes for gene: MYOCD were changed from Megabladder, congenital 618719 to Megabladder, congenital, OMIM:618719; Megabladder, congenital, MONDO:0032879
Paediatric disorders - additional genes v1.78 RINT1 Eleanor Williams Classified gene: RINT1 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.78 RINT1 Eleanor Williams Added comment: Comment on list classification: Promoting this gene from red to amber, but with a recommendation for green rating following GMS review. Liver failure could lead to paediatric ITU admission and so thought appropriate for this panel.
Paediatric disorders - additional genes v1.78 RINT1 Eleanor Williams Gene: rint1 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.77 RINT1 Eleanor Williams Tag for-review tag was added to gene: RINT1.
Paediatric disorders - additional genes v1.77 RINT1 Eleanor Williams gene: RINT1 was added
gene: RINT1 was added to Paediatric disorders - additional genes. Sources: Literature
Mode of inheritance for gene: RINT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RINT1 were set to 31204009
Phenotypes for gene: RINT1 were set to Infantile liver failure syndrome 3 OMIM:618641; infantile liver failure syndrome 3 MONDO:0032844
Review for gene: RINT1 was set to GREEN
Added comment: Associated with Infantile liver failure syndrome 3 #618641 (AR) in OMIM. Probable association with Infantile-Onset Recurrent Acute Liver Failure and Skeletal Abnormalities in Gene2Phenotype.

PMID:31204009 - Cousin et al 2019 - describe 3 unrelated children with recurrent acute liver failure (RALF) and skeletal abnormalities who were found by WES to have compound heterozygous alterations in RINT1. All had splice alterations at the same position (c.1333+1G>A or G>T) together with a missense (p.Ala368Thr or p.Leu370Pro) or in-frame deletion (p.Val618_Lys619del). One variant was inherited from each parent. 2 of the 3 children had short stature. Imaging showed that they had abnormalities affecting the vertebrae and pelvis. Studies on patient dermal fibroblasts showed that the splice-variant results in skipping of exon 9 leading to an out-of-frame product and nonsense-mediated transcript decay and that there was decreased RINT1 protein levels, abnormal Golgi morphology, and impaired autophagic flux compared to control fibroblasts.
Sources: Literature
Paediatric disorders - additional genes v1.76 HYAL2 Eleanor Williams Classified gene: HYAL2 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.76 HYAL2 Eleanor Williams Gene: hyal2 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.75 HYAL2 Eleanor Williams Classified gene: HYAL2 as Red List (low evidence)
Paediatric disorders - additional genes v1.75 HYAL2 Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber. Checking with Genomics England clinical team as to whether a green rating would be appropriate.
Paediatric disorders - additional genes v1.75 HYAL2 Eleanor Williams Gene: hyal2 has been classified as Red List (Low Evidence).
Paediatric disorders - additional genes v1.74 HYAL2 Eleanor Williams gene: HYAL2 was added
gene: HYAL2 was added to Paediatric disorders - additional genes. Sources: Literature
Mode of inheritance for gene: HYAL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HYAL2 were set to 28081210; 23172227; 26515055
Phenotypes for gene: HYAL2 were set to cor triatriatum; congenital cardiac malformations
Review for gene: HYAL2 was set to AMBER
Added comment: PMID: 28081210 (Muggenthaler et al 2017) report 2 unrelated consanguineous extended families (Amish and Arab) who have an orofacial clefting phenotype with cardiac anomalies are also reported.

In pedigree 1 (Amish) 5/5 analysed individuals had cleft lip and palate. 3/5 had congenital cardiac malformations including left cor triatriatum and dilated coronary sinus consistent with persistent left superior vena cava. All had a homzogyous c.443A>G, p.K148R variant which segregated with the disorder in the pedigree. It was found in a heterozygous state at a frequency of 0.013 in the Amish population, but was not found in 1000 Genomes or ExAC databases.

In pedigree 2 (Arab) 1/2 analysed individuals had cleft lip and palate and 1/2 had an abnormal mitral valve with accessory tissue. Both were found to have a homozygous c.749C>T; p.P250L variant following whole genome SNP mapping. This variant was found in 2 individuals in the ExAC database in heterozygous state. Transient expression of the patient variants in mouse embryonic fibroblasts showed a large decrease in protein levels compared to wild type.

They report that valvular thickening and atrial dilatation are found in all Hyal2-/- mice (PMID: 23172227) and that Cor triatriatum sinister has been detected in 50% of Hyal2-/- mice (PMID: 26515055).
Sources: Literature
Paediatric disorders - additional genes v1.73 TSPYL1 Eleanor Williams Classified gene: TSPYL1 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.73 TSPYL1 Eleanor Williams Added comment: Comment on list classification: Promoting from red to amber, but with a green recommendation for GMS review. 3 cases reported.
Paediatric disorders - additional genes v1.73 TSPYL1 Eleanor Williams Gene: tspyl1 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.72 TSPYL1 Eleanor Williams Tag for-review tag was added to gene: TSPYL1.
Paediatric disorders - additional genes v1.72 TSPYL1 Eleanor Williams changed review comment from: Associated with Sudden infant death with dysgenesis of the testes syndrome #608800 (AR) in OMIM.

3 independent cases with biallelic variants in TSPYL1 in patients with Sudden Infant Death with Dysgenesis of the Testes syndrome reported.

PMID: 32885560 - Slater et al 2020 - report a Hispanic, phenotypically female infant with poor feeding and abnormal motor movements noted at birth. Mild T-cell lymphopenia, absent uterus and adnexal structures, with no gonads visible and intractable epilepsy are also reported. The patient died of respiratory failure at 8 months of age. Exome sequencing revealed homozygosity for a frameshift variant in TSPYL1 (c.725_726delTG, p.Val242GlufsTer52). The variant has a frequency of 0.002% in gnomAD but has not been reported in the homozygous state.

PMID: 33075815 - Buyse et al 2020 - report 3 affected siblings from a consanguineous Turkish family. The phenotype was characterized by visceroautonomic dysfunction, severe postnatal progressive neurological abnormalities, visual impairment, testicular dysgenesis in males and sudden death at infant age. WES analysis found a homozygous frameshift variant p.Val242GlufsTer52 in TSPYL1 in the affected siblings. The variant is found in gnomAD at a MAF of 0.0021%, but no homozygous individuals are reported. The parents and one unaffected sibling were heterozygous for the variant. The truncated protein was retained in the Golgi in patient fibroblasts whereas in control fibroblasts the full length protein was found in the nucleus. Patient cells also showed prolonged S and G2 phases with reduced cellular proliferation rates. Tspyl1 depleted zebrafish showed a similar phenotype with early lethality, defects in neurogenesis and cardiac dilation.

PMID: 15273283 - Puffenberger et al 2004 - report 21 individuals from a large Old Order Amish kinship with a phenotype of sudden infant death (from cardiac and respiratory arrest) with dysgenesis of the testes in males. A homozygous frameshift mutation c.457dupG (p.Glu153Glyfs*17) was detected after autozygosity scanning and sequencing of the the TSPYL (now known as TSPYL1) gene. All parents were heterozygous for the mutation. Functional experiments showed that there was a loss of nuclear localization of truncated TSPYL

Two reports where SIDS cases were screened for TSPYL1 variants but only heterozygous variants were found:

PMID: 25449952 - Schubert et al 2015 - screened TSPYL1 in 165 SIDS cases with mostly Swiss ethnic origin, and 163 German control adults. 8 known polymorphisms were detected, 3 affected individuals were found to have rare heterozygous missense variants (1 x c.106C>G (p.Leu36Val), 2 x c.1098C>A, p.Phe366Leu). The p.Phe366Leu variants was also found in a control individual. 2 silent rare variants were also found (1 case, 1 control).

PMID: 16418600 - Hering et al 2006 - screen TSPYL1 in 126 SIDS cases and 261 controls. Found one female one female patient with a heterozygous p.F366L amino acid polymorphism which was not found in the controls. Concluded that the genetic analysis of TSPYL1 was of limited significance in the differential diagnosis of SIDS without dysgenesis of the testes.

Reports where male infertility cases were screened for TSPYL1 variants:

PMID: 19463995 - Vinci et al 2009 - screened 100 individuals with anomalies of testicular development or function for mutations in the TSPYL1 gene. 2 heterozygous variants reported. One in a 46,XY female with complete gonadal dysgenesis (p.K320R in the conserved NAP domain) and a 46,XY male with idiopathic azoospermia (p.R89H).

PMID: 22137496 - Javaher et al 2012 - screen 104 infertile men for variants in TSPYL1. 2 potentially pathogenic heterozygous variants identified. 1 with azoospermia had a c.419C>G (p.Ser140Cys) variant and 1 with OAT syndrome had the rare c.1098C>A (p.Phe366Leu). However, 1 fertile man was also found to be heterozygous for the rare variant c.487G>A (p.Val163Ile). The authors concluded that TSPYL1 variants did not play a major role in idiopathic male infertility and would not recommend inclusion in diagnostic screening.
Sources: Literature; to: Associated with Sudden infant death with dysgenesis of the testes syndrome #608800 (AR) in OMIM.

3 independent cases with biallelic variants in TSPYL1 in patients with Sudden Infant Death with Dysgenesis of the Testes syndrome reported.

PMID: 32885560 - Slater et al 2020 - report a Hispanic, phenotypically female infant with poor feeding and abnormal motor movements noted at birth. Mild T-cell lymphopenia, absent uterus and adnexal structures, with no gonads visible and intractable epilepsy are also reported. The patient died of respiratory failure at 8 months of age. Exome sequencing revealed homozygosity for a frameshift variant in TSPYL1 (c.725_726delTG, p.Val242GlufsTer52). The variant has a frequency of 0.002% in gnomAD but has not been reported in the homozygous state.

PMID: 33075815 - Buyse et al 2020 - report 3 affected siblings from a consanguineous Turkish family. The phenotype was characterized by visceroautonomic dysfunction, severe postnatal progressive neurological abnormalities, visual impairment, testicular dysgenesis in males and sudden death at infant age. WES analysis found a homozygous frameshift variant p.Val242GlufsTer52 in TSPYL1 in the affected siblings. The variant is found in gnomAD at a MAF of 0.0021%, but no homozygous individuals are reported. The parents and one unaffected sibling were heterozygous for the variant. The truncated protein was retained in the Golgi in patient fibroblasts whereas in control fibroblasts the full length protein was found in the nucleus. Patient cells also showed prolonged S and G2 phases with reduced cellular proliferation rates. Tspyl1 depleted zebrafish showed a similar phenotype with early lethality, defects in neurogenesis and cardiac dilation.

PMID: 15273283 - Puffenberger et al 2004 - report 21 individuals from a large Old Order Amish kinship with a phenotype of sudden infant death (from cardiac and respiratory arrest) with dysgenesis of the testes in males. A homozygous frameshift mutation c.457dupG (p.Glu153Glyfs*17) was detected after autozygosity scanning and sequencing of the the TSPYL (now known as TSPYL1) gene. All parents were heterozygous for the mutation. Functional experiments showed that there was a loss of nuclear localization of truncated TSPYL

Two reports where SIDS cases were screened for TSPYL1 variants but only heterozygous variants were found:

PMID: 25449952 - Schubert et al 2015 - screened TSPYL1 in 165 SIDS cases with mostly Swiss ethnic origin, and 163 German control adults. 8 known polymorphisms were detected, 3 affected individuals were found to have rare heterozygous missense variants (1 x c.106C>G (p.Leu36Val), 2 x c.1098C>A, p.Phe366Leu). The p.Phe366Leu variants was also found in a control individual. 2 silent rare variants were also found (1 case, 1 control).

PMID: 16418600 - Hering et al 2006 - screen TSPYL1 in 126 SIDS cases and 261 controls. Found one female one female patient with a heterozygous p.F366L amino acid polymorphism which was not found in the controls. Concluded that the genetic analysis of TSPYL1 was of limited significance in the differential diagnosis of SIDS without dysgenesis of the testes.
Paediatric disorders - additional genes v1.72 TSPYL1 Eleanor Williams gene: TSPYL1 was added
gene: TSPYL1 was added to Paediatric disorders - additional genes. Sources: Literature
Mode of inheritance for gene: TSPYL1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TSPYL1 were set to Sudden infant death with dysgenesis of the testes syndrome OMIM:608800; sudden infant death-dysgenesis of the testes syndrome MONDO:0012124
Review for gene: TSPYL1 was set to GREEN
Added comment: Associated with Sudden infant death with dysgenesis of the testes syndrome #608800 (AR) in OMIM.

3 independent cases with biallelic variants in TSPYL1 in patients with Sudden Infant Death with Dysgenesis of the Testes syndrome reported.

PMID: 32885560 - Slater et al 2020 - report a Hispanic, phenotypically female infant with poor feeding and abnormal motor movements noted at birth. Mild T-cell lymphopenia, absent uterus and adnexal structures, with no gonads visible and intractable epilepsy are also reported. The patient died of respiratory failure at 8 months of age. Exome sequencing revealed homozygosity for a frameshift variant in TSPYL1 (c.725_726delTG, p.Val242GlufsTer52). The variant has a frequency of 0.002% in gnomAD but has not been reported in the homozygous state.

PMID: 33075815 - Buyse et al 2020 - report 3 affected siblings from a consanguineous Turkish family. The phenotype was characterized by visceroautonomic dysfunction, severe postnatal progressive neurological abnormalities, visual impairment, testicular dysgenesis in males and sudden death at infant age. WES analysis found a homozygous frameshift variant p.Val242GlufsTer52 in TSPYL1 in the affected siblings. The variant is found in gnomAD at a MAF of 0.0021%, but no homozygous individuals are reported. The parents and one unaffected sibling were heterozygous for the variant. The truncated protein was retained in the Golgi in patient fibroblasts whereas in control fibroblasts the full length protein was found in the nucleus. Patient cells also showed prolonged S and G2 phases with reduced cellular proliferation rates. Tspyl1 depleted zebrafish showed a similar phenotype with early lethality, defects in neurogenesis and cardiac dilation.

PMID: 15273283 - Puffenberger et al 2004 - report 21 individuals from a large Old Order Amish kinship with a phenotype of sudden infant death (from cardiac and respiratory arrest) with dysgenesis of the testes in males. A homozygous frameshift mutation c.457dupG (p.Glu153Glyfs*17) was detected after autozygosity scanning and sequencing of the the TSPYL (now known as TSPYL1) gene. All parents were heterozygous for the mutation. Functional experiments showed that there was a loss of nuclear localization of truncated TSPYL

Two reports where SIDS cases were screened for TSPYL1 variants but only heterozygous variants were found:

PMID: 25449952 - Schubert et al 2015 - screened TSPYL1 in 165 SIDS cases with mostly Swiss ethnic origin, and 163 German control adults. 8 known polymorphisms were detected, 3 affected individuals were found to have rare heterozygous missense variants (1 x c.106C>G (p.Leu36Val), 2 x c.1098C>A, p.Phe366Leu). The p.Phe366Leu variants was also found in a control individual. 2 silent rare variants were also found (1 case, 1 control).

PMID: 16418600 - Hering et al 2006 - screen TSPYL1 in 126 SIDS cases and 261 controls. Found one female one female patient with a heterozygous p.F366L amino acid polymorphism which was not found in the controls. Concluded that the genetic analysis of TSPYL1 was of limited significance in the differential diagnosis of SIDS without dysgenesis of the testes.

Reports where male infertility cases were screened for TSPYL1 variants:

PMID: 19463995 - Vinci et al 2009 - screened 100 individuals with anomalies of testicular development or function for mutations in the TSPYL1 gene. 2 heterozygous variants reported. One in a 46,XY female with complete gonadal dysgenesis (p.K320R in the conserved NAP domain) and a 46,XY male with idiopathic azoospermia (p.R89H).

PMID: 22137496 - Javaher et al 2012 - screen 104 infertile men for variants in TSPYL1. 2 potentially pathogenic heterozygous variants identified. 1 with azoospermia had a c.419C>G (p.Ser140Cys) variant and 1 with OAT syndrome had the rare c.1098C>A (p.Phe366Leu). However, 1 fertile man was also found to be heterozygous for the rare variant c.487G>A (p.Val163Ile). The authors concluded that TSPYL1 variants did not play a major role in idiopathic male infertility and would not recommend inclusion in diagnostic screening.
Sources: Literature
Paediatric disorders - additional genes v1.71 VIM Eleanor Williams gene: VIM was added
gene: VIM was added to Paediatric disorders - additional genes. Sources: Literature
Mode of inheritance for gene: VIM was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: VIM were set to 32066935
Phenotypes for gene: VIM were set to lipodystrophy HP:0009125; Craniofacial dysostosis HP:0004439; Thoracic scoliosis HP:0002943; amyotrophy
Review for gene: VIM was set to RED
Added comment: Previously variants in this gene have been associated with cataracts (PMID: 26694549, 19126778). Cogne et al 2020 (PMID: 32066935) - report a de novo heterozygous variant in VIM (c.1160 T > C; p.(Leu387Pro)) causing a syndromic disorder affecting craniofacial development, peripheral nervous system, and adipose and ectodermal tissues in a 39 year old male. The variant was identified by WES. Both parents lacked the variant. Expression of human vimentin p.(Leu387Pro) in zebrafish resulted in a phenotype of perturbed body fat distribution, and craniofacial and peripheral nervous system development. Functional studies using patient-derived and transfected cells showed that the variant affects vimentin turnover and its ability to form filaments in the absence of wild-type vimentin.

Added gene to this panel on advice from Genomics England Clinical team.
Sources: Literature
Paediatric disorders - additional genes v1.70 NHLRC2 Eleanor Williams Classified gene: NHLRC2 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.70 NHLRC2 Eleanor Williams Added comment: Comment on list classification: Changing the rating of this gene from red to amber, but with a green rating recommendation for GMS review. 3 cases reported, plus mouse and zebrafish models and functional data from patient fibroblasts.
Paediatric disorders - additional genes v1.70 NHLRC2 Eleanor Williams Gene: nhlrc2 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.69 NHLRC2 Eleanor Williams gene: NHLRC2 was added
gene: NHLRC2 was added to Paediatric disorders - additional genes. Sources: Literature
Mode of inheritance for gene: NHLRC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NHLRC2 were set to 29423877; 32435055
Phenotypes for gene: NHLRC2 were set to FINCA syndrome OMIM:618278
Review for gene: NHLRC2 was set to GREEN
Added comment: PMID: 29423877 Uusimaa et al 2018 - report 3 patients from 2 unrelated non-consanguineous Finnish families in which the children were born asymptomatic but by 2 months of age they had developed a progressive multi-organ disorder. The main clinical features included progressive cerebropulmonary symptoms, malabsorption, progressive growth failure, recurrent infections, chronic haemolytic anaemia and transient liver dysfunction. All three patients were found using WES to be compound heterozygous for NM_198514:c.442G>T, p.Asp148Tyr and c.601_602delAG, p.Arg201GlyfsTer6. Segregation data for both families is provided. The family history of the two families, traced back 7–9 generations, showed that they did not have common ancestors. Both variants are rare in both Finnish (Sequencing Initiative Suomi - 0.003 and 0.0001 respectively) and non-Finnish populations (Exac). Patient fibroblasts expressed only mRNA with the c.442G>T missense variant, and at low levels. Development of Nhlrc2 null mice stalled before the morula stage. Morpholino knockdown of nhlrc2 in zebrafish embryos showed that nhlrc2 has a role in cellular integrity of the central nervous system during development.

PMID: 32435055 - Brodsky et al 2020 - report a 2 year old Ukranian patient with FINCA syndrome who was found by WES to have compound heterozygous variants in NHLRC2 (c.442T>G, p.D148Y and c.428C>A, p.H143P). The c.428C>A variant is not found in the gnomAD database. Each parent was a carrier for one of the variants.
Sources: Literature
Paediatric disorders - additional genes v1.68 MYH7 Arina Puzriakova Phenotypes for gene: MYH7 were changed from Cardiomyopathy, dilated, 1S; Left ventricular noncompaction 5; Cardiomyopathy, hypertrophic, 1; Myopathy, myosin storage, autosomal recessive; Myopathy, myosin storage, autosomal dominant; Scapuloperoneal syndrome, myopathic type; Laing distal myopathy to Laing distal myopathy, OMIM:160500; Laing early-onset distal myopathy, MONDO:0008050; Scapuloperoneal syndrome, myopathic type, OMIM:181430; MYH7-related late-onset scapuloperoneal muscular dystrophy, MONDO:0008409; Cardiomyopathy, hypertrophic, 1, OMIM:192600; Hypertrophic cardiomyopathy 1, MONDO:0008647; Cardiomyopathy, dilated, 1S, OMIM:613426; Dilated cardiomyopathy 1S, MONDO:0013262; Myopathy, myosin storage, autosomal dominant, OMIM:608358; Myopathy, myosin storage, autosomal dominant, MONDO:0012018; Left ventricular noncompaction 5, OMIM:613426
Paediatric disorders - additional genes v1.67 CDH2 Arina Puzriakova Classified gene: CDH2 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.67 CDH2 Arina Puzriakova Added comment: Comment on list classification: Gene added following discussion with Helen Brittain (Genomics England Clinical Team) who indicated this panel is relevant in view of the multiple congenital malformations associated with CDH2 variants.

Tagged 'for-review' as there is sufficient evidence to rate this gene Green at the next GMS panel update.
Paediatric disorders - additional genes v1.67 CDH2 Arina Puzriakova Gene: cdh2 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.66 CDH2 Arina Puzriakova gene: CDH2 was added
gene: CDH2 was added to Paediatric disorders - additional genes. Sources: Literature
for-review tags were added to gene: CDH2.
Mode of inheritance for gene: CDH2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CDH2 were set to 31585109; 31650526
Phenotypes for gene: CDH2 were set to Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, OMIM:618929; Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MONDO:0030065
Review for gene: CDH2 was set to GREEN
Added comment: Associated with relevant phenotype in OMIM, and is a 'probable' gene for 'Syndromic Neurodevelopmental Disorder with Corpus Collosum, Axon, Cardiac, Ocular, and Genital Defects' in Gene2Phenotype.

2 papers (PMID: 31585109 and 31650526) describing 13 unrelated individuals with a neurodevelopmental disorder and variants in the CDH2 gene. Clinical features include GDD/ID (10/12), brain malformations - particularly agenesis of corpus callosum (11/13), cardiovascular abnormalities (9/13), and various eye abnormalities (11/13).

Cdh2 knockout in mice is embryonically lethal. Conditional inactivation of Cdh2 in the cerebral cortex leads to cortical disorganisation and CCA similar to the human phenotypes (PMIDs: 9015265, 17222817).
Sources: Literature
Paediatric disorders - additional genes v1.65 PIGQ Sarah Leigh Classified gene: PIGQ as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.65 PIGQ Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Paediatric disorders - additional genes v1.65 PIGQ Sarah Leigh Gene: pigq has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.64 PIGQ Sarah Leigh commented on gene: PIGQ: Comments from Konstantinos Varvagiannis
Homozygous or compound heterozygous mutations in PIGQ cause Epileptic encephalopathy, early infantile, 77 (MIM #618548). Johnstone et al (2020 - PMID: 32588908) describe the phenotype of 7 children (from 6 families) with biallelic PIGQ pathogenic variants. The authors also review the phenotype of 3 subjects previously reported in the literature (by Martin et al, Alazami et al, Starr et al - respective PMIDs: 24463883, 25558065, 31148362). Affected individuals displayed severe to profound global DD/ID and seizures with onset in the first year of life. There were variable other features incl. - among others - genitourinary, cardiac, skeletal, ophthalmological anomalies, gastrointestinal issues. Within the cohort there was significant morbidity/mortality. PIGQ encodes phosphatidylinositol glycan anchor biosynthesis class Q protein, playing a role (early) in the biosynthesis of the GPI-anchor. Several genes in the GPI biosynthesis pathway cause multi-system disease with DD/ID and seizures. Flow cytometry has been used in individuals with PIGQ-related disorder. Serum ALP was elevated in some (4) although - as the authors comment - elevations are more typical in disorders affecting later steps of GPI biosynthesis. More than 10 variants have been reported to date (missense / pLoF). Overall PIGQ can be considered for green rating in both ID and epilepsy gene panels.
Paediatric disorders - additional genes v1.64 PIGQ Sarah Leigh Added comment: Comment on phenotypes: According to Joanna Peas-Welch (OMIM), Multiple congenital anomalies-hypotonia-seizures syndrome-4 (MCAHS4) will replace Epileptic encephalopathy, early infantile, 77, OMIM:618548 as the name for this phenotype (12/11/2020).
Paediatric disorders - additional genes v1.64 PIGQ Sarah Leigh Phenotypes for gene: PIGQ were changed from Multiple congenital anomalies-hypotonia-seizures syndrome-4 OMIM:618548 to Multiple congenital anomalies-hypotonia-seizures syndrome-4 OMIM:618548
Paediatric disorders - additional genes v1.63 PIGQ Sarah Leigh gene: PIGQ was added
gene: PIGQ was added to Paediatric disorders - additional genes. Sources: Literature
for-review tags were added to gene: PIGQ.
Mode of inheritance for gene: PIGQ was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGQ were set to 32588908; 24463883; 25558065; 31148362
Phenotypes for gene: PIGQ were set to Multiple congenital anomalies-hypotonia-seizures syndrome-4 OMIM:618548
Review for gene: PIGQ was set to GREEN
Added comment: Associated with relevant phenotype in OMIM and as possible Gen2Phen gene for severe early onset epilepsy. At least 11 variants reported in seven unrelated cases of multiple congenital anomalies-hypotonia-seizures syndrome-4 (MCAHS4)(Epileptic encephalopathy, early infantile, 77 618548)(OMIM:618548).
Sources: Literature
Paediatric disorders - additional genes v1.62 STN1 Sarah Leigh Classified gene: STN1 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.62 STN1 Sarah Leigh Added comment: Comment on list classification: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least four variants reported in three unrelated cases, together with a supportive zebrafish model and other functional studies.

There is enough evidence for this gene to be rated GREEN at the next major review.
Paediatric disorders - additional genes v1.62 STN1 Sarah Leigh Gene: stn1 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.61 STN1 Sarah Leigh gene: STN1 was added
gene: STN1 was added to Paediatric disorders - additional genes. Sources: Literature
for-review tags were added to gene: STN1.
Mode of inheritance for gene: STN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STN1 were set to 27432940; 32627942
Phenotypes for gene: STN1 were set to Cerebroretinal microangiopathy with calcifications and cysts 2 OMIM:617341
Review for gene: STN1 was set to GREEN
Added comment: Comments from Zornitza Stark (Australian Genomics) Three individuals from unrelated families described with a multisystem disorder characterized by premature aging, pancytopaenia, hypocellular bone marrow, osteopenia, liver fibrosis, and vascular telangiectasia resulting in gastrointestinal bleeding, as well as intracranial calcifications and leukodystrophy, resulting in spasticity, ataxia, or dystonia. Gene belongs on multiple panels.
Sources: Literature
Paediatric disorders - additional genes v1.60 ACTG2 Arina Puzriakova Classified gene: ACTG2 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.60 ACTG2 Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Paediatric disorders - additional genes v1.60 ACTG2 Arina Puzriakova Gene: actg2 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.59 GREB1L Arina Puzriakova Classified gene: GREB1L as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.59 GREB1L Arina Puzriakova Added comment: Comment on list classification: Changed rating from Green to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update (added 'for-review' tag).
Paediatric disorders - additional genes v1.59 GREB1L Arina Puzriakova Gene: greb1l has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.58 GATA3 Arina Puzriakova Classified gene: GATA3 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.58 GATA3 Arina Puzriakova Added comment: Comment on list classification: Changed rating to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update.
Paediatric disorders - additional genes v1.58 GATA3 Arina Puzriakova Gene: gata3 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.57 CHRNA3 Arina Puzriakova Classified gene: CHRNA3 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.57 CHRNA3 Arina Puzriakova Added comment: Comment on list classification: Changed rating to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update.
Paediatric disorders - additional genes v1.57 CHRNA3 Arina Puzriakova Gene: chrna3 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.56 ANOS1 Arina Puzriakova Classified gene: ANOS1 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.56 ANOS1 Arina Puzriakova Added comment: Comment on list classification: Changed rating to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update.
Paediatric disorders - additional genes v1.56 ANOS1 Arina Puzriakova Gene: anos1 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.55 NADSYN1 Sarah Leigh Classified gene: NADSYN1 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.55 NADSYN1 Sarah Leigh Gene: nadsyn1 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.54 NADSYN1 Sarah Leigh Tag for-review tag was added to gene: NADSYN1.
Paediatric disorders - additional genes v1.54 NADSYN1 Sarah Leigh gene: NADSYN1 was added
gene: NADSYN1 was added to Paediatric disorders - additional genes. Sources: Expert list,Literature
Mode of inheritance for gene: NADSYN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NADSYN1 were set to 31883644
Phenotypes for gene: NADSYN1 were set to Vertebral, cardiac, renal, and limb defects syndrome 3 618845
Review for gene: NADSYN1 was set to AMBER
Added comment: Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 6 variants reported in at least 4 families, together with supportive functional studies (PMID 31883644).
Sources: Expert list, Literature
Paediatric disorders - additional genes v1.53 MYOCD Sarah Leigh Deleted their comment
Paediatric disorders - additional genes v1.53 MYOCD Sarah Leigh Classified gene: MYOCD as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.53 MYOCD Sarah Leigh Added comment: Comment on list classification: Chirag Patel (Genetic Health Queensland)(16 Jan 2020) review on CAKUT panel: Four unrelated families. Mono allelic disease in males (megabladder), bi-allelic disease in males and females (megabladder and congenital heart disease). Cosegregation of MYOCD variants with the phenotype in 4 unrelated families by in vitro transactivation studies in which pathogenic variants resulted in abrogated SM gene expression and by the finding of megabladder in 2 distinct mouse models with reduced Myocd activity.
Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 4 variants reported in at least 4 unrelated cases, together with a supportive loss of function mouse model. PMID 31513549 concludes "that monoallelic loss-of-function variants in MYOCD cause congenital megabladder in males and that biallelic variants are associated with disease manifest in females that also involves the cardiovascular system".
Paediatric disorders - additional genes v1.53 MYOCD Sarah Leigh Gene: myocd has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.53 MYOCD Sarah Leigh Classified gene: MYOCD as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.53 MYOCD Sarah Leigh Added comment: Comment on list classification: Chirag Patel (Genetic Health Queensland)(16 Jan 2020) review on CAKUT panel: Four unrelated families. Mono allelic disease in males (megabladder), bi-allelic disease in males and females (megabladder and congenital heart disease). Cosegregation of MYOCD variants with the phenotype in 4 unrelated families by in vitro transactivation studies in which pathogenic variants resulted in abrogated SM gene expression and by the finding of megabladder in 2 distinct mouse models with reduced Myocd activity.
Associated with relevant phenotype in OMIM and as probable Gen2Phen gene. At least 4 variants reported in at least 4 unrelated cases, together with a supportive loss of function mouse model. PMID 31513549 concludes "that monoallelic loss-of-function variants in MYOCD cause congenital megabladder in males and that biallelic variants are associated with disease manifest in females that also involves the cardiovascular system".
Paediatric disorders - additional genes v1.53 MYOCD Sarah Leigh Gene: myocd has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.52 MYOCD Sarah Leigh Tag for-review tag was added to gene: MYOCD.
Paediatric disorders - additional genes v1.52 MYOCD Sarah Leigh gene: MYOCD was added
gene: MYOCD was added to Paediatric disorders - additional genes. Sources: Expert Review
Mode of inheritance for gene: MYOCD was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MYOCD were set to 31513549
Phenotypes for gene: MYOCD were set to Megabladder, congenital 618719
Review for gene: MYOCD was set to AMBER
Added comment: Sources: Expert Review
Paediatric disorders - additional genes v1.51 ITGA8 Rebecca Foulger Classified gene: ITGA8 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.51 ITGA8 Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber awaiting GLH review. Additional phenotypes were reported in the fetuses and sibling (who died perinatally) from PMID:24439109 (clubbed feet, facial dysmorphism, pulmonary hypoplasia, bilateral cryptorchidism) although renal agenesis is the primary phenotype and only 2 families from one paper.
Paediatric disorders - additional genes v1.51 ITGA8 Rebecca Foulger Gene: itga8 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.50 TBX18 Rebecca Foulger Classified gene: TBX18 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.50 TBX18 Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber awaiting GLH review. Three unrelated CAKUT cases in PMID:26235987 (2015) but as Helen Brittain notes, isolated CAKUT phenotype is less relevant for the Paediatric disorders panel.
Paediatric disorders - additional genes v1.50 TBX18 Rebecca Foulger Gene: tbx18 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.49 TBX18 Rebecca Foulger Publications for gene: TBX18 were set to
Paediatric disorders - additional genes v1.49 TBX18 Rebecca Foulger Phenotypes for gene: TBX18 were changed from CAKUT to CAKUT; Congenital anomalies of kidney and urinary tract 2, 143400
Paediatric disorders - additional genes v1.48 LRIG2 Rebecca Foulger Classified gene: LRIG2 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.48 LRIG2 Rebecca Foulger Gene: lrig2 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.47 LRIG2 Rebecca Foulger Classified gene: LRIG2 as Green List (high evidence)
Paediatric disorders - additional genes v1.47 LRIG2 Rebecca Foulger Added comment: Comment on list classification: Three unrelated cases reported in PMID:23313374 (Stuart et al., 2013), although in one of the families siblings with the same homozygous variant report differing phenotypes. There is also an animal model. The facial phenotype that occurs alongside the urinary tract phenotype is an abnormal facial expression upon smiling rather than a congenital structural phenotype. Therefore have kept Amber for now awaiting clinical review.
Paediatric disorders - additional genes v1.47 LRIG2 Rebecca Foulger Gene: lrig2 has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v1.46 LRIG2 Rebecca Foulger commented on gene: LRIG2: PMID:23313374. Stuart et al., 2013 performed exome sequencing in affected siblings from a consanguineous Turkish family with urofacial syndrome. A 1bp deletion variant resulting in premature termination (Glu140AspfsTer6) was found in an 8 year old girl, but also in her 5 year old brother who exhibited the facial features but not CAKUT phenotype. The variant was found in heterozygosity in the unaffected first-cousin parents.

In a second Turkish family with urofacial syndrome, two affected sisters were homozygous for a nonsense LRIG2 variant (R709X). A third case comes from a 5year old Spanish girl compound het for a 1bp deletion (Ser697HisfsTer11) and 371bp insertion variant in LRIG2. Her unaffected parents were each heterozygous for one of the variants.

Facial phenotypes of Urofacial syndrome include grimacing on smiling.
Paediatric disorders - additional genes v1.46 LRIG2 Rebecca Foulger Publications for gene: LRIG2 were set to Stuart HM, Roberts NA, Bergu B, Daly SB, Urquhart JE, Bhaskar S, Dickerson J, Mermerkaya M, Silay MS, Lewis MA, Olondriz BO, Gener B, Beetz C, Varga RE, G lp nar O, S er E, Yal nkaya F, G c k A, Yue WW, Erdogan F, Berry A, Hanley NA, McKenzie EA, Hilton EN, Woolf AS, Newman WG. LRIG2 mutations cause urofacial syndrome. Am J Hum Genet 92:259-264, 2013.
Paediatric disorders - additional genes v1.45 LRIG2 Rebecca Foulger Phenotypes for gene: LRIG2 were changed from CAKUT; Congenital bladder disease: dyssynergic, high pressure bladder.; Urofacial syndrome to CAKUT; Urofacial syndrome 2, 615112; Congenital bladder disease: dyssynergic, high pressure bladder.; Urofacial syndrome
Paediatric disorders - additional genes v1.44 GATA3 Rebecca Foulger Classified gene: GATA3 as Green List (high evidence)
Paediatric disorders - additional genes v1.44 GATA3 Rebecca Foulger Gene: gata3 has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v1.43 GATA3 Rebecca Foulger Classified gene: GATA3 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.43 GATA3 Rebecca Foulger Added comment: Comment on list classification: Updated from Amber to Green awaiting GLH review. GATA3 HDR syndrome includes hypoparathyroidism and sensorineural deafness in addition to renal dysplasia.
Paediatric disorders - additional genes v1.43 GATA3 Rebecca Foulger Gene: gata3 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.42 GATA3 Rebecca Foulger commented on gene: GATA3: PMID:11389161. Muroya et al., 2001 report 9 Japanese families with HDR syndrome (hypoparathyroidism, sensorineural deafness, and renal dysplasia). Heterozygous gross deletions were reported by FISH in 4 families. Sequence analysis showed heterozygous novel variants in 3 families. 2 families had no GATA3 abnormalities detected.
Paediatric disorders - additional genes v1.42 GATA3 Rebecca Foulger commented on gene: GATA3: GATA3 has an Amber rating on Clefting panel v2.3.
Paediatric disorders - additional genes v1.42 REN Rebecca Foulger Classified gene: REN as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.42 REN Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber awaiting GLH review as to whether renal phenotypes are sufficient for inclusion on the Paediatric disorders panel.
Paediatric disorders - additional genes v1.42 REN Rebecca Foulger Gene: ren has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.41 REN Rebecca Foulger commented on gene: REN: PMID:31736371. He et al., performed a study to identify the potentially pathogenic gene variants that contribute to the AR renal tubular dysgenesis (RTD) in the aborted fetus. WES was performed on an aborted fetus and his parents. Compound heterozygous variants (c.963T>A, p.Y321X and c.492+1G>A splicing site mutation) were identified in the fetus, one inherited from each parent.
Paediatric disorders - additional genes v1.41 REN Rebecca Foulger Publications for gene: REN were set to
Paediatric disorders - additional genes v1.40 REN Rebecca Foulger Added comment: Comment on mode of inheritance: Hyperuricemic nephropathy, familial juvenile 2, 613092 has AD inheritance, and Renal tubular dysgenesis, 267430 has AR inheritance.
Paediatric disorders - additional genes v1.40 REN Rebecca Foulger Mode of inheritance for gene: REN was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Paediatric disorders - additional genes v1.39 REN Rebecca Foulger Phenotypes for gene: REN were changed from CAKUT; [Hyperproreninemia]; Renal Tubular Dysgenesis to CAKUT; [Hyperproreninemia]; Hyperuricemic nephropathy, familial juvenile 2, 613092; Renal tubular dysgenesis, 267430
Paediatric disorders - additional genes v1.38 GREB1L Rebecca Foulger Classified gene: GREB1L as Green List (high evidence)
Paediatric disorders - additional genes v1.38 GREB1L Rebecca Foulger Gene: greb1l has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v1.37 GREB1L Rebecca Foulger Classified gene: GREB1L as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.37 GREB1L Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green awaiting GLH review: although the predominant phenotype is renal defects, inner ear malformations are also included in the phenotypic spectrum (PMID:29955957).
Paediatric disorders - additional genes v1.37 GREB1L Rebecca Foulger Gene: greb1l has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.36 GREB1L Rebecca Foulger Phenotypes for gene: GREB1L were changed from CAKUT; Renal hypodysplasia/aplasia 3, 617805 to CAKUT; Renal hypodysplasia/aplasia 3, 617805; inner ear malformations
Paediatric disorders - additional genes v1.36 GREB1L Rebecca Foulger Publications for gene: GREB1L were set to 29100091; 29220675; 29261186
Paediatric disorders - additional genes v1.35 GREB1L Rebecca Foulger commented on gene: GREB1L: PMID:29955957. Schrauwen et al., 2018 performed trio-based WES sequencing in young unrelated subjects with inner ear malformations, and identified novel de novo LOF variants in GREB1L (Glu1410fs and Arg328*) in 2 affected subjects with absent cochleae and eighth cranial nerve malformations.
Paediatric disorders - additional genes v1.35 GREB1L Rebecca Foulger changed review comment from: PMID:29100091. Tomasi et al., 2017. WES or targeted exome sequencing of 183 unrelated familial and/or severe CAKUT-affected case subjects, including 54 fetuses with BKA, led to the identification of 16 heterozygous variants in GREB1L.
Fetal cases with bilateral kidney agenesis include p.Gln528Argfs*12 (also present in their alive brother with unilateral kidney agenesis) and splice variant c.4369−1G>C.; to: PMID:29100091. Tomasi et al., 2017. WES or targeted exome sequencing of 183 unrelated familial and/or severe CAKUT-affected case subjects, including 54 fetuses with BKA, led to the identification of 16 heterozygous variants in GREB1L. Family histories and phenotypes suggest incomplete penetrance.
Paediatric disorders - additional genes v1.35 GREB1L Rebecca Foulger Publications for gene: GREB1L were set to 29100091; 29220675
Paediatric disorders - additional genes v1.34 GREB1L Rebecca Foulger commented on gene: GREB1L: PMID:29100091. Tomasi et al., 2017. WES or targeted exome sequencing of 183 unrelated familial and/or severe CAKUT-affected case subjects, including 54 fetuses with BKA, led to the identification of 16 heterozygous variants in GREB1L.
Fetal cases with bilateral kidney agenesis include p.Gln528Argfs*12 (also present in their alive brother with unilateral kidney agenesis) and splice variant c.4369−1G>C.
Paediatric disorders - additional genes v1.34 GREB1L Rebecca Foulger commented on gene: GREB1L: PMID:29261186 (Boissel et al., 2018) performed WES in 101 fetuses or stillborns who presented prenatally with severe anomalies. In 2 cases who presented with renal agenesis, de novo variants in GREB1L were identified (p.A968V and p.S98X).
Paediatric disorders - additional genes v1.34 CHRNA3 Rebecca Foulger Phenotypes for gene: CHRNA3 were changed from CAKUT; dysautonomia; functional lower urinary tract obstruction and secondary CAKUT to CAKUT; dysautonomia; Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary CAKUT, 191800
Paediatric disorders - additional genes v1.33 CHRNA3 Rebecca Foulger Classified gene: CHRNA3 as Green List (high evidence)
Paediatric disorders - additional genes v1.33 CHRNA3 Rebecca Foulger Added comment: Comment on list classification: Updated gene from Amber to Green, awaiting GLH review. CAKUT is secondary to bladder obstruction, and therefore additional congenital defects may present (PMID:31708116).
Paediatric disorders - additional genes v1.33 CHRNA3 Rebecca Foulger Gene: chrna3 has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v1.32 CHRNA3 Rebecca Foulger changed review comment from: PMID:31708116 (Mann et al., 2019) identify 3 different biallelic variants in CHRNA2 in 5 individuals from 3 unrelated families with functional lower urinary tract obstruction and secondary CAKUT. All 3 variants impair acetylcholine signaling. The truncating variants p.Thr337Asnfs∗81 and p.Ser340∗ led to impaired plasma membrane localization of CHRNA3. The third variant is an essential splice site variant. None of the variants were present in gnomAD.; to: PMID:31708116 (Mann et al., 2019) identify 3 different biallelic variants in CHRNA3 in 5 individuals from 3 unrelated families with functional lower urinary tract obstruction and secondary CAKUT. All 3 variants impair acetylcholine signaling. The truncating variants p.Thr337Asnfs∗81 and p.Ser340∗ led to impaired plasma membrane localization of CHRNA3. The third variant is an essential splice site variant. None of the variants were present in gnomAD.
Paediatric disorders - additional genes v1.32 AGTR1 Rebecca Foulger Classified gene: AGTR1 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.32 AGTR1 Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber for now. Plenty of literature suggesting links between AGTR1 polymorphisms and disease risk for e.g. pulmonary arterial hypertension (e.g. PMID:25603901) but key congenital disorder seems to be renal dysgenesis (PMID:16116425).
Paediatric disorders - additional genes v1.32 AGTR1 Rebecca Foulger Gene: agtr1 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.31 AGTR1 Rebecca Foulger commented on gene: AGTR1: PMID:16116425. Gribouval et al. 2005 studied 9 families (11 indivs) with AR renal tubular dysgenesis, and found variants in REN, AGT, ACE or AGTR1.
Paediatric disorders - additional genes v1.31 ANOS1 Rebecca Foulger Classified gene: ANOS1 as Green List (high evidence)
Paediatric disorders - additional genes v1.31 ANOS1 Rebecca Foulger Gene: anos1 has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v1.30 ANOS1 Rebecca Foulger Classified gene: ANOS1 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.30 ANOS1 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green, awaiting GLH review. Sufficient cases to support Kallman syndrome association, which can present with phenotypes beyond renal, some of which could be detected at birth.
Paediatric disorders - additional genes v1.30 ANOS1 Rebecca Foulger Gene: anos1 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.29 ANOS1 Rebecca Foulger commented on gene: ANOS1: PMID:16423815. Trarbach et al 2005 report 12 Kallmann syndrome (KS) patients. Two ANOS1 variants (referred to as KAL-1 gene) were found in 2 KS patients (Arg191X, and del1956C leading to a premature stop codon at 617). A patient with a KAL-1 microdeletion was also reported. Renal agenesis and bimanual synkinesis were observed in these cases.
Paediatric disorders - additional genes v1.29 ANOS1 Rebecca Foulger Publications for gene: ANOS1 were set to 1518845
Paediatric disorders - additional genes v1.28 ANOS1 Rebecca Foulger Phenotypes for gene: ANOS1 were changed from CAKUT; Kallman syndrome; Hypogonadotropic hypogonadism 1 with or without anosmia (Kallmann syndrome 1) to CAKUT; Kallman syndrome; Hypogonadotropic hypogonadism 1 with or without anosmia (Kallmann syndrome 1), 308700
Paediatric disorders - additional genes v1.27 AGT Rebecca Foulger Classified gene: AGT as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.27 AGT Rebecca Foulger Added comment: Comment on list classification: Kept rating as Amber for now: renal tubulogenesis is key phenotype and therefore CAKUT may be isolated.
Paediatric disorders - additional genes v1.27 AGT Rebecca Foulger Gene: agt has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.26 ACTG2 Rebecca Foulger Classified gene: ACTG2 as Green List (high evidence)
Paediatric disorders - additional genes v1.26 ACTG2 Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green based on papers demonstrating a role in MMIHS (e.g. PMID:27481187, 25998219), thereby broadening phenotype from isolated CAKUT.
Paediatric disorders - additional genes v1.26 ACTG2 Rebecca Foulger Gene: actg2 has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v1.25 ACTG2 Rebecca Foulger changed review comment from: PMID:27481187 Moreno et al., 201. In 3 individuals with MMIHS and in 1 with chronic intestinal pseudo-obstruction (CIPO) they identified a heterozygous variant in ACTG2, one being a novel variant (c.584C>T-p.Thr195Ile).; to: PMID:27481187 Moreno et al., 2016. In 3 individuals with MMIHS and in 1 with chronic intestinal pseudo-obstruction (CIPO) they identified a heterozygous variant in ACTG2, one being a novel variant (c.584C>T-p.Thr195Ile).
Paediatric disorders - additional genes v1.25 ACTG2 Rebecca Foulger commented on gene: ACTG2: PMID:27481187 Moreno et al., 201. In 3 individuals with MMIHS and in 1 with chronic intestinal pseudo-obstruction (CIPO) they identified a heterozygous variant in ACTG2, one being a novel variant (c.584C>T-p.Thr195Ile).
Paediatric disorders - additional genes v1.25 ACTG2 Rebecca Foulger Publications for gene: ACTG2 were set to 25998219
Paediatric disorders - additional genes v1.24 ACTG2 Rebecca Foulger changed review comment from: PMID:25998219. Tuzovic et al identify a heterozygous de novo missense variant in ACTG2 (p.Arg257His) in 2 siblings with MMIHS. 2 additional missense variants in ACTG2 (p.Arg257Cys and p.Arg178His) were identified in 2 additional MMHIS patients. All patients had evidence of fetal megacystis. Additional findings included bilateral renal hydronephrosis, an enlarged fetal stomach, and transient dilated bowel loops. Note that in OMIM, MMHIS (MIM:249210) is associated with MYLK.; to: PMID:25998219. Tuzovic et al identify a heterozygous de novo missense variant in ACTG2 (p.Arg257His) in 2 siblings with MMIHS. 2 additional missense variants in ACTG2 (p.Arg257Cys and p.Arg178His) were identified in 2 additional MMIHS patients. All patients had evidence of fetal megacystis. Additional findings included bilateral renal hydronephrosis, an enlarged fetal stomach, and transient dilated bowel loops. Note that in OMIM, MMIHS (MIM:249210) is associated with MYLK.
Paediatric disorders - additional genes v1.24 ACE Rebecca Foulger Classified gene: ACE as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.24 ACE Rebecca Foulger Added comment: Comment on list classification: Key papers report renal tubular dysgenesis. In absence of additional morphological features, keep Amber awaiting GLH review.
Paediatric disorders - additional genes v1.24 ACE Rebecca Foulger Gene: ace has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.23 ACE Rebecca Foulger commented on gene: ACE: PMID:30058238 (Bhowmik et al., 2018) report a 32-week old fetus with severe early onset oligohydramnios. A similarly affected sibling was reported from a previous pregnancy. Exome sequencing revealed a homozygous 3' splice-site variant in intron 17 of ACE gene, which confirmed AR renal tubular dysgenesis. It also facilitated prenatal diagnosis in a subsequent pregnancy.
Paediatric disorders - additional genes v1.23 ACE Rebecca Foulger commented on gene: ACE: PMID:16116425. Gribouval et al. 2005 studied 9 families (11 indivs) with AR renal tubular dysgenesis, and found variants in REN, AGT, ACE or AGTR1.
Paediatric disorders - additional genes v1.23 CHRNA3 Rebecca Foulger changed review comment from: Added 'for-review' tag: Requires GLH review as to whether CAKUT phenotype is sufficient for inclusion on Paediatric disorders panel.; to: Added 'for-review' tag: Requires GLH review as to whether phenotype is sufficient for inclusion on Paediatric disorders panel.
Paediatric disorders - additional genes v1.23 CHRNA3 Rebecca Foulger Phenotypes for gene: CHRNA3 were changed from CAKUT; dysautonomia to CAKUT; dysautonomia; functional lower urinary tract obstruction and secondary CAKUT
Paediatric disorders - additional genes v1.22 CHRNA3 Rebecca Foulger commented on gene: CHRNA3: PMID:31708116 (Mann et al., 2019) identify 3 different biallelic variants in CHRNA2 in 5 individuals from 3 unrelated families with functional lower urinary tract obstruction and secondary CAKUT. All 3 variants impair acetylcholine signaling. The truncating variants p.Thr337Asnfs∗81 and p.Ser340∗ led to impaired plasma membrane localization of CHRNA3. The third variant is an essential splice site variant. None of the variants were present in gnomAD.
Paediatric disorders - additional genes v1.22 ANOS1 Rebecca Foulger changed review comment from: Added 'for-review' tag: Requires GLH review as to whether CAKUT phenotype is sufficient for inclusion on Paediatric disorders panel.; to: Added 'for-review' tag: Requires GLH review as to whether phenotype is sufficient for inclusion on Paediatric disorders panel.
Paediatric disorders - additional genes v1.22 ANOS1 Rebecca Foulger changed review comment from: Sufficient cases of variants in ANOS1 to support association with Kallmann syndrome (MIM:308700). KS phenotypes are present at birth and can include renal agenesis, and micropenis. Cases are often reported at puberty with lack of sexual development.; to: Sufficient cases of variants in ANOS1 to support association with Kallmann syndrome (MIM:308700). KS phenotypes are present at birth and can include renal agenesis, and micropenis. Cases are often reported at puberty with lack of sexual development.
Paediatric disorders - additional genes v1.22 ANOS1 Rebecca Foulger Publications for gene: ANOS1 were set to
Paediatric disorders - additional genes v1.21 ANOS1 Rebecca Foulger commented on gene: ANOS1: Sufficient cases of variants in ANOS1 to support association with Kallmann syndrome (MIM:308700). KS phenotypes are present at birth and can include renal agenesis, and micropenis. Cases are often reported at puberty with lack of sexual development.
Paediatric disorders - additional genes v1.21 AGT Rebecca Foulger commented on gene: AGT: PMID:16116425. Gribouval et al. 2005 studied 9 families (11 indivs) with AR renal tubular dysgenesis, and found variants in REN, AGT, ACE or AGTR1.
Paediatric disorders - additional genes v1.21 AGT Rebecca Foulger changed review comment from: Added to Paediatric disorders - additional genes panel, based on Green rating on CAKUT panel V1.106. Note that AGT is on V14.137 Paediatric panel already but with Red rating.; to: Added to Paediatric disorders - additional genes panel, based on Green rating on CAKUT panel V1.106. Note that AGT is on V14.137 Paediatric disorders panel already but with Red rating.
Paediatric disorders - additional genes v1.21 AGT Rebecca Foulger Phenotypes for gene: AGT were changed from CAKUT; {Hypertension, essential, susceptibility to}, 145500{Preeclampsia, susceptibility to}Renal tubular dysgenesis, 267430; Renal Tubular Dysgenesis to Renal tubular dysgenesis, 267430; CAKUT
Paediatric disorders - additional genes v1.20 AGT Rebecca Foulger Publications for gene: AGT were set to
Paediatric disorders - additional genes v1.19 ACTG2 Rebecca Foulger changed review comment from: Added 'for-review' tag: Requires GLH review as to whether CAKUT phenotype is sufficient for inclusion on Paediatric disorders panel.; to: Added 'for-review' tag: Requires GLH review for inclusion on Paediatric disorders panel: whether CAKUT phenotype presents alongside additional congenital malformations.
Paediatric disorders - additional genes v1.19 ACTG2 Rebecca Foulger commented on gene: ACTG2: PMID:25998219. Tuzovic et al identify a heterozygous de novo missense variant in ACTG2 (p.Arg257His) in 2 siblings with MMIHS. 2 additional missense variants in ACTG2 (p.Arg257Cys and p.Arg178His) were identified in 2 additional MMHIS patients. All patients had evidence of fetal megacystis. Additional findings included bilateral renal hydronephrosis, an enlarged fetal stomach, and transient dilated bowel loops. Note that in OMIM, MMHIS (MIM:249210) is associated with MYLK.
Paediatric disorders - additional genes v1.19 ACTG2 Rebecca Foulger Phenotypes for gene: ACTG2 were changed from CAKUT; Megacystis-microcolon intestinal hypoperistalsis syndrome; visceral myopathy; Berdon syndrome to CAKUT; Megacystis-microcolon intestinal hypoperistalsis syndrome; Visceral myopathy, 155310; Berdon syndrome
Paediatric disorders - additional genes v1.18 ACE Rebecca Foulger Publications for gene: ACE were set to 16116425; 22095942
Paediatric disorders - additional genes v1.17 ACE Rebecca Foulger changed review comment from: Added 'for-review' tag: Requires GLH review as to whether CAKUT phenotype is sufficient for inclusion on Paediatric disorders panel.; to: Added 'for-review' tag: Requires GLH review for inclusion on Paediatric disorders panel: whether CAKUT phenotype presents alongside additional congenital malformations.
Paediatric disorders - additional genes v1.17 ACE Rebecca Foulger Publications for gene: ACE were set to
Paediatric disorders - additional genes v1.16 TBX18 Rebecca Foulger Classified gene: TBX18 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.16 TBX18 Rebecca Foulger Gene: tbx18 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.15 REN Rebecca Foulger Classified gene: REN as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.15 REN Rebecca Foulger Gene: ren has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.14 LRIG2 Rebecca Foulger Classified gene: LRIG2 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.14 LRIG2 Rebecca Foulger Gene: lrig2 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.13 ITGA8 Rebecca Foulger Classified gene: ITGA8 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.13 ITGA8 Rebecca Foulger Gene: itga8 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.12 GREB1L Rebecca Foulger Classified gene: GREB1L as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.12 GREB1L Rebecca Foulger Gene: greb1l has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.11 GATA3 Rebecca Foulger Classified gene: GATA3 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.11 GATA3 Rebecca Foulger Gene: gata3 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.10 CHRNA3 Rebecca Foulger Classified gene: CHRNA3 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.10 CHRNA3 Rebecca Foulger Gene: chrna3 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.9 ANOS1 Rebecca Foulger Classified gene: ANOS1 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.9 ANOS1 Rebecca Foulger Gene: anos1 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.8 AGTR1 Rebecca Foulger Classified gene: AGTR1 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.8 AGTR1 Rebecca Foulger Gene: agtr1 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.7 AGT Rebecca Foulger Classified gene: AGT as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.7 AGT Rebecca Foulger Gene: agt has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.6 ACTG2 Rebecca Foulger Classified gene: ACTG2 as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.6 ACTG2 Rebecca Foulger Gene: actg2 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.5 ACE Rebecca Foulger Classified gene: ACE as Amber List (moderate evidence)
Paediatric disorders - additional genes v1.5 ACE Rebecca Foulger Gene: ace has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v1.4 TBX18 Rebecca Foulger Tag for-review tag was added to gene: TBX18.
Paediatric disorders - additional genes v1.4 TBX18 Rebecca Foulger commented on gene: TBX18: Added 'for-review' tag: Requires GLH review as to whether CAKUT phenotype is sufficient for inclusion on Paediatric disorders panel.
Paediatric disorders - additional genes v1.4 GREB1L Rebecca Foulger Tag for-review tag was added to gene: GREB1L.
Paediatric disorders - additional genes v1.4 GREB1L Rebecca Foulger commented on gene: GREB1L: Added 'for-review' tag: Requires GLH review as to whether CAKUT phenotype is sufficient for inclusion on Paediatric disorders panel.
Paediatric disorders - additional genes v1.4 REN Rebecca Foulger Tag for-review tag was added to gene: REN.
Paediatric disorders - additional genes v1.4 REN Rebecca Foulger commented on gene: REN: Added 'for-review' tag: Requires GLH review as to whether CAKUT phenotype is sufficient for inclusion on Paediatric disorders panel.
Paediatric disorders - additional genes v1.4 LRIG2 Rebecca Foulger Tag for-review tag was added to gene: LRIG2.
Paediatric disorders - additional genes v1.4 LRIG2 Rebecca Foulger commented on gene: LRIG2: Added 'for-review' tag: Requires GLH review as to whether CAKUT phenotype is sufficient for inclusion on Paediatric disorders panel.
Paediatric disorders - additional genes v1.4 ITGA8 Rebecca Foulger Tag for-review tag was added to gene: ITGA8.
Paediatric disorders - additional genes v1.4 ITGA8 Rebecca Foulger commented on gene: ITGA8: Added 'for-review' tag: Requires GLH review as to whether CAKUT phenotype is sufficient for inclusion on Paediatric disorders panel.
Paediatric disorders - additional genes v1.4 GATA3 Rebecca Foulger Tag for-review tag was added to gene: GATA3.
Paediatric disorders - additional genes v1.4 GATA3 Rebecca Foulger commented on gene: GATA3: Added 'for-review' tag: Requires GLH review as to whether CAKUT phenotype is sufficient for inclusion on Paediatric disorders panel.
Paediatric disorders - additional genes v1.4 CHRNA3 Rebecca Foulger Tag for-review tag was added to gene: CHRNA3.
Paediatric disorders - additional genes v1.4 CHRNA3 Rebecca Foulger commented on gene: CHRNA3: Added 'for-review' tag: Requires GLH review as to whether CAKUT phenotype is sufficient for inclusion on Paediatric disorders panel.
Paediatric disorders - additional genes v1.4 ANOS1 Rebecca Foulger Tag for-review tag was added to gene: ANOS1.
Paediatric disorders - additional genes v1.4 ANOS1 Rebecca Foulger commented on gene: ANOS1: Added 'for-review' tag: Requires GLH review as to whether CAKUT phenotype is sufficient for inclusion on Paediatric disorders panel.
Paediatric disorders - additional genes v1.4 AGTR1 Rebecca Foulger Tag for-review tag was added to gene: AGTR1.
Paediatric disorders - additional genes v1.4 AGTR1 Rebecca Foulger commented on gene: AGTR1: Added 'for-review' tag: Requires GLH review as to whether CAKUT phenotype is sufficient for inclusion on Paediatric disorders panel.
Paediatric disorders - additional genes v1.4 AGT Rebecca Foulger Tag for-review tag was added to gene: AGT.
Paediatric disorders - additional genes v1.4 AGT Rebecca Foulger commented on gene: AGT: Added 'for-review' tag: Requires GLH review as to whether CAKUT phenotype is sufficient for inclusion on Paediatric disorders panel.
Paediatric disorders - additional genes v1.4 ACTG2 Rebecca Foulger commented on gene: ACTG2: Added 'for-review' tag: Requires GLH review as to whether CAKUT phenotype is sufficient for inclusion on Paediatric disorders panel.
Paediatric disorders - additional genes v1.4 ACTG2 Rebecca Foulger Tag for-review tag was added to gene: ACTG2.
Paediatric disorders - additional genes v1.4 ACE Rebecca Foulger commented on gene: ACE: Added 'for-review' tag: Requires GLH review as to whether CAKUT phenotype is sufficient for inclusion on Paediatric disorders panel.
Paediatric disorders - additional genes v1.4 ACE Rebecca Foulger Tag for-review tag was added to gene: ACE.
Paediatric disorders - additional genes v1.4 AGT Rebecca Foulger commented on gene: AGT
Paediatric disorders - additional genes v1.4 TBX18 Rebecca Foulger commented on gene: TBX18
Paediatric disorders - additional genes v1.4 LRIG2 Rebecca Foulger commented on gene: LRIG2
Paediatric disorders - additional genes v1.4 ITGA8 Rebecca Foulger commented on gene: ITGA8
Paediatric disorders - additional genes v1.4 GATA3 Rebecca Foulger commented on gene: GATA3
Paediatric disorders - additional genes v1.4 REN Rebecca Foulger commented on gene: REN
Paediatric disorders - additional genes v1.4 GREB1L Rebecca Foulger commented on gene: GREB1L
Paediatric disorders - additional genes v1.4 CHRNA3 Rebecca Foulger commented on gene: CHRNA3
Paediatric disorders - additional genes v1.4 ANOS1 Rebecca Foulger commented on gene: ANOS1
Paediatric disorders - additional genes v1.4 AGTR1 Rebecca Foulger commented on gene: AGTR1
Paediatric disorders - additional genes v1.4 ACTG2 Rebecca Foulger commented on gene: ACTG2
Paediatric disorders - additional genes v1.4 ACE Rebecca Foulger commented on gene: ACE
Paediatric disorders - additional genes v1.3 AGT Rebecca Foulger gene: AGT was added
gene: AGT was added to Paediatric disorders - additional genes. Sources: Other,Expert Review Green
Mode of inheritance for gene: AGT was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: AGT were set to CAKUT; {Hypertension, essential, susceptibility to}, 145500{Preeclampsia, susceptibility to}Renal tubular dysgenesis, 267430; Renal Tubular Dysgenesis
Paediatric disorders - additional genes v1.3 TBX18 Rebecca Foulger gene: TBX18 was added
gene: TBX18 was added to Paediatric disorders - additional genes. Sources: Other,Expert Review Green
Mode of inheritance for gene: TBX18 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TBX18 were set to CAKUT
Paediatric disorders - additional genes v1.3 LRIG2 Rebecca Foulger gene: LRIG2 was added
gene: LRIG2 was added to Paediatric disorders - additional genes. Sources: Other,Expert Review Green
Mode of inheritance for gene: LRIG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRIG2 were set to Stuart HM, Roberts NA, Bergu B, Daly SB, Urquhart JE, Bhaskar S, Dickerson J, Mermerkaya M, Silay MS, Lewis MA, Olondriz BO, Gener B, Beetz C, Varga RE, G lp nar O, S er E, Yal nkaya F, G c k A, Yue WW, Erdogan F, Berry A, Hanley NA, McKenzie EA, Hilton EN, Woolf AS, Newman WG. LRIG2 mutations cause urofacial syndrome. Am J Hum Genet 92:259-264, 2013.
Phenotypes for gene: LRIG2 were set to CAKUT; Congenital bladder disease: dyssynergic, high pressure bladder.; Urofacial syndrome
Paediatric disorders - additional genes v1.3 ITGA8 Rebecca Foulger gene: ITGA8 was added
gene: ITGA8 was added to Paediatric disorders - additional genes. Sources: Other,Expert Review Green
Mode of inheritance for gene: ITGA8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ITGA8 were set to CAKUT; Renal hypodysplasia/aplasia 1, 191830
Paediatric disorders - additional genes v1.3 GATA3 Rebecca Foulger gene: GATA3 was added
gene: GATA3 was added to Paediatric disorders - additional genes. Sources: Other,Expert Review Green
Mode of inheritance for gene: GATA3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: GATA3 were set to CAKUT; Hypoparathyroidism, sensorineural deafness, and renal dysplasia, 146255; Hypoparathyroidism, Sensorineural Deafness, and Renal Disease
Paediatric disorders - additional genes v1.3 REN Rebecca Foulger gene: REN was added
gene: REN was added to Paediatric disorders - additional genes. Sources: Other,Expert Review Green
Mode of inheritance for gene: REN was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: REN were set to CAKUT; [Hyperproreninemia]; Renal Tubular Dysgenesis
Paediatric disorders - additional genes v1.3 GREB1L Rebecca Foulger gene: GREB1L was added
gene: GREB1L was added to Paediatric disorders - additional genes. Sources: Other,Expert Review Green
Mode of inheritance for gene: GREB1L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GREB1L were set to 29100091; 29220675
Phenotypes for gene: GREB1L were set to CAKUT; Renal hypodysplasia/aplasia 3, 617805
Paediatric disorders - additional genes v1.3 CHRNA3 Rebecca Foulger gene: CHRNA3 was added
gene: CHRNA3 was added to Paediatric disorders - additional genes. Sources: Other,Expert Review Green
Mode of inheritance for gene: CHRNA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHRNA3 were set to 31708116
Phenotypes for gene: CHRNA3 were set to CAKUT; dysautonomia
Paediatric disorders - additional genes v1.3 ANOS1 Rebecca Foulger gene: ANOS1 was added
gene: ANOS1 was added to Paediatric disorders - additional genes. Sources: Other,Expert Review Green
Mode of inheritance for gene: ANOS1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: ANOS1 were set to CAKUT; Kallman syndrome; Hypogonadotropic hypogonadism 1 with or without anosmia (Kallmann syndrome 1)
Paediatric disorders - additional genes v1.3 AGTR1 Rebecca Foulger gene: AGTR1 was added
gene: AGTR1 was added to Paediatric disorders - additional genes. Sources: Other,Expert Review Green
Mode of inheritance for gene: AGTR1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: AGTR1 were set to CAKUT; Hypertension, essential, 145500; Renal Tubular Dysgenesis; Renal tubular dysgenesis, 267430
Paediatric disorders - additional genes v1.3 ACTG2 Rebecca Foulger gene: ACTG2 was added
gene: ACTG2 was added to Paediatric disorders - additional genes. Sources: Other,Expert Review Green
Mode of inheritance for gene: ACTG2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ACTG2 were set to 25998219
Phenotypes for gene: ACTG2 were set to CAKUT; Megacystis-microcolon intestinal hypoperistalsis syndrome; visceral myopathy; Berdon syndrome
Paediatric disorders - additional genes v1.3 ACE Rebecca Foulger gene: ACE was added
gene: ACE was added to Paediatric disorders - additional genes. Sources: Other,Expert Review Green
Mode of inheritance for gene: ACE was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ACE were set to CAKUT; Renal Tubular Dysgenesis
Paediatric disorders - additional genes v1.2 Rebecca Foulger Panel version has been signed off
Paediatric disorders - additional genes v1.1 Rebecca Foulger Panel types changed to GMS Rare Disease; Component Of Super Panel; GMS signed-off
Paediatric disorders - additional genes v1.0 Rebecca Foulger promoted panel to version 1.0
Paediatric disorders - additional genes v0.47 Rebecca Foulger Panel types changed to GMS Rare Disease Virtual; Component Of Super Panel; GMS signed-off
Paediatric disorders - additional genes v0.46 GDF1 Rebecca Foulger Phenotypes for gene: GDF1 were changed from Right atrial isomerism (Ivemark); Congenital heart defects, multiple types, 6 to Right atrial isomerism (Ivemark), 208530; Congenital heart defects, multiple types, 6, 613854
Paediatric disorders - additional genes v0.45 GDF1 Rebecca Foulger Added comment: Comment on mode of inheritance: Updated MOI from MONOALLELIC to BOTH monoallelic and biallelic, to match suggested MOI in review, and MOI on 'Laterality disorders and isomerism' panel, version 1.0 (panel 549). GDF1 has AD inheritance for Congenital heart defects, multiple types, 6 (MIM:613854) and AR inheritance for Right atrial isomerism (Ivemark) (MIM:208530).
Paediatric disorders - additional genes v0.45 GDF1 Rebecca Foulger Mode of inheritance for gene: GDF1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Paediatric disorders - additional genes v0.44 MYH7 Rebecca Foulger Added comment: Comment on mode of inheritance: Updated MOI from MONOALLELIC to BOTH monoallelic and biallelic to match suggested MOI in review, and MOI of MYH7 on 'Cardiomyopathies - including childhood onset' panel (panel 749) version 1.0. Myopathy, myosin storage, autosomal recessive (MIM:255160) has AR inheritance in OMIM.
Paediatric disorders - additional genes v0.44 MYH7 Rebecca Foulger Mode of inheritance for gene: MYH7 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Paediatric disorders - additional genes v0.43 Rebecca Foulger Panel types changed to GMS Rare Disease Virtual; Component Of Super Panel
Paediatric disorders - additional genes v0.42 PLD1 Ellen McDonagh Classified gene: PLD1 as Amber List (moderate evidence)
Paediatric disorders - additional genes v0.42 PLD1 Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Amber, as two families have been reported (see publication).
Paediatric disorders - additional genes v0.42 PLD1 Ellen McDonagh Gene: pld1 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v0.41 GDF1 Ellen McDonagh Mode of inheritance for gene: GDF1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric disorders - additional genes v0.40 GDF1 Ellen McDonagh Classified gene: GDF1 as Green List (high evidence)
Paediatric disorders - additional genes v0.40 GDF1 Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green. This gene is Green on the Familial non syndromic congenital heart disease (panel 212, Version 1.49).
Paediatric disorders - additional genes v0.40 GDF1 Ellen McDonagh Gene: gdf1 has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v0.40 GDF1 Ellen McDonagh Classified gene: GDF1 as Green List (high evidence)
Paediatric disorders - additional genes v0.40 GDF1 Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green. This gene is Green on the Familial non syndromic congenital heart disease (panel 212, Version 1.49).
Paediatric disorders - additional genes v0.40 GDF1 Ellen McDonagh Gene: gdf1 has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v0.39 MYH7 Ellen McDonagh Added comment: Comment on mode of inheritance: Awaiting confirmation that this gene should be 'both' or monoallelic as mode of inheritance.
Paediatric disorders - additional genes v0.39 MYH7 Ellen McDonagh Mode of inheritance for gene: MYH7 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric disorders - additional genes v0.38 MYH7 Ellen McDonagh Classified gene: MYH7 as Green List (high evidence)
Paediatric disorders - additional genes v0.38 MYH7 Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green, as this gene is Green on multiple version 1+ cardio panels.
Paediatric disorders - additional genes v0.38 MYH7 Ellen McDonagh Gene: myh7 has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v0.37 CFAP53 Ellen McDonagh Marked gene: CFAP53 as ready
Paediatric disorders - additional genes v0.37 CFAP53 Ellen McDonagh Gene: cfap53 has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v0.37 CFAP53 Ellen McDonagh Classified gene: CFAP53 as Green List (high evidence)
Paediatric disorders - additional genes v0.37 CFAP53 Ellen McDonagh Added comment: Comment on list classification: This gene is Green on the Familial non syndromic congenital heart disease (panel 212 version 1.49). Promoted from Red to Green.
Paediatric disorders - additional genes v0.37 CFAP53 Ellen McDonagh Gene: cfap53 has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v0.36 ACTC1 Ellen McDonagh Classified gene: ACTC1 as Green List (high evidence)
Paediatric disorders - additional genes v0.36 ACTC1 Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green as this gene is on multiple cardio version 1+ panels.
Paediatric disorders - additional genes v0.36 ACTC1 Ellen McDonagh Gene: actc1 has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v0.35 ACTC1 Ellen McDonagh Marked gene: ACTC1 as ready
Paediatric disorders - additional genes v0.35 ACTC1 Ellen McDonagh Gene: actc1 has been classified as Red List (Low Evidence).
Paediatric disorders - additional genes v0.35 DNAH5 Ellen McDonagh reviewed gene: DNAH5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 3, with or without situs inversus ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric disorders - additional genes v0.35 CRELD1 Ellen McDonagh reviewed gene: CRELD1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Atrioventricular septal defect, partial, with heterotaxy syndrome, Atrioventricular septal defect, susceptibility to, 2; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric disorders - additional genes v0.35 ZFPM2 Ellen McDonagh reviewed gene: ZFPM2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Tetralogy of Fallot; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric disorders - additional genes v0.35 TLL1 Ellen McDonagh reviewed gene: TLL1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Atrial septal defect 6; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric disorders - additional genes v0.35 PRDM6 Ellen McDonagh reviewed gene: PRDM6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Patent ductus arteriosus 3; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric disorders - additional genes v0.35 NKX2-6 Ellen McDonagh reviewed gene: NKX2-6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Conotruncal heart malformations, Persistent truncus arteriosus; Mode of inheritance: Unknown
Paediatric disorders - additional genes v0.35 GDF1 Ellen McDonagh reviewed gene: GDF1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Congenital heart defects, multiple types, 6, Right atrial isomerism (Ivemark) ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Paediatric disorders - additional genes v0.35 FOXH1 Ellen McDonagh reviewed gene: FOXH1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: Unknown
Paediatric disorders - additional genes v0.35 DNAI1 Ellen McDonagh reviewed gene: DNAI1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 1, with or without situs inversus ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric disorders - additional genes v0.35 DNAH11 Ellen McDonagh reviewed gene: DNAH11: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Ciliary dyskinesia, primary, 7, with or without situs inversus ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric disorders - additional genes v0.35 STK4 Ellen McDonagh reviewed gene: STK4: Rating: AMBER; Mode of pathogenicity: ; Publications: 22294732, 22174160; Phenotypes: T-cell immunodeficiency, recurrent infections, autoimmunity, and cardiac malformations; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric disorders - additional genes v0.35 PLD1 Ellen McDonagh reviewed gene: PLD1: Rating: AMBER; Mode of pathogenicity: ; Publications: 27799408; Phenotypes: Cardiac valvular defect, developmental; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric disorders - additional genes v0.35 MYH7 Ellen McDonagh reviewed gene: MYH7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Cardiomyopathy, dilated, 1S, Cardiomyopathy, hypertrophic, 1, Laing distal myopathy, Left ventricular noncompaction 5, Myopathy, myosin storage, autosomal dominant, Myopathy, myosin storage, autosomal recessive, Scapuloperoneal syndrome, myopathic type ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Paediatric disorders - additional genes v0.35 GATA5 Ellen McDonagh reviewed gene: GATA5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Congenital heart defects, multiple types, 5; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Paediatric disorders - additional genes v0.35 CITED2 Ellen McDonagh reviewed gene: CITED2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Atrial septal defect 8, Ventricular septal defect 2 ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric disorders - additional genes v0.35 CFAP53 Ellen McDonagh reviewed gene: CFAP53: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Heterotaxy, visceral, 6, autosomal recessive; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric disorders - additional genes v0.35 ACTC1 Ellen McDonagh reviewed gene: ACTC1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Atrial septal defect 5, Cardiomyopathy, dilated, 1R, Cardiomyopathy, hypertrophic, 11, Left ventricular noncompaction 4; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric disorders - additional genes v0.34 DNAH5 Ellen McDonagh gene: DNAH5 was added
gene: DNAH5 was added to Paediatric disorders - additional genes. Sources: South West GLH
Mode of inheritance for gene: DNAH5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DNAH5 were set to Ciliary dyskinesia, primary, 3, with or without situs inversus
Paediatric disorders - additional genes v0.34 CRELD1 Ellen McDonagh gene: CRELD1 was added
gene: CRELD1 was added to Paediatric disorders - additional genes. Sources: South West GLH
Mode of inheritance for gene: CRELD1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: CRELD1 were set to Atrioventricular septal defect, partial, with heterotaxy syndrome; Atrioventricular septal defect, susceptibility to, 2
Paediatric disorders - additional genes v0.34 ZFPM2 Ellen McDonagh gene: ZFPM2 was added
gene: ZFPM2 was added to Paediatric disorders - additional genes. Sources: South West GLH
Mode of inheritance for gene: ZFPM2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: ZFPM2 were set to Tetralogy of Fallot
Paediatric disorders - additional genes v0.34 TLL1 Ellen McDonagh gene: TLL1 was added
gene: TLL1 was added to Paediatric disorders - additional genes. Sources: South West GLH
Mode of inheritance for gene: TLL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TLL1 were set to Atrial septal defect 6
Paediatric disorders - additional genes v0.34 PRDM6 Ellen McDonagh gene: PRDM6 was added
gene: PRDM6 was added to Paediatric disorders - additional genes. Sources: South West GLH
Mode of inheritance for gene: PRDM6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PRDM6 were set to Patent ductus arteriosus 3
Paediatric disorders - additional genes v0.34 NKX2-6 Ellen McDonagh gene: NKX2-6 was added
gene: NKX2-6 was added to Paediatric disorders - additional genes. Sources: South West GLH
Mode of inheritance for gene: NKX2-6 was set to Unknown
Phenotypes for gene: NKX2-6 were set to Conotruncal heart malformations; Persistent truncus arteriosus
Paediatric disorders - additional genes v0.34 GDF1 Ellen McDonagh gene: GDF1 was added
gene: GDF1 was added to Paediatric disorders - additional genes. Sources: South West GLH
Mode of inheritance for gene: GDF1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: GDF1 were set to Right atrial isomerism (Ivemark); Congenital heart defects, multiple types, 6
Paediatric disorders - additional genes v0.34 FOXH1 Ellen McDonagh gene: FOXH1 was added
gene: FOXH1 was added to Paediatric disorders - additional genes. Sources: South West GLH
Mode of inheritance for gene: FOXH1 was set to Unknown
Paediatric disorders - additional genes v0.34 DNAI1 Ellen McDonagh gene: DNAI1 was added
gene: DNAI1 was added to Paediatric disorders - additional genes. Sources: South West GLH
Mode of inheritance for gene: DNAI1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DNAI1 were set to Ciliary dyskinesia, primary, 1, with or without situs inversus
Paediatric disorders - additional genes v0.34 DNAH11 Ellen McDonagh gene: DNAH11 was added
gene: DNAH11 was added to Paediatric disorders - additional genes. Sources: South West GLH
Mode of inheritance for gene: DNAH11 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: DNAH11 were set to Ciliary dyskinesia, primary, 7, with or without situs inversus
Paediatric disorders - additional genes v0.34 STK4 Ellen McDonagh gene: STK4 was added
gene: STK4 was added to Paediatric disorders - additional genes. Sources: South West GLH
Mode of inheritance for gene: STK4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STK4 were set to 22294732; 22174160
Phenotypes for gene: STK4 were set to T-cell immunodeficiency, recurrent infections, autoimmunity, and cardiac malformations
Paediatric disorders - additional genes v0.34 PLD1 Ellen McDonagh gene: PLD1 was added
gene: PLD1 was added to Paediatric disorders - additional genes. Sources: South West GLH
Mode of inheritance for gene: PLD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLD1 were set to 27799408
Phenotypes for gene: PLD1 were set to Cardiac valvular defect, developmental
Paediatric disorders - additional genes v0.34 MYH7 Ellen McDonagh gene: MYH7 was added
gene: MYH7 was added to Paediatric disorders - additional genes. Sources: South West GLH
Mode of inheritance for gene: MYH7 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: MYH7 were set to Cardiomyopathy, dilated, 1S; Left ventricular noncompaction 5; Cardiomyopathy, hypertrophic, 1; Myopathy, myosin storage, autosomal recessive; Myopathy, myosin storage, autosomal dominant; Scapuloperoneal syndrome, myopathic type; Laing distal myopathy
Paediatric disorders - additional genes v0.34 GATA5 Ellen McDonagh gene: GATA5 was added
gene: GATA5 was added to Paediatric disorders - additional genes. Sources: South West GLH
Mode of inheritance for gene: GATA5 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: GATA5 were set to Congenital heart defects, multiple types, 5
Paediatric disorders - additional genes v0.34 CITED2 Ellen McDonagh gene: CITED2 was added
gene: CITED2 was added to Paediatric disorders - additional genes. Sources: South West GLH
Mode of inheritance for gene: CITED2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: CITED2 were set to Atrial septal defect 8; Ventricular septal defect 2
Paediatric disorders - additional genes v0.34 CFAP53 Ellen McDonagh gene: CFAP53 was added
gene: CFAP53 was added to Paediatric disorders - additional genes. Sources: South West GLH
Mode of inheritance for gene: CFAP53 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CFAP53 were set to Heterotaxy, visceral, 6, autosomal recessive
Paediatric disorders - additional genes v0.34 ACTC1 Ellen McDonagh gene: ACTC1 was added
gene: ACTC1 was added to Paediatric disorders - additional genes. Sources: South West GLH
Mode of inheritance for gene: ACTC1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: ACTC1 were set to Atrial septal defect 5; Cardiomyopathy, hypertrophic, 11; Cardiomyopathy, dilated, 1R; Left ventricular noncompaction 4
Paediatric disorders - additional genes v0.33 SOX11 Rebecca Foulger commented on gene: SOX11: Alisdair McNeill (Sheffield Childrens Hospital) review, copied from DDG2P Panel Version: 1.128, Created: 7 Oct 2019, 2:38 p.m.: I have identified a series (unpublished) of around 20 children with de novo variants in SOX11 and overlapping clinical features. I think this is a real, though rare, cause of neurodevelopmental disorders.
Paediatric disorders - additional genes v0.33 SOX11 Rebecca Foulger Mode of inheritance for gene: SOX11 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Paediatric disorders - additional genes v0.32 SOX11 Rebecca Foulger Classified gene: SOX11 as Green List (high evidence)
Paediatric disorders - additional genes v0.32 SOX11 Rebecca Foulger Gene: sox11 has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v0.31 SOX11 Rebecca Foulger gene: SOX11 was added
gene: SOX11 was added to Paediatric disorders - additional genes. Sources: Expert list
Mode of inheritance for gene: SOX11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SOX11 were set to MENTAL RETARDATION, AUTOSOMAL DOMINANT, 27; Coffin-Siris syndrome 9, 615866
Added comment: Added SOX11 to the panel based on a Green review left by Alisdair McNeill (Sheffield Childrens Hospital) for SOX11 on the PanelApp DDG2P panel. SOX11 currently has a probable Disease confidence in Gene2Phenotype for MENTAL RETARDATION, AUTOSOMAL DOMINANT, 27, but Alisdair McNeil's review provides sufficient cases for a Green rating on the Paediatric disorders Super panel.
Sources: Expert list
Paediatric disorders - additional genes v0.30 IARS Louise Daugherty commented on gene: IARS
Paediatric disorders - additional genes v0.28 CFC1 Helen Brittain Classified gene: CFC1 as Green List (high evidence)
Paediatric disorders - additional genes v0.28 CFC1 Helen Brittain Added comment: Comment on list classification: Meets criteria for green rating in 100K - awaiting higher level sign off for GMS indication
Paediatric disorders - additional genes v0.28 CFC1 Helen Brittain Gene: cfc1 has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v0.27 CFC1 Helen Brittain gene: CFC1 was added
gene: CFC1 was added to Paediatric disorders - additional genes. Sources: Literature
Mode of inheritance for gene: CFC1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CFC1 were set to 11062482; 11799476
Phenotypes for gene: CFC1 were set to Heterotaxy, visceral, 2, autosomal 605376
Review for gene: CFC1 was set to GREEN
Added comment: Three unrelated cases with laterality defects with two LOF mutations in PMID 11062482. Also PMID 11799476 reports two cases with congenital cardiac malformations (TGA/DORV). Considered sufficient cases for inclusion.
Sources: Literature
Paediatric disorders - additional genes v0.26 ACVR2B Helen Brittain Classified gene: ACVR2B as Green List (high evidence)
Paediatric disorders - additional genes v0.26 ACVR2B Helen Brittain Added comment: Comment on list classification: Meets criteria for green rating under 100K - awaiting higher level sign off re GMS indication
Paediatric disorders - additional genes v0.26 ACVR2B Helen Brittain Gene: acvr2b has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v0.25 ACVR2B Helen Brittain gene: ACVR2B was added
gene: ACVR2B was added to Paediatric disorders - additional genes. Sources: Literature
Mode of inheritance for gene: ACVR2B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ACVR2B were set to 9916847
Phenotypes for gene: ACVR2B were set to Heterotaxy syndrome Heterotaxy, visceral, 4, autosomal, 613751
Review for gene: ACVR2B was set to GREEN
Added comment: Three unrelated cases of left-right axis malformations, including cardiac anomalies e.g. left atrial isomerism
Sources: Literature
Paediatric disorders - additional genes v0.24 ABL1 Helen Brittain Classified gene: ABL1 as Green List (high evidence)
Paediatric disorders - additional genes v0.24 ABL1 Helen Brittain Added comment: Comment on list classification: Green on 100K criteria - pending higher level sign off for GMS indication
Paediatric disorders - additional genes v0.24 ABL1 Helen Brittain Gene: abl1 has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v0.23 ABL1 Helen Brittain gene: ABL1 was added
gene: ABL1 was added to Paediatric disorders - additional genes. Sources: Literature
missense tags were added to gene: ABL1.
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 Congenital heart defects and skeletal malformations syndrome 617602
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 GREEN
Added comment: "4 unrelated families who exhibited dysmorphic facial features, congenital heart disease, skeletal abnormalities, joint problems, failure to thrive, gastrointestinal problems, and male genital anomalies. In younger children, dysmorphic features included broad forehead, small nose, deep-set eyes, and small chin, whereas in older patients, the face appeared elongated, with a narrow maxilla, long and narrow nose, and pointed chin. Common skeletal abnormalities included pectus excavatum, scoliosis, finger contractures, and hindfoot deformity. Congenital heart defects included atrial and ventricular septal defects, and in older patients, aortic root dilation."

Sufficient cases for a green rating. Note that two missense variants have been reported to date - unclear on mode of pathogenicity.
Sources: Literature
Paediatric disorders - additional genes v0.22 IARS Sarah Leigh Tag new-gene-name tag was added to gene: IARS.
Paediatric disorders - additional genes v0.22 IARS Sarah Leigh commented on gene: IARS
Paediatric disorders - additional genes v0.22 IARS Rebecca Foulger Publications for gene: IARS were set to 27426735
Paediatric disorders - additional genes v0.21 IARS Rebecca Foulger commented on gene: IARS: Helen Brittain reviewed IARS on the 'Intellectual disability' panel' and notes: Early presentation with hypotonia and global delay.
Paediatric disorders - additional genes v0.21 IARS Rebecca Foulger commented on gene: IARS: DD-G2P Disease confidence rating of 'probable' for 'Growth Retardation with Prenatal Onset, Intellectual Disability, Muscular Hypotonia, and Infantile Hepatopathy', but sufficient cases from the literature to support Green rating. As reviewed by Louise Daugherty on the 'Intellectual disability' panel: Kopajtich et al., 2016 PMID:27426735 reported 3 unrelated patients with a multisystem disorder characterized by intrauterine and postnatal growth retardation, including small head circumference (-3 to -5 SD), hypotonia and delayed psychomotor development with variable severity of intellectual disability.
Paediatric disorders - additional genes v0.21 IARS Rebecca Foulger Classified gene: IARS as Green List (high evidence)
Paediatric disorders - additional genes v0.21 IARS Rebecca Foulger Gene: iars has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v0.20 IARS Rebecca Foulger gene: IARS was added
gene: IARS was added to Paediatric disorders - additional genes. Sources: Other
Mode of inheritance for gene: IARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IARS were set to 27426735
Phenotypes for gene: IARS were set to Growth retardation, impaired intellectual development, hypotonia, and hepatopathy, 617093
Added comment: Added to 'Paediatric disorders - additional genes' panel on recommendation of Genomics England clinical team.
Sources: Other
Paediatric disorders - additional genes v0.19 IER3IP1 Rebecca Foulger Classified gene: IER3IP1 as Green List (high evidence)
Paediatric disorders - additional genes v0.19 IER3IP1 Rebecca Foulger Gene: ier3ip1 has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v0.18 IER3IP1 Rebecca Foulger gene: IER3IP1 was added
gene: IER3IP1 was added to Paediatric disorders - additional genes. Sources: Other
Mode of inheritance for gene: IER3IP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IER3IP1 were set to 21835305; 22991235; 24138066
Phenotypes for gene: IER3IP1 were set to Microcephaly, epilepsy, and diabetes syndrome, 614231; MEDS
Added comment: Added to 'Paediatric disorders - additional genes' panel on recommendation of Genomics England clinical team, to allow demotion of gene rating on the 'Mitochondrial disorders' panel.
Sources: Other
Paediatric disorders - additional genes v0.17 Rebecca Foulger Panel types changed to GMS Rare Disease; Component Of Super Panel
Paediatric disorders - additional genes v0.16 TTN Rebecca Foulger changed review comment from: Comment on list classification: Updated rating of TTN on the 'Paediatric disorders - additional genes' panel from Red to Green based on the review Lucy Raymond left on the 'DDG2P' panel. TTN was original Red on the DDG2P panel based on a 'possible' DDG2P Disease confidence for 'CAUSE OF EARLY-ONSET MYOPATHY WITH FATAL CARDIOMYOPATHY' (MOI: biallelic). TTN was upgraded to Green on the 'Fetal anomalies' panel following clinical review, and there are sufficient cases from PMIDs 29691892, 28040389, 29575618) to support inclusion on this paediatric panel.; to: Comment on list classification: Updated rating of TTN on the 'Paediatric disorders - additional genes' panel from Red to Green based on the review Lucy Raymond left on the 'DDG2P' panel. TTN was original Red on the DDG2P panel based on a 'possible' DDG2P Disease confidence for 'CAUSE OF EARLY-ONSET MYOPATHY WITH FATAL CARDIOMYOPATHY' (MOI: biallelic). TTN was upgraded to Green on the 'Fetal anomalies' panel following clinical review, and there are sufficient cases from PMIDs 29691892, 28040389, 29575618 to support inclusion on this paediatric panel.
Paediatric disorders - additional genes v0.16 TTN Rebecca Foulger Classified gene: TTN as Green List (high evidence)
Paediatric disorders - additional genes v0.16 TTN Rebecca Foulger Added comment: Comment on list classification: Updated rating of TTN on the 'Paediatric disorders - additional genes' panel from Red to Green based on the review Lucy Raymond left on the 'DDG2P' panel. TTN was original Red on the DDG2P panel based on a 'possible' DDG2P Disease confidence for 'CAUSE OF EARLY-ONSET MYOPATHY WITH FATAL CARDIOMYOPATHY' (MOI: biallelic). TTN was upgraded to Green on the 'Fetal anomalies' panel following clinical review, and there are sufficient cases from PMIDs 29691892, 28040389, 29575618) to support inclusion on this paediatric panel.
Paediatric disorders - additional genes v0.16 TTN Rebecca Foulger Gene: ttn has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v0.15 ASCC1 Rebecca Foulger Classified gene: ASCC1 as Green List (high evidence)
Paediatric disorders - additional genes v0.15 ASCC1 Rebecca Foulger Added comment: Comment on list classification: Updated rating of ASCC1 on the 'Paediatric disorders - additional genes' panel from Red to Green based on the review Julia Baptista left on the 'DDG2P' panel and the 'Fetal anomalies' panel. ASCC1 was originally Red on the DDG2P panel based on a Gene2Phenotype Disease confidence rating of 'possible' for: Prenatal Spinal Muscular Atrophy and Congenital Bone Fractures (MOI: biallelic). There are sufficient cases to support inclusion as a Green paediatric gene as per Julia Baptista's review. ASCC1 is already Green on the Fetal anomalies panel, and the Arthrogryposis panel.
Paediatric disorders - additional genes v0.15 ASCC1 Rebecca Foulger Gene: ascc1 has been classified as Green List (High Evidence).
Paediatric disorders - additional genes v0.14 ASCC1 Rebecca Foulger Phenotypes for gene: ASCC1 were changed from Prenatal Spinal Muscular Atrophy and Congenital Bone Fractures to Prenatal Spinal Muscular Atrophy and Congenital Bone Fractures; spinal muscular atrophy; arthrogryposis; fetal akinesia; hypotonia; contractures
Paediatric disorders - additional genes v0.13 ASCC1 Rebecca Foulger Publications for gene: ASCC1 were set to 26924529
Paediatric disorders - additional genes v0.12 ASCC1 Rebecca Foulger commented on gene: ASCC1: My review from 18th Nov 2018 was imported from the DDG2P panel.
Paediatric disorders - additional genes v0.12 TTN Rebecca Foulger commented on gene: TTN: My reviews from 19th Nov 2018 and 18th April 2019 were imported from the DDG2P panel.
Paediatric disorders - additional genes v0.12 TTN Rebecca Foulger commented on gene: TTN: ASCC1 was added to this 'Paediatric disorders - additional genes panel' to allow curation of the review by Lucy Raymond left on the DDG2P panel (Review left April 2019).
Paediatric disorders - additional genes v0.12 ASCC1 Rebecca Foulger commented on gene: ASCC1: ASCC1 was added to this 'Paediatric disorders - additional genes panel' to allow curation of the review by Julia Baptista left on the DDG2P panel (Review left March 2019).
Paediatric disorders - additional genes v0.11 TTN Rebecca Foulger gene: TTN was added
gene: TTN was added to Paediatric disorders - additional genes. Sources: Expert Review Red
Mode of inheritance for gene: TTN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TTN were set to 29575618; 17444505; 29691892; 28040389
Phenotypes for gene: TTN were set to CAUSE OF EARLY-ONSET MYOPATHY WITH FATAL CARDIOMYOPATHY
Paediatric disorders - additional genes v0.11 ASCC1 Rebecca Foulger gene: ASCC1 was added
gene: ASCC1 was added to Paediatric disorders - additional genes. Sources: Expert Review Red
Mode of inheritance for gene: ASCC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASCC1 were set to 26924529
Phenotypes for gene: ASCC1 were set to Prenatal Spinal Muscular Atrophy and Congenital Bone Fractures
Paediatric disorders - additional genes v0.9 TRAP1 Rebecca Foulger commented on gene: TRAP1
Paediatric disorders - additional genes v0.9 CDX1 Rebecca Foulger commented on gene: CDX1
Paediatric disorders - additional genes v0.7 CDX1 Rebecca Foulger gene: CDX1 was added
gene: CDX1 was added to Paediatric disorders - additional genes. Sources: Expert Review Green
Mode of inheritance for gene: CDX1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CDX1 were set to 23329892; 27042391
Phenotypes for gene: CDX1 were set to anorectal malformation
Paediatric disorders - additional genes v0.7 TRAP1 Rebecca Foulger gene: TRAP1 was added
gene: TRAP1 was added to Paediatric disorders - additional genes. Sources: Expert Review Green
Mode of inheritance for gene: TRAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAP1 were set to PMID: 24152966 - recessive mutations reported in 2 families with CAKUT, and 3 families with VACTERL.
Phenotypes for gene: TRAP1 were set to CAKUT; VACTERL
Paediatric disorders - additional genes v0.3 Ellen McDonagh Panel status changed from internal to public
Paediatric disorders - additional genes v0.2 Ellen McDonagh Panel status changed from public to internal
Paediatric disorders - additional genes v0.1 Ellen McDonagh Panel types changed to
Paediatric disorders - additional genes v0.0 Ellen McDonagh Added Panel Paediatric disorders - additional genes
Set panel types to: GMS Rare Disease Virtual