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Laterality disorders and isomerism v2.2 CFAP52 Sarah Leigh Source Expert Review Green was added to CFAP52.
Source NHS GMS was added to CFAP52.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Laterality disorders and isomerism v2.2 CFAP45 Sarah Leigh Source Expert Review Green was added to CFAP45.
Source NHS GMS was added to CFAP45.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v2.6 XPNPEP3 Sarah Leigh Tag Q1_22_rating was removed from gene: XPNPEP3.
Unexplained young onset end-stage renal disease v2.6 EMP2 Sarah Leigh Tag Q2_22_rating was removed from gene: EMP2.
Unexplained young onset end-stage renal disease v2.6 CFI Sarah Leigh Tag Q2_22_MOI was removed from gene: CFI.
Unexplained young onset end-stage renal disease v2.6 TTC21B Sarah Leigh Tag Q3_22_MOI was removed from gene: TTC21B.
Tag Q3_22_expert_review was removed from gene: TTC21B.
Unexplained young onset end-stage renal disease v2.6 CHRM3 Sarah Leigh Tag Q3_22_rating was removed from gene: CHRM3.
Unexplained young onset end-stage renal disease v2.6 XPNPEP3 Sarah Leigh commented on gene: XPNPEP3: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Unexplained young onset end-stage renal disease v2.6 EMP2 Sarah Leigh reviewed gene: EMP2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Unexplained young onset end-stage renal disease v2.6 CFI Sarah Leigh commented on gene: CFI: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Unexplained young onset end-stage renal disease v2.6 TTC21B Sarah Leigh commented on gene: TTC21B: The mode of inheritance of this gene has been updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Unexplained young onset end-stage renal disease v2.6 CHRM3 Sarah Leigh reviewed gene: CHRM3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Unexplained young onset end-stage renal disease v2.5 XPNPEP3 Sarah Leigh Source Expert Review Green was added to XPNPEP3.
Source NHS GMS was added to XPNPEP3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v2.5 TTC21B Sarah Leigh Source NHS GMS was added to TTC21B.
Mode of inheritance for gene TTC21B was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v2.5 EMP2 Sarah Leigh Source Expert Review Amber was added to EMP2.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Unexplained young onset end-stage renal disease v2.5 CHRM3 Sarah Leigh Source Expert Review Green was added to CHRM3.
Source NHS GMS was added to CHRM3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease v2.5 CFI Sarah Leigh Source NHS GMS was added to CFI.
Mode of inheritance for gene CFI was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Renal tubulopathies v3.3 SEC61A1 Sarah Leigh Tag Q2_22_rating was removed from gene: SEC61A1.
Tag Q2_22_phenotype was removed from gene: SEC61A1.
Tag Q2_22_expert_review was removed from gene: SEC61A1.
Renal tubulopathies v3.3 RRAGD Sarah Leigh Tag Q3_22_rating was removed from gene: RRAGD.
Tag Q3_22_NHS_review was removed from gene: RRAGD.
Renal tubulopathies v3.3 KCNJ16 Sarah Leigh Tag Q2_22_rating was removed from gene: KCNJ16.
Renal tubulopathies v3.3 CNNM2 Sarah Leigh Tag Q3_22_rating was removed from gene: CNNM2.
Tag Q3_22_MOI was removed from gene: CNNM2.
Tag Q3_22_NHS_review was removed from gene: CNNM2.
Renal tubulopathies v3.3 SEC61A1 Sarah Leigh reviewed gene: SEC61A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Renal tubulopathies v3.3 RRAGD Sarah Leigh reviewed gene: RRAGD: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Renal tubulopathies v3.3 KCNJ16 Sarah Leigh reviewed gene: KCNJ16: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Renal tubulopathies v3.3 CNNM2 Sarah Leigh reviewed gene: CNNM2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Renal tubulopathies v3.2 SEC61A1 Sarah Leigh Source Expert Review Green was added to SEC61A1.
Source NHS GMS was added to SEC61A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Renal tubulopathies v3.2 RRAGD Sarah Leigh Source Expert Review Green was added to RRAGD.
Source NHS GMS was added to RRAGD.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Renal tubulopathies v3.2 KCNJ16 Sarah Leigh Source Expert Review Green was added to KCNJ16.
Source NHS GMS was added to KCNJ16.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Renal tubulopathies v3.2 CNNM2 Sarah Leigh Source Expert Review Green was added to CNNM2.
Source NHS GMS was added to CNNM2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained death in infancy and sudden unexplained death in childhood v3.29 Arina Puzriakova Panel status changed from internal to public
Unexplained death in infancy and sudden unexplained death in childhood v3.27 Arina Puzriakova Panel types changed to GMS Rare Disease Virtual; Super Panel; GMS Rare Disease
Rare genetic inflammatory skin disorders v2.1 COL5A2 Dmitrijs Rots reviewed gene: COL5A2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Rare genetic inflammatory skin disorders v2.1 COL5A1 Dmitrijs Rots reviewed gene: COL5A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Rare genetic inflammatory skin disorders v2.1 COL4A5 Dmitrijs Rots reviewed gene: COL4A5: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Rare genetic inflammatory skin disorders v2.1 COL4A4 Dmitrijs Rots reviewed gene: COL4A4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Rare genetic inflammatory skin disorders v2.1 COL4A3 Dmitrijs Rots reviewed gene: COL4A3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Rare genetic inflammatory skin disorders v2.1 COL3A1 Dmitrijs Rots reviewed gene: COL3A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Rare genetic inflammatory skin disorders v2.1 COL1A2 Dmitrijs Rots reviewed gene: COL1A2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Rare genetic inflammatory skin disorders v2.1 COL1A1 Dmitrijs Rots reviewed gene: COL1A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
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)
Intellectual disability v4.53 CUX2 Arina Puzriakova Tag Q3_21_NHS_review was removed from gene: CUX2.
Intellectual disability v4.53 RAP1GDS1 Arina Puzriakova Tag Q3_22_rating was removed from gene: RAP1GDS1.
Tag Q3_22_expert_review was removed from gene: RAP1GDS1.
Intellectual disability v4.53 ZC4H2 Arina Puzriakova Tag Q4_21_MOI was removed from gene: ZC4H2.
Intellectual disability v4.53 PRODH Arina Puzriakova Tag Q2_22_rating was removed from gene: PRODH.
Tag Q2_22_expert_review was removed from gene: PRODH.
Tag Q2_22_NHS_review was removed from gene: PRODH.
Intellectual disability v4.53 ZBTB7A Arina Puzriakova Tag Q2_22_rating was removed from gene: ZBTB7A.
Tag Q2_22_NHS_review was removed from gene: ZBTB7A.
Intellectual disability v4.53 THUMPD1 Arina Puzriakova Tag Q2_22_rating was removed from gene: THUMPD1.
Tag Q2_22_NHS_review was removed from gene: THUMPD1.
Intellectual disability v4.53 SRRM2 Arina Puzriakova Tag Q2_22_rating was removed from gene: SRRM2.
Intellectual disability v4.53 SPRED2 Arina Puzriakova Tag Q1_22_rating was removed from gene: SPRED2.
Intellectual disability v4.53 SPATA5L1 Arina Puzriakova Tag Q1_22_rating was removed from gene: SPATA5L1.
Intellectual disability v4.53 SNORD118 Arina Puzriakova Tag Q2_22_rating was removed from gene: SNORD118.
Tag Q2_22_NHS_review was removed from gene: SNORD118.
Intellectual disability v4.53 SLC12A5 Arina Puzriakova Tag Q1_22_MOI was removed from gene: SLC12A5.
Intellectual disability v4.53 SCAF4 Arina Puzriakova Tag Q2_22_rating was removed from gene: SCAF4.
Tag Q2_22_NHS_review was removed from gene: SCAF4.
Intellectual disability v4.53 PRPF8 Arina Puzriakova Tag Q2_22_rating was removed from gene: PRPF8.
Intellectual disability v4.53 PHF14 Arina Puzriakova Tag Q2_22_rating was removed from gene: PHF14.
Intellectual disability v4.53 PEX6 Arina Puzriakova Tag Q1_22_MOI was removed from gene: PEX6.
Intellectual disability v4.53 NAPB Arina Puzriakova Tag Q2_22_rating was removed from gene: NAPB.
Tag Q2_22_NHS_review was removed from gene: NAPB.
Intellectual disability v4.53 MED13 Arina Puzriakova Tag Q2_22_rating was removed from gene: MED13.
Tag Q2_22_NHS_review was removed from gene: MED13.
Intellectual disability v4.53 KDM5C Arina Puzriakova Tag Q3_21_MOI was removed from gene: KDM5C.
Intellectual disability v4.53 HSPD1 Arina Puzriakova Tag Q2_22_MOI was removed from gene: HSPD1.
Intellectual disability v4.53 DTYMK Arina Puzriakova Tag Q2_22_rating was removed from gene: DTYMK.
Intellectual disability v4.53 DROSHA Arina Puzriakova Tag Q2_22_rating was removed from gene: DROSHA.
Intellectual disability v4.53 DHDDS Arina Puzriakova Tag Q4_21_MOI was removed from gene: DHDDS.
Intellectual disability v4.53 COG5 Arina Puzriakova Tag Q3_21_MOI was removed from gene: COG5.
Intellectual disability v4.53 CELF2 Arina Puzriakova Tag Q2_22_rating was removed from gene: CELF2.
Tag Q2_22_NHS_review was removed from gene: CELF2.
Intellectual disability v4.53 CACNA2D1 Arina Puzriakova Tag Q2_22_rating was removed from gene: CACNA2D1.
Intellectual disability v4.53 BSCL2 Arina Puzriakova Tag Q3_21_MOI was removed from gene: BSCL2.
Intellectual disability v4.53 ARHGEF9 Arina Puzriakova Tag Q3_21_MOI was removed from gene: ARHGEF9.
Intellectual disability v4.53 AP1S2 Arina Puzriakova Tag Q4_21_MOI was removed from gene: AP1S2.
Intellectual disability v4.53 AFF3 Arina Puzriakova Tag for-review was removed from gene: AFF3.
Intellectual disability v4.53 ACO2 Arina Puzriakova Tag Q2_22_MOI was removed from gene: ACO2.
Intellectual disability v4.53 ACER3 Arina Puzriakova Tag Q1_22_rating was removed from gene: ACER3.
Intellectual disability v4.53 ZMYM2 Arina Puzriakova Tag Q3_22_rating was removed from gene: ZMYM2.
Tag Q3_22_NHS_review was removed from gene: ZMYM2.
Intellectual disability v4.53 WNK3 Arina Puzriakova Tag Q3_22_rating was removed from gene: WNK3.
Intellectual disability v4.53 TPP2 Arina Puzriakova Tag Q3_22_rating was removed from gene: TPP2.
Intellectual disability v4.53 TMEM63C Arina Puzriakova Tag Q3_22_rating was removed from gene: TMEM63C.
Intellectual disability v4.53 TIAM1 Arina Puzriakova Tag Q3_22_rating was removed from gene: TIAM1.
Tag Q3_22_MOI was removed from gene: TIAM1.
Intellectual disability v4.53 TAF8 Arina Puzriakova Tag Q3_22_rating was removed from gene: TAF8.
Tag Q3_22_NHS_review was removed from gene: TAF8.
Proteinuric renal disease v3.3 GLA Sarah Leigh Tag Q3_22_rating was removed from gene: GLA.
Tag Q3_22_NHS_review was removed from gene: GLA.
Proteinuric renal disease v3.3 EMP2 Sarah Leigh Tag Q2_22_rating was removed from gene: EMP2.
Tag Q2_22_expert_review was removed from gene: EMP2.
Proteinuric renal disease v3.3 GLA Sarah Leigh reviewed gene: GLA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Proteinuric renal disease v3.3 EMP2 Sarah Leigh reviewed gene: EMP2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Proteinuric renal disease v3.2 GLA Sarah Leigh Source Expert Review Green was added to GLA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Proteinuric renal disease v3.2 EMP2 Sarah Leigh Source Expert Review Amber was added to EMP2.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v2.10 TOR1A Eleanor Williams Tag Q1_22_MOI was removed from gene: TOR1A.
Childhood onset dystonia, chorea or related movement disorder v2.10 TOR1A Eleanor Williams changed review comment from: The mode of inheritance of this gene has been updated toBOTH monoallelic and biallelic, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v2.10 SPATA5L1 Eleanor Williams Tag Q1_22_rating was removed from gene: SPATA5L1.
Childhood onset dystonia, chorea or related movement disorder v2.10 SPATA5L1 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v2.10 SNORD118 Eleanor Williams Tag Q2_22_rating was removed from gene: SNORD118.
Childhood onset dystonia, chorea or related movement disorder v2.10 SNORD118 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v2.10 PNPT1 Eleanor Williams Tag Q1_22_rating was removed from gene: PNPT1.
Childhood onset dystonia, chorea or related movement disorder v2.10 PNPT1 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v2.10 NDUFA12 Eleanor Williams Tag Q3_22_rating was removed from gene: NDUFA12.
Childhood onset dystonia, chorea or related movement disorder v2.10 NDUFA12 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v2.10 HSPD1 Eleanor Williams Tag Q2_22_MOI was removed from gene: HSPD1.
Childhood onset dystonia, chorea or related movement disorder v2.10 HSPD1 Eleanor Williams changed review comment from: The mode of inheritance of this gene has been updated toBIALLELIC, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v2.10 HECW2 Eleanor Williams Tag Q3_22_rating was removed from gene: HECW2.
Childhood onset dystonia, chorea or related movement disorder v2.10 HECW2 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set toMONOALLELIC, autosomal or pseudoautosomal, imprinted status unknownfollowing NHS Genomic Medicine Service approval.; to: 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.
Childhood onset dystonia, chorea or related movement disorder v2.10 ATP5G3 Eleanor Williams Tag Q3_22_rating was removed from gene: ATP5G3.
Childhood onset dystonia, chorea or related movement disorder v2.10 ATP5G3 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set toMONOALLELIC, autosomal or pseudoautosomal, NOT imprintedfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v2.10 AP1S2 Eleanor Williams Tag Q4_21_MOI was removed from gene: AP1S2.
Childhood onset dystonia, chorea or related movement disorder v2.10 AP1S2 Eleanor Williams changed review comment from: The mode of inheritance of this gene has been updated toX-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)following NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v2.10 ACER3 Eleanor Williams Tag Q1_22_rating was removed from gene: ACER3.
Childhood onset dystonia, chorea or related movement disorder v2.10 ACER3 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.; to: 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.
Childhood onset dystonia, chorea or related movement disorder v2.10 CACNB4 Eleanor Williams changed review comment from: The mode of inheritance of this gene has been updated toBOTH monoallelic and biallelic, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v2.10 TOR1A Eleanor Williams commented on gene: TOR1A
Childhood onset dystonia, chorea or related movement disorder v2.10 SPATA5L1 Eleanor Williams reviewed gene: SPATA5L1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood onset dystonia, chorea or related movement disorder v2.10 SNORD118 Eleanor Williams reviewed gene: SNORD118: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood onset dystonia, chorea or related movement disorder v2.10 PNPT1 Eleanor Williams reviewed gene: PNPT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood onset dystonia, chorea or related movement disorder v2.10 NDUFA12 Eleanor Williams reviewed gene: NDUFA12: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood onset dystonia, chorea or related movement disorder v2.10 HSPD1 Eleanor Williams commented on gene: HSPD1
Childhood onset dystonia, chorea or related movement disorder v2.10 HECW2 Eleanor Williams reviewed gene: HECW2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood onset dystonia, chorea or related movement disorder v2.10 COL6A3 Eleanor Williams commented on gene: COL6A3: The mode of inheritance of this gene has been updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v2.10 CACNB4 Eleanor Williams commented on gene: CACNB4
Childhood onset dystonia, chorea or related movement disorder v2.10 ATP5G3 Eleanor Williams reviewed gene: ATP5G3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood onset dystonia, chorea or related movement disorder v2.10 AP1S2 Eleanor Williams commented on gene: AP1S2
Childhood onset dystonia, chorea or related movement disorder v2.10 ACER3 Eleanor Williams reviewed gene: ACER3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v2.46 TTR Sarah Leigh Tag Q1_23_promote_green was removed from gene: TTR.
Tag Q1_23_NHS_review was removed from gene: TTR.
Adult onset leukodystrophy v2.46 PSEN1 Sarah Leigh Tag Q1_23_promote_green was removed from gene: PSEN1.
Tag Q1_23_NHS_review was removed from gene: PSEN1.
Adult onset leukodystrophy v2.46 PRNP Sarah Leigh Tag Q1_23_promote_green was removed from gene: PRNP.
Tag Q1_23_NHS_review was removed from gene: PRNP.
Adult onset leukodystrophy v2.46 ITM2B Sarah Leigh Tag Q1_23_promote_green was removed from gene: ITM2B.
Tag Q1_23_NHS_review was removed from gene: ITM2B.
Adult onset leukodystrophy v2.46 GSN Sarah Leigh Tag Q1_23_promote_green was removed from gene: GSN.
Tag Q1_23_NHS_review was removed from gene: GSN.
Adult onset leukodystrophy v2.46 APP Sarah Leigh Tag Q1_23_promote_green was removed from gene: APP.
Adult onset leukodystrophy v2.46 APP Sarah Leigh changed review comment from: The rating of this gene has been updated to Green and the mode of inheritance set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) following NHS Genomic Medicine Service approval.; to: 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.
Adult onset leukodystrophy v2.46 LAMB1 Sarah Leigh Tag Q1_23_promote_green was removed from gene: LAMB1.
Tag Q1_23_MOI was removed from gene: LAMB1.
Tag Q1_23_NHS_review was removed from gene: LAMB1.
Adult onset leukodystrophy v2.46 PSEN2 Sarah Leigh Tag Q1_23_promote_green was removed from gene: PSEN2.
Tag Q1_23_NHS_review was removed from gene: PSEN2.
Childhood onset dystonia, chorea or related movement disorder v2.9 FXN_GAA Eleanor Williams reviewed STR: FXN_GAA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Childhood onset dystonia, chorea or related movement disorder v2.9 FXN_GAA Eleanor Williams Tag Q2_21_rating was removed from STR: FXN_GAA.
Childhood onset dystonia, chorea or related movement disorder v2.9 FXN_GAA Eleanor Williams Classified STR: FXN_GAA as Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v2.9 FXN_GAA Eleanor Williams Str: fxn_gaa has been classified as Green List (High Evidence).
Adult onset leukodystrophy v2.46 PSEN2 Sarah Leigh changed review comment from: 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.; to: The rating of this gene has been updated to Amber and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.
Adult onset leukodystrophy v2.46 GLA Sarah Leigh Tag Q3_22_MOI was removed from gene: GLA.
Intellectual disability v4.53 STT3A Arina Puzriakova Tag Q3_22_MOI was removed from gene: STT3A.
Tag Q3_22_NHS_review was removed from gene: STT3A.
Intellectual disability v4.53 SLC38A3 Arina Puzriakova Tag Q3_22_rating was removed from gene: SLC38A3.
Intellectual disability v4.53 SCAMP5 Arina Puzriakova Tag Q3_22_rating was removed from gene: SCAMP5.
Intellectual disability v4.53 RAB11A Arina Puzriakova Tag watchlist was removed from gene: RAB11A.
Tag Q3_22_rating was removed from gene: RAB11A.
Intellectual disability v4.53 PRDM13 Arina Puzriakova Tag Q3_22_rating was removed from gene: PRDM13.
Intellectual disability v4.53 POLRMT Arina Puzriakova Tag Q3_22_rating was removed from gene: POLRMT.
Intellectual disability v4.53 PDZD8 Arina Puzriakova Tag Q3_22_rating was removed from gene: PDZD8.
Childhood onset dystonia, chorea or related movement disorder v2.8 TOR1A Eleanor Williams Mode of inheritance for gene TOR1A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v2.8 SPATA5L1 Eleanor Williams Source Expert Review Green was added to SPATA5L1.
Source NHS GMS was added to SPATA5L1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v2.8 SNORD118 Eleanor Williams Source Expert Review Green was added to SNORD118.
Source NHS GMS was added to SNORD118.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v2.8 PNPT1 Eleanor Williams Source Expert Review Green was added to PNPT1.
Source NHS GMS was added to PNPT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v2.8 NDUFA12 Eleanor Williams Source Expert Review Green was added to NDUFA12.
Source NHS GMS was added to NDUFA12.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v2.8 HSPD1 Eleanor Williams Mode of inheritance for gene HSPD1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v2.8 HECW2 Eleanor Williams Source Expert Review Green was added to HECW2.
Source NHS GMS was added to HECW2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v2.8 COL6A3 Eleanor Williams Mode of inheritance for gene COL6A3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v2.8 CACNB4 Eleanor Williams Source NHS GMS was added to CACNB4.
Mode of inheritance for gene CACNB4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v2.8 ATP5G3 Eleanor Williams Source Expert Review Green was added to ATP5G3.
Source NHS GMS was added to ATP5G3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v2.8 AP1S2 Eleanor Williams Mode of inheritance for gene AP1S2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Childhood onset dystonia, chorea or related movement disorder v2.8 ACER3 Eleanor Williams Source Expert Review Green was added to ACER3.
Source NHS GMS was added to ACER3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.53 OGDHL Arina Puzriakova Tag Q3_22_rating was removed from gene: OGDHL.
Intellectual disability v4.53 NSRP1 Arina Puzriakova Tag Q3_22_rating was removed from gene: NSRP1.
Intellectual disability v4.53 NRCAM Arina Puzriakova Tag Q3_22_rating was removed from gene: NRCAM.
Intellectual disability v4.53 HMGB1 Arina Puzriakova Tag Q3_22_rating was removed from gene: HMGB1.
Intellectual disability v4.53 HK1 Arina Puzriakova Tag Q3_22_MOI was removed from gene: HK1.
Tag Q3_22_NHS_review was removed from gene: HK1.
Intellectual disability v4.53 GLRA2 Arina Puzriakova Tag Q3_22_rating was removed from gene: GLRA2.
Intellectual disability v4.53 FBXW7 Arina Puzriakova Tag Q3_22_rating was removed from gene: FBXW7.
Tag Q3_22_MOI was removed from gene: FBXW7.
Intellectual disability v4.53 FBXO28 Arina Puzriakova Tag Q3_22_rating was removed from gene: FBXO28.
Tag Q3_22_MOI was removed from gene: FBXO28.
Intellectual disability v4.53 EMC1 Arina Puzriakova Tag Q3_22_MOI was removed from gene: EMC1.
Intellectual disability v4.53 EDEM3 Arina Puzriakova Tag Q3_22_rating was removed from gene: EDEM3.
Intellectual disability v4.53 DOCK8 Arina Puzriakova Tag Q3_22_rating was removed from gene: DOCK8.
Tag Q3_22_MOI was removed from gene: DOCK8.
Tag Q3_22_NHS_review was removed from gene: DOCK8.
Tag Q3_22_expert_review was removed from gene: DOCK8.
Adult onset leukodystrophy v2.46 TTR Sarah Leigh commented on gene: TTR: 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.
Adult onset leukodystrophy v2.46 PSEN2 Sarah Leigh edited their review of gene: PSEN2: Added comment: 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.; Changed rating: AMBER
Adult onset leukodystrophy v2.46 PSEN1 Sarah Leigh commented on gene: PSEN1: 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.
Adult onset leukodystrophy v2.46 PRNP Sarah Leigh commented on gene: PRNP: 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.
Adult onset leukodystrophy v2.46 LAMB1 Sarah Leigh commented on gene: LAMB1: The rating of this gene has been updated to Green and the mode of inheritance set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Adult onset leukodystrophy v2.46 ITM2B Sarah Leigh commented on gene: ITM2B: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Adult onset leukodystrophy v2.46 GSN Sarah Leigh commented on gene: GSN: The rating of this gene has been updated to Green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Adult onset leukodystrophy v2.46 GLA Sarah Leigh reviewed gene: GLA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v2.46 CST3 Sarah Leigh commented on gene: CST3: The rating of this gene has been updated to Amber and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.
Adult onset leukodystrophy v2.46 APP Sarah Leigh reviewed gene: APP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset leukodystrophy v2.45 TTR Sarah Leigh Source Expert Review Green was added to TTR.
Source NHS GMS was added to TTR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset leukodystrophy v2.45 PSEN2 Sarah Leigh Source NHS GMS was added to PSEN2.
Adult onset leukodystrophy v2.45 PSEN1 Sarah Leigh Source Expert Review Green was added to PSEN1.
Source NHS GMS was added to PSEN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset leukodystrophy v2.45 PRNP Sarah Leigh Source Expert Review Green was added to PRNP.
Source NHS GMS was added to PRNP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset leukodystrophy v2.45 LAMB1 Sarah Leigh Source Expert Review Green was added to LAMB1.
Source NHS GMS was added to LAMB1.
Mode of inheritance for gene LAMB1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset leukodystrophy v2.45 ITM2B Sarah Leigh Source Expert Review Green was added to ITM2B.
Source NHS GMS was added to ITM2B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset leukodystrophy v2.45 GSN Sarah Leigh Source Expert Review Green was added to GSN.
Source NHS GMS was added to GSN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset leukodystrophy v2.45 GLA Sarah Leigh Mode of inheritance for gene GLA was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Adult onset leukodystrophy v2.45 CST3 Sarah Leigh Source NHS GMS was added to CST3.
Adult onset leukodystrophy v2.45 APP Sarah Leigh Source Expert Review Green was added to APP.
Source NHS GMS was added to APP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.53 CUL3 Arina Puzriakova Tag Q3_22_rating was removed from gene: CUL3.
Tag Q3_22_NHS_review was removed from gene: CUL3.
Intellectual disability v4.53 CHKA Arina Puzriakova Tag Q3_22_rating was removed from gene: CHKA.
Intellectual disability v4.53 CCDC32 Arina Puzriakova Tag watchlist was removed from gene: CCDC32.
Tag Q3_22_rating was removed from gene: CCDC32.
Intellectual disability v4.53 CACNA1A Arina Puzriakova Tag Q3_22_MOI was removed from gene: CACNA1A.
Intellectual disability v4.53 BLOC1S1 Arina Puzriakova Tag Q3_22_rating was removed from gene: BLOC1S1.
Intellectual disability v4.53 ATP6V0A1 Arina Puzriakova Tag Q3_22_rating was removed from gene: ATP6V0A1.
Tag Q3_22_NHS_review was removed from gene: ATP6V0A1.
Intellectual disability v4.53 ATP2B1 Arina Puzriakova Tag Q3_22_rating was removed from gene: ATP2B1.
Intellectual disability v4.53 ATG7 Arina Puzriakova Tag Q3_22_rating was removed from gene: ATG7.
Intellectual disability v4.53 ANK3 Arina Puzriakova Tag Q3_22_rating was removed from gene: ANK3.
Tag Q3_22_MOI was removed from gene: ANK3.
Tag Q3_22_NHS_review was removed from gene: ANK3.
Intellectual disability v4.53 ALKBH8 Arina Puzriakova Tag Q3_22_rating was removed from gene: ALKBH8.
Intellectual disability v4.53 ADD1 Arina Puzriakova Tag Q3_22_rating was removed from gene: ADD1.
Intellectual disability v4.53 PHF14 Arina Puzriakova reviewed gene: PHF14: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 DROSHA Arina Puzriakova reviewed gene: DROSHA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 RAP1GDS1 Arina Puzriakova edited their review of gene: RAP1GDS1: Added comment: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber.; Changed rating: AMBER
Intellectual disability v4.53 PRODH Arina Puzriakova reviewed gene: PRODH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 ZC4H2 Arina Puzriakova commented on gene: ZC4H2
Intellectual disability v4.53 ZBTB7A Arina Puzriakova reviewed gene: ZBTB7A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 THUMPD1 Arina Puzriakova reviewed gene: THUMPD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 SRRM2 Arina Puzriakova reviewed gene: SRRM2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 SPRED2 Arina Puzriakova reviewed gene: SPRED2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 SPATA5L1 Arina Puzriakova reviewed gene: SPATA5L1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 SNORD118 Arina Puzriakova reviewed gene: SNORD118: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 SLC12A5 Arina Puzriakova commented on gene: SLC12A5
Intellectual disability v4.53 SCAF4 Arina Puzriakova edited their review of gene: SCAF4: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v4.53 PRPF8 Arina Puzriakova reviewed gene: PRPF8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 PEX6 Arina Puzriakova commented on gene: PEX6
Intellectual disability v4.53 NAPB Arina Puzriakova edited their review of gene: NAPB: 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
Intellectual disability v4.53 MED13 Arina Puzriakova reviewed gene: MED13: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 KDM5C Arina Puzriakova commented on gene: KDM5C: The mode of inheritance of this gene has been updated to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' following NHS Genomic Medicine Service approval.
Intellectual disability v4.53 HSPD1 Arina Puzriakova commented on gene: HSPD1: The mode of inheritance of this gene has been updated to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Intellectual disability v4.53 DTYMK Arina Puzriakova reviewed gene: DTYMK: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 DHDDS Arina Puzriakova commented on gene: DHDDS: The mode of inheritance of this gene has been updated to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.
Intellectual disability v4.53 COG5 Arina Puzriakova commented on gene: COG5
Intellectual disability v4.53 CELF2 Arina Puzriakova edited their review of gene: CELF2: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v4.53 CACNA2D1 Arina Puzriakova reviewed gene: CACNA2D1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 BSCL2 Arina Puzriakova commented on gene: BSCL2: The mode of inheritance of this gene has been updated to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Intellectual disability v4.53 ARHGEF9 Arina Puzriakova commented on gene: ARHGEF9: The mode of inheritance of this gene has been updated to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' following NHS Genomic Medicine Service approval.
Intellectual disability v4.53 AP1S2 Arina Puzriakova commented on gene: AP1S2: The mode of inheritance of this gene has been updated to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' following NHS Genomic Medicine Service approval.
Intellectual disability v4.53 AFF3 Arina Puzriakova edited their review of gene: AFF3: Added comment: The rating of this gene has been updated to Green and the mode of inheritance updated to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v4.53 ACO2 Arina Puzriakova commented on gene: ACO2
Intellectual disability v4.53 ACER3 Arina Puzriakova commented on gene: ACER3: 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.
Intellectual disability v4.53 ZMYM2 Arina Puzriakova reviewed gene: ZMYM2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 WNK3 Arina Puzriakova commented on gene: WNK3: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Intellectual disability v4.53 TPP2 Arina Puzriakova reviewed gene: TPP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 TMEM63C Arina Puzriakova reviewed gene: TMEM63C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 TIAM1 Arina Puzriakova reviewed gene: TIAM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 TAF8 Arina Puzriakova edited their review of gene: TAF8: 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
Intellectual disability v4.53 STT3A Arina Puzriakova commented on gene: STT3A: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Intellectual disability v4.53 SLC38A3 Arina Puzriakova reviewed gene: SLC38A3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 SCAMP5 Arina Puzriakova reviewed gene: SCAMP5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 RAB11A Arina Puzriakova reviewed gene: RAB11A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 PRDM13 Arina Puzriakova reviewed gene: PRDM13: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 POLRMT Arina Puzriakova edited their review of gene: POLRMT: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v4.53 PDZD8 Arina Puzriakova reviewed gene: PDZD8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 OGDHL Arina Puzriakova edited their review of gene: OGDHL: 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
Intellectual disability v4.53 NSRP1 Arina Puzriakova edited their review of gene: NSRP1: 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
Intellectual disability v4.53 NRCAM Arina Puzriakova reviewed gene: NRCAM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 HMGB1 Arina Puzriakova edited their review of gene: HMGB1: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v4.53 HK1 Arina Puzriakova commented on gene: HK1
Intellectual disability v4.53 GLRA2 Arina Puzriakova reviewed gene: GLRA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 FBXW7 Arina Puzriakova reviewed gene: FBXW7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 FBXO28 Arina Puzriakova reviewed gene: FBXO28: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 EMC1 Arina Puzriakova commented on gene: EMC1
Intellectual disability v4.53 EDEM3 Arina Puzriakova edited their review of gene: EDEM3: 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
Intellectual disability v4.53 DOCK8 Arina Puzriakova reviewed gene: DOCK8: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 CUL3 Arina Puzriakova edited their review of gene: CUL3: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v4.53 CHKA Arina Puzriakova reviewed gene: CHKA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 CCDC32 Arina Puzriakova reviewed gene: CCDC32: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 CACNA1A Arina Puzriakova commented on gene: CACNA1A
Intellectual disability v4.53 BLOC1S1 Arina Puzriakova edited their review of gene: BLOC1S1: 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
Intellectual disability v4.53 ATP6V0A1 Arina Puzriakova reviewed gene: ATP6V0A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 ATP2B1 Arina Puzriakova reviewed gene: ATP2B1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 ATG7 Arina Puzriakova edited their review of gene: ATG7: 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
Intellectual disability v4.53 ANK3 Arina Puzriakova reviewed gene: ANK3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.53 ALKBH8 Arina Puzriakova commented on gene: ALKBH8: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Intellectual disability v4.53 ADD1 Arina Puzriakova reviewed gene: ADD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v4.52 ZMYM2 Arina Puzriakova Source NHS GMS was added to ZMYM2.
Source Expert Review Green was added to ZMYM2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 ZC4H2 Arina Puzriakova Source NHS GMS was added to ZC4H2.
Mode of inheritance for gene ZC4H2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v4.52 ZBTB7A Arina Puzriakova Source NHS GMS was added to ZBTB7A.
Source Expert Review Green was added to ZBTB7A.
Mode of inheritance for gene ZBTB7A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 WNK3 Arina Puzriakova Source NHS GMS was added to WNK3.
Source Expert Review Green was added to WNK3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 TPP2 Arina Puzriakova Source NHS GMS was added to TPP2.
Source Expert Review Green was added to TPP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 TMEM63C Arina Puzriakova Source NHS GMS was added to TMEM63C.
Source Expert Review Green was added to TMEM63C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 TIAM1 Arina Puzriakova Source NHS GMS was added to TIAM1.
Source Expert Review Green was added to TIAM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 THUMPD1 Arina Puzriakova Source NHS GMS was added to THUMPD1.
Source Expert Review Green was added to THUMPD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 TAF8 Arina Puzriakova Source NHS GMS was added to TAF8.
Source Expert Review Green was added to TAF8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 STT3A Arina Puzriakova Source NHS GMS was added to STT3A.
Mode of inheritance for gene STT3A was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v4.52 SRRM2 Arina Puzriakova Source NHS GMS was added to SRRM2.
Source Expert Review Green was added to SRRM2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 SPRED2 Arina Puzriakova Source NHS GMS was added to SPRED2.
Source Expert Review Green was added to SPRED2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 SPATA5L1 Arina Puzriakova Source NHS GMS was added to SPATA5L1.
Source Expert Review Green was added to SPATA5L1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 SNORD118 Arina Puzriakova Source NHS GMS was added to SNORD118.
Source Expert Review Green was added to SNORD118.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 SLC38A3 Arina Puzriakova Source NHS GMS was added to SLC38A3.
Source Expert Review Green was added to SLC38A3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 SLC12A5 Arina Puzriakova Source NHS GMS was added to SLC12A5.
Mode of inheritance for gene SLC12A5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.52 SCAMP5 Arina Puzriakova Source Expert Review Green was added to SCAMP5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 SCAF4 Arina Puzriakova Source NHS GMS was added to SCAF4.
Source Expert Review Green was added to SCAF4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 RAB11A Arina Puzriakova Source NHS GMS was added to RAB11A.
Source Expert Review Green was added to RAB11A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 PRPF8 Arina Puzriakova Source NHS GMS was added to PRPF8.
Source Expert Review Green was added to PRPF8.
Mode of inheritance for gene PRPF8 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 PRODH Arina Puzriakova Source Expert Review Amber was added to PRODH.
Source NHS GMS was added to PRODH.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Intellectual disability v4.52 PRDM13 Arina Puzriakova Source NHS GMS was added to PRDM13.
Source Expert Review Green was added to PRDM13.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 POLRMT Arina Puzriakova Source Expert Review Green was added to POLRMT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 PHF14 Arina Puzriakova Source NHS GMS was added to PHF14.
Intellectual disability v4.52 PEX6 Arina Puzriakova Source NHS GMS was added to PEX6.
Mode of inheritance for gene PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v4.52 PDZD8 Arina Puzriakova Source NHS GMS was added to PDZD8.
Source Expert Review Green was added to PDZD8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 OGDHL Arina Puzriakova Source NHS GMS was added to OGDHL.
Source Expert Review Green was added to OGDHL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 NSRP1 Arina Puzriakova Source NHS GMS was added to NSRP1.
Source Expert Review Green was added to NSRP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 NRCAM Arina Puzriakova Source NHS GMS was added to NRCAM.
Source Expert Review Green was added to NRCAM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 NAPB Arina Puzriakova Source Expert Review Green was added to NAPB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 MED13 Arina Puzriakova Source NHS GMS was added to MED13.
Source Expert Review Green was added to MED13.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 KDM5C Arina Puzriakova Source NHS GMS was added to KDM5C.
Mode of inheritance for gene KDM5C was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v4.52 HSPD1 Arina Puzriakova Source NHS GMS was added to HSPD1.
Mode of inheritance for gene HSPD1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.52 HMGB1 Arina Puzriakova Source NHS GMS was added to HMGB1.
Source Expert Review Green was added to HMGB1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 HK1 Arina Puzriakova Source NHS GMS was added to HK1.
Mode of inheritance for gene HK1 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.52 GLRA2 Arina Puzriakova Source NHS GMS was added to GLRA2.
Source Expert Review Green was added to GLRA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 FBXW7 Arina Puzriakova Source NHS GMS was added to FBXW7.
Source Expert Review Green was added to FBXW7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 FBXO28 Arina Puzriakova Source NHS GMS was added to FBXO28.
Source Expert Review Green was added to FBXO28.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 EMC1 Arina Puzriakova Source NHS GMS was added to EMC1.
Mode of inheritance for gene EMC1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v4.52 EDEM3 Arina Puzriakova Source NHS GMS was added to EDEM3.
Source Expert Review Green was added to EDEM3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 DTYMK Arina Puzriakova Source NHS GMS was added to DTYMK.
Source Expert Review Green was added to DTYMK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 DROSHA Arina Puzriakova Source NHS GMS was added to DROSHA.
Intellectual disability v4.52 DOCK8 Arina Puzriakova Source Expert Review Amber was added to DOCK8.
Source NHS GMS was added to DOCK8.
Mode of inheritance for gene DOCK8 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Intellectual disability v4.52 DHDDS Arina Puzriakova Source NHS GMS was added to DHDDS.
Mode of inheritance for gene DHDDS was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.52 CUL3 Arina Puzriakova Source NHS GMS was added to CUL3.
Source Expert Review Green was added to CUL3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 COG5 Arina Puzriakova Source NHS GMS was added to COG5.
Mode of inheritance for gene COG5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.52 CHKA Arina Puzriakova Source NHS GMS was added to CHKA.
Source Expert Review Green was added to CHKA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 CELF2 Arina Puzriakova Source NHS GMS was added to CELF2.
Source Expert Review Green was added to CELF2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 CCDC32 Arina Puzriakova Source NHS GMS was added to CCDC32.
Source Expert Review Green was added to CCDC32.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 CACNA2D1 Arina Puzriakova Source NHS GMS was added to CACNA2D1.
Source Expert Review Green was added to CACNA2D1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 CACNA1A Arina Puzriakova Source NHS GMS was added to CACNA1A.
Mode of inheritance for gene CACNA1A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v4.52 BSCL2 Arina Puzriakova Source NHS GMS was added to BSCL2.
Mode of inheritance for gene BSCL2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.52 BLOC1S1 Arina Puzriakova Source NHS GMS was added to BLOC1S1.
Source Expert Review Green was added to BLOC1S1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 ATP6V0A1 Arina Puzriakova Source NHS GMS was added to ATP6V0A1.
Source Expert Review Green was added to ATP6V0A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 ATP2B1 Arina Puzriakova Source NHS GMS was added to ATP2B1.
Source Expert Review Green was added to ATP2B1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 ATG7 Arina Puzriakova Source NHS GMS was added to ATG7.
Source Expert Review Green was added to ATG7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 ARHGEF9 Arina Puzriakova Source NHS GMS was added to ARHGEF9.
Mode of inheritance for gene ARHGEF9 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v4.52 AP1S2 Arina Puzriakova Source NHS GMS was added to AP1S2.
Mode of inheritance for gene AP1S2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Intellectual disability v4.52 ANK3 Arina Puzriakova Source NHS GMS was added to ANK3.
Source Expert Review Green was added to ANK3.
Mode of inheritance for gene ANK3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 ALKBH8 Arina Puzriakova Source NHS GMS was added to ALKBH8.
Source Expert Review Green was added to ALKBH8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 AFF3 Arina Puzriakova Source NHS GMS was added to AFF3.
Source Expert Review Green was added to AFF3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 ADD1 Arina Puzriakova Source NHS GMS was added to ADD1.
Source Expert Review Green was added to ADD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v4.52 ACO2 Arina Puzriakova Source NHS GMS was added to ACO2.
Mode of inheritance for gene ACO2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v4.52 ACER3 Arina Puzriakova Source NHS GMS was added to ACER3.
Source Expert Review Green was added to ACER3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Inherited polyposis and early onset colorectal cancer - germline testing v2.4 MBD4 Arina Puzriakova Tag Q3_22_rating was removed from gene: MBD4.
Tag Q3_22_NHS_review was removed from gene: MBD4.
Tag Q3_22_expert_review was removed from gene: MBD4.
Inherited polyposis and early onset colorectal cancer - germline testing v2.4 MBD4 Arina Puzriakova Source NHS GMS was added to MBD4.
Inherited polyposis and early onset colorectal cancer - germline testing v2.3 MBD4 Arina Puzriakova commented on gene: MBD4: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber.
Inherited ovarian cancer (without breast cancer) v3.3 BRCA1 Arina Puzriakova Tag Q2_22_MOI was removed from gene: BRCA1.
Tag Q2_22_expert_review was removed from gene: BRCA1.
Inherited ovarian cancer (without breast cancer) v3.3 BRCA1 Arina Puzriakova commented on gene: BRCA1: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Inherited ovarian cancer (without breast cancer) v3.2 BRCA1 Arina Puzriakova Mode of inheritance for gene BRCA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Inherited breast cancer and ovarian cancer v1.3 BRCA1 Arina Puzriakova Tag Q2_22_MOI was removed from gene: BRCA1.
Tag Q2_22_expert_review was removed from gene: BRCA1.
Inherited breast cancer and ovarian cancer v1.3 BRCA1 Arina Puzriakova Source NHS GMS was added to BRCA1.
Mode of inheritance for gene BRCA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Inherited breast cancer and ovarian cancer v1.2 BRCA1 Arina Puzriakova commented on gene: BRCA1: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Fetal anomalies v2.10 SCUBE3 Arina Puzriakova Tag to_be_confirmed_NHSE tag was added to gene: SCUBE3.
Fetal anomalies v2.10 RAB11A Arina Puzriakova Tag to_be_confirmed_NHSE tag was added to gene: RAB11A.
Fetal anomalies v2.10 MED12 Arina Puzriakova Tag to_be_confirmed_NHSE tag was added to gene: MED12.
Fetal anomalies v2.10 LIFR Arina Puzriakova Tag to_be_confirmed_NHSE tag was added to gene: LIFR.
Fetal anomalies v2.10 FOXP4 Arina Puzriakova Tag Q2_21_rating was removed from gene: FOXP4.
Tag Q2_21_phenotype was removed from gene: FOXP4.
Tag Q2_21_expert_review was removed from gene: FOXP4.
Fetal anomalies v2.10 WNT7B Arina Puzriakova Tag Q3_22_rating was removed from gene: WNT7B.
Tag Q3_22_NHS_review was removed from gene: WNT7B.
Fetal anomalies v2.10 WBP11 Arina Puzriakova Tag Q2_21_rating was removed from gene: WBP11.
Fetal anomalies v2.10 TMEM70 Arina Puzriakova Tag Q3_22_rating was removed from gene: TMEM70.
Tag Q3_22_NHS_review was removed from gene: TMEM70.
Fetal anomalies v2.10 TMEM260 Arina Puzriakova Tag Q4_21_rating was removed from gene: TMEM260.
Fetal anomalies v2.10 TLL1 Arina Puzriakova Tag Q1_22_rating was removed from gene: TLL1.
Fetal anomalies v2.10 SYNE1 Arina Puzriakova Tag Q2_21_rating was removed from gene: SYNE1.
Fetal anomalies v2.10 SLC20A1 Arina Puzriakova Tag Q2_21_rating was removed from gene: SLC20A1.
Fetal anomalies v2.10 SLC12A6 Arina Puzriakova Tag for-review was removed from gene: SLC12A6.
Fetal anomalies v2.10 SETD2 Arina Puzriakova Tag Q3_22_rating was removed from gene: SETD2.
Tag Q3_22_NHS_review was removed from gene: SETD2.
Fetal anomalies v2.10 RAC3 Arina Puzriakova Tag Q2_22_rating was removed from gene: RAC3.
Fetal anomalies v2.10 PLD1 Arina Puzriakova Tag Q2_21_rating was removed from gene: PLD1.
Tag Q3_22_NHS_review was removed from gene: PLD1.
Fetal anomalies v2.10 PLCB4 Arina Puzriakova Tag Q2_22_rating was removed from gene: PLCB4.
Fetal anomalies v2.10 PEX6 Arina Puzriakova Tag Q1_22_MOI was removed from gene: PEX6.
Fetal anomalies v2.10 OTUD5 Arina Puzriakova Tag Q2_21_rating was removed from gene: OTUD5.
Fetal anomalies v2.10 NDUFB11 Arina Puzriakova Tag Q3_22_rating was removed from gene: NDUFB11.
Tag Q3_22_NHS_review was removed from gene: NDUFB11.
White matter disorders and cerebral calcification - narrow panel v2.9 ZFYVE26 Sarah Leigh Tag Q2_21_rating was removed from gene: ZFYVE26.
White matter disorders and cerebral calcification - narrow panel v2.9 WARS2 Sarah Leigh Tag Q2_21_rating was removed from gene: WARS2.
Fetal anomalies v2.10 MYH6 Arina Puzriakova Tag Q1_22_MOI was removed from gene: MYH6.
White matter disorders and cerebral calcification - narrow panel v2.9 VPS11 Sarah Leigh Tag Q2_21_rating was removed from gene: VPS11.
Fetal anomalies v2.10 MTM1 Arina Puzriakova Tag Q3_22_MOI was removed from gene: MTM1.
White matter disorders and cerebral calcification - narrow panel v2.9 UFM1 Sarah Leigh Tag Q2_21_rating was removed from gene: UFM1.
White matter disorders and cerebral calcification - narrow panel v2.9 TUFM Sarah Leigh Tag Q2_21_rating was removed from gene: TUFM.
White matter disorders and cerebral calcification - narrow panel v2.9 TMEM63A Sarah Leigh Tag Q2_21_rating was removed from gene: TMEM63A.
White matter disorders and cerebral calcification - narrow panel v2.9 SPG11 Sarah Leigh Tag Q2_21_rating was removed from gene: SPG11.
Fetal anomalies v2.10 MED13L Arina Puzriakova Tag Q3_22_rating was removed from gene: MED13L.
Tag Q3_22_NHS_review was removed from gene: MED13L.
White matter disorders and cerebral calcification - narrow panel v2.9 SPART Sarah Leigh Tag Q2_21_rating was removed from gene: SPART.
Fetal anomalies v2.10 LTBP3 Arina Puzriakova Tag Q1_22_MOI was removed from gene: LTBP3.
Fetal anomalies v2.10 LARS2 Arina Puzriakova Tag Q2_21_rating was removed from gene: LARS2.
White matter disorders and cerebral calcification - narrow panel v2.9 SNORD118 Sarah Leigh Tag Q2_21_rating was removed from gene: SNORD118.
Tag Q2_22_rating was removed from gene: SNORD118.
Tag Q2_22_NHS_review was removed from gene: SNORD118.
White matter disorders and cerebral calcification - narrow panel v2.9 SDHA Sarah Leigh Tag Q2_21_rating was removed from gene: SDHA.
Fetal anomalies v2.10 KIDINS220 Arina Puzriakova Tag to_be_confirmed_NHSE tag was added to gene: KIDINS220.
White matter disorders and cerebral calcification - narrow panel v2.9 RPIA Sarah Leigh Tag Q2_21_rating was removed from gene: RPIA.
White matter disorders and cerebral calcification - narrow panel v2.9 RNF220 Sarah Leigh Tag Q4_21_rating was removed from gene: RNF220.
Fetal anomalies v2.10 HSF4 Arina Puzriakova Tag Q1_22_MOI was removed from gene: HSF4.
Fetal anomalies v2.10 GRIN1 Arina Puzriakova Tag Q3_21_MOI was removed from gene: GRIN1.
White matter disorders and cerebral calcification - narrow panel v2.9 RAB11B Sarah Leigh Tag Q2_21_rating was removed from gene: RAB11B.
White matter disorders and cerebral calcification - narrow panel v2.9 PTEN Sarah Leigh Tag Q3_21_rating was removed from gene: PTEN.
White matter disorders and cerebral calcification - narrow panel v2.9 POLH Sarah Leigh Tag Q2_21_rating was removed from gene: POLH.
White matter disorders and cerebral calcification - narrow panel v2.9 POLH Sarah Leigh changed review comment from: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Red following NHS Genomic Medicine Service approval.
Fetal anomalies v2.10 FBN2 Arina Puzriakova Tag Q2_21_MOI was removed from gene: FBN2.
White matter disorders and cerebral calcification - narrow panel v2.9 PNPT1 Sarah Leigh Tag Q1_22_rating was removed from gene: PNPT1.
White matter disorders and cerebral calcification - narrow panel v2.9 PI4KA Sarah Leigh Tag Q3_21_rating was removed from gene: PI4KA.
Membranoproliferative glomerulonephritis including C3 glomerulopathy v2.31 CFHR5 Achchuthan Shanmugasundram Tag Q2_22_MOI was removed from gene: CFHR5.
Tag Q2_22_NHS_review was removed from gene: CFHR5.
White matter disorders and cerebral calcification - narrow panel v2.9 PEX6 Sarah Leigh Tag Q1_22_MOI was removed from gene: PEX6.
Membranoproliferative glomerulonephritis including C3 glomerulopathy v2.31 CFHR5 Achchuthan Shanmugasundram Classified gene: CFHR5 as Green List (high evidence)
Membranoproliferative glomerulonephritis including C3 glomerulopathy v2.31 CFHR5 Achchuthan Shanmugasundram Gene: cfhr5 has been classified as Green List (High Evidence).
White matter disorders and cerebral calcification - narrow panel v2.9 NFU1 Sarah Leigh Tag Q2_21_rating was removed from gene: NFU1.
White matter disorders and cerebral calcification - narrow panel v2.9 NAXE Sarah Leigh Tag Q2_21_rating was removed from gene: NAXE.
White matter disorders and cerebral calcification - narrow panel v2.9 NAXD Sarah Leigh Tag Q2_21_rating was removed from gene: NAXD.
White matter disorders and cerebral calcification - narrow panel v2.9 LIG3 Sarah Leigh Tag Q2_21_rating was removed from gene: LIG3.
White matter disorders and cerebral calcification - narrow panel v2.9 KIF5A Sarah Leigh Tag Q2_21_rating was removed from gene: KIF5A.
White matter disorders and cerebral calcification - narrow panel v2.9 KIAA1161 Sarah Leigh Tag Q2_21_rating was removed from gene: KIAA1161.
White matter disorders and cerebral calcification - narrow panel v2.9 ISCA2 Sarah Leigh Tag Q2_21_rating was removed from gene: ISCA2.
White matter disorders and cerebral calcification - narrow panel v2.9 ISCA1 Sarah Leigh Tag Q2_21_rating was removed from gene: ISCA1.
White matter disorders and cerebral calcification - narrow panel v2.9 HSPD1 Sarah Leigh Tag Q2_21_rating was removed from gene: HSPD1.
White matter disorders and cerebral calcification - narrow panel v2.9 HIKESHI Sarah Leigh Tag Q2_21_rating was removed from gene: HIKESHI.
Fetal anomalies v2.10 EHBP1L1 Arina Puzriakova Tag Q4_21_rating was removed from gene: EHBP1L1.
White matter disorders and cerebral calcification - narrow panel v2.9 GLRX5 Sarah Leigh Tag Q2_21_rating was removed from gene: GLRX5.
Fetal anomalies v2.10 EDNRB Arina Puzriakova Tag Q4_21_MOI was removed from gene: EDNRB.
Fetal anomalies v2.10 EDA Arina Puzriakova Tag Q3_22_rating was removed from gene: EDA.
Tag Q3_22_NHS_review was removed from gene: EDA.
White matter disorders and cerebral calcification - narrow panel v2.9 GLB1 Sarah Leigh Tag Q2_21_rating was removed from gene: GLB1.
Fetal anomalies v2.10 DPH1 Arina Puzriakova Tag Q2_21_rating was removed from gene: DPH1.
White matter disorders and cerebral calcification - narrow panel v2.9 FARSA Sarah Leigh Tag Q4_21_rating was removed from gene: FARSA.
White matter disorders and cerebral calcification - narrow panel v2.9 FA2H Sarah Leigh Tag Q2_21_rating was removed from gene: FA2H.
White matter disorders and cerebral calcification - narrow panel v2.9 ERCC5 Sarah Leigh Tag Q2_21_rating was removed from gene: ERCC5.
White matter disorders and cerebral calcification - narrow panel v2.9 ERCC4 Sarah Leigh Tag Q2_21_rating was removed from gene: ERCC4.
White matter disorders and cerebral calcification - narrow panel v2.9 ERCC3 Sarah Leigh Tag Q2_21_rating was removed from gene: ERCC3.
Fetal anomalies v2.10 DMPK Arina Puzriakova Tag Q3_21_MOI was removed from gene: DMPK.
Tag Q3_21_rating was removed from gene: DMPK.
Tag Q3_21_expert_review was removed from gene: DMPK.
White matter disorders and cerebral calcification - narrow panel v2.9 ERCC2 Sarah Leigh Tag Q2_21_rating was removed from gene: ERCC2.
White matter disorders and cerebral calcification - narrow panel v2.9 ERCC1 Sarah Leigh Tag Q3_21_rating was removed from gene: ERCC1.
White matter disorders and cerebral calcification - narrow panel v2.9 EPRS Sarah Leigh Tag Q2_21_rating was removed from gene: EPRS.
Fetal anomalies v2.10 CYP11B1 Arina Puzriakova Tag Q3_22_MOI was removed from gene: CYP11B1.
Fetal anomalies v2.10 CYP11A1 Arina Puzriakova Tag Q3_22_MOI was removed from gene: CYP11A1.
White matter disorders and cerebral calcification - narrow panel v2.9 ELOVL1 Sarah Leigh Tag Q4_21_rating was removed from gene: ELOVL1.
Fetal anomalies v2.10 CRYBB3 Arina Puzriakova Tag Q4_21_MOI was removed from gene: CRYBB3.
Fetal anomalies v2.10 COL6A3 Arina Puzriakova Tag Q4_21_MOI was removed from gene: COL6A3.
White matter disorders and cerebral calcification - narrow panel v2.9 DEGS1 Sarah Leigh Tag Q2_21_rating was removed from gene: DEGS1.
Fetal anomalies v2.10 COL6A1 Arina Puzriakova Tag Q4_21_MOI was removed from gene: COL6A1.
Fetal anomalies v2.10 COL1A2 Arina Puzriakova Tag Q3_22_MOI was removed from gene: COL1A2.
Tag Q3_22_expert_review was removed from gene: COL1A2.
White matter disorders and cerebral calcification - narrow panel v2.9 DCAF17 Sarah Leigh Tag Q2_21_rating was removed from gene: DCAF17.
Fetal anomalies v2.10 CLPB Arina Puzriakova Tag Q4_21_expert_review was removed from gene: CLPB.
Tag Q4_21_MOI was removed from gene: CLPB.
Fetal anomalies v2.10 CLCN7 Arina Puzriakova Tag Q4_21_MOI was removed from gene: CLCN7.
Fetal anomalies v2.10 BHLHA9 Arina Puzriakova Tag Q4_21_MOI was removed from gene: BHLHA9.
Fetal anomalies v2.10 ATAD3A Arina Puzriakova Tag Q3_21_MOI was removed from gene: ATAD3A.
White matter disorders and cerebral calcification - narrow panel v2.9 CSF1R Sarah Leigh Tag Q4_21_MOI was removed from gene: CSF1R.
Fetal anomalies v2.10 AP1S2 Arina Puzriakova Tag Q4_21_MOI was removed from gene: AP1S2.
White matter disorders and cerebral calcification - narrow panel v2.9 COLGALT1 Sarah Leigh Tag Q4_21_rating was removed from gene: COLGALT1.
White matter disorders and cerebral calcification - narrow panel v2.9 COA7 Sarah Leigh Tag Q2_21_rating was removed from gene: COA7.
White matter disorders and cerebral calcification - narrow panel v2.9 CNTNAP1 Sarah Leigh Tag Q2_21_rating was removed from gene: CNTNAP1.
Membranoproliferative glomerulonephritis including C3 glomerulopathy v2.30 CFHR5 Achchuthan Shanmugasundram commented on gene: CFHR5
White matter disorders and cerebral calcification - narrow panel v2.9 CLPP Sarah Leigh Tag Q3_21_rating was removed from gene: CLPP.
Membranoproliferative glomerulonephritis including C3 glomerulopathy v2.29 CFHR5 Achchuthan Shanmugasundram Source NHS GMS was added to CFHR5.
Mode of inheritance for gene CFHR5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rating Changed from Green List (high evidence) to Red List (low evidence)
White matter disorders and cerebral calcification - narrow panel v2.9 CLDN11 Sarah Leigh Tag Q2_21_rating was removed from gene: CLDN11.
White matter disorders and cerebral calcification - narrow panel v2.9 BOLA3 Sarah Leigh Tag Q2_21_rating was removed from gene: BOLA3.
White matter disorders and cerebral calcification - narrow panel v2.9 AUH Sarah Leigh Tag Q2_21_rating was removed from gene: AUH.
White matter disorders and cerebral calcification - narrow panel v2.9 APOPT1 Sarah Leigh Tag Q2_21_rating was removed from gene: APOPT1.
Cystic kidney disease v3.4 ZNF423 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: ZNF423.
Tag Q3_22_expert_review was removed from gene: ZNF423.
White matter disorders and cerebral calcification - narrow panel v2.9 AIFM1 Sarah Leigh Tag Q2_21_rating was removed from gene: AIFM1.
Cystic kidney disease v3.4 ZNF423 Achchuthan Shanmugasundram edited their review of gene: ZNF423: Changed rating: AMBER
Cystic kidney disease v3.4 ZNF423 Achchuthan Shanmugasundram changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Red.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber.
White matter disorders and cerebral calcification - narrow panel v2.9 ACOX1 Sarah Leigh Tag Q3_21_MOI was removed from gene: ACOX1.
White matter disorders and cerebral calcification - narrow panel v2.9 ACER3 Sarah Leigh Tag Q1_22_rating was removed from gene: ACER3.
White matter disorders and cerebral calcification - narrow panel v2.9 ACBD5 Sarah Leigh Tag Q2_21_rating was removed from gene: ACBD5.
White matter disorders and cerebral calcification - narrow panel v2.9 ABHD16A Sarah Leigh Tag Q4_21_rating was removed from gene: ABHD16A.
White matter disorders and cerebral calcification - narrow panel v2.9 AARS Sarah Leigh Tag Q2_21_rating was removed from gene: AARS.
White matter disorders and cerebral calcification - narrow panel v2.9 MPLKIP Sarah Leigh Tag Q2_21_rating was removed from gene: MPLKIP.
Tag Q2_21_expert_review was removed from gene: MPLKIP.
White matter disorders and cerebral calcification - narrow panel v2.9 GTF2H5 Sarah Leigh Tag Q2_21_rating was removed from gene: GTF2H5.
Tag Q2_21_expert_review was removed from gene: GTF2H5.
White matter disorders and cerebral calcification - narrow panel v2.9 CYP7B1 Sarah Leigh Tag Q3_22_rating was removed from gene: CYP7B1.
Tag Q3_22_expert_review was removed from gene: CYP7B1.
White matter disorders and cerebral calcification - narrow panel v2.9 BLOC1S1 Sarah Leigh Tag Q3_22_rating was removed from gene: BLOC1S1.
Cystic kidney disease v3.4 IFT140 Achchuthan Shanmugasundram Tag Q2_22_rating was removed from gene: IFT140.
Tag Q2_22_NHS_review was removed from gene: IFT140.
Cystic kidney disease v3.4 XPNPEP3 Achchuthan Shanmugasundram Tag Q2_21_expert_review was removed from gene: XPNPEP3.
Tag Q1_22_rating was removed from gene: XPNPEP3.
Tag Q1_22_phenotype was removed from gene: XPNPEP3.
Cystic kidney disease v3.4 PAX2 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: PAX2.
Tag Q3_22_NHS_review was removed from gene: PAX2.
Cystic kidney disease v3.4 GLA Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: GLA.
Tag Q3_22_NHS_review was removed from gene: GLA.
Fetal anomalies v2.10 DMPK_CTG Arina Puzriakova Tag Q3_21_rating was removed from STR: DMPK_CTG.
Tag Q3_21_expert_review was removed from STR: DMPK_CTG.
Fetal anomalies v2.10 DMPK_CTG Arina Puzriakova commented on STR: DMPK_CTG: After NHS Genomic Medicine Service consideration, the rating of this STR has not been changed and remains Amber.
Fetal anomalies v2.10 SCUBE3 Arina Puzriakova commented on gene: SCUBE3: The to_be_confirmed_NHSE tag has been added, as further NHSE review is required before promoting this gene to green.
Fetal anomalies v2.10 RAB11A Arina Puzriakova commented on gene: RAB11A
Fetal anomalies v2.10 MED12 Arina Puzriakova commented on gene: MED12
Fetal anomalies v2.10 LIFR Arina Puzriakova commented on gene: LIFR
Fetal anomalies v2.10 KIDINS220 Arina Puzriakova commented on gene: KIDINS220: The to_be_confirmed_NHSE tag has been added, as further NHSE review is required before promoting this gene to Green. However, the mode of inheritance of 'BIALLELIC, autosomal or pseudoautosomal' was approved following NHS Genomic Medicine Service consideration.
Fetal anomalies v2.10 FOXP4 Arina Puzriakova reviewed gene: FOXP4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v2.10 WNT7B Arina Puzriakova edited their review of gene: WNT7B: 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
Fetal anomalies v2.10 WBP11 Arina Puzriakova reviewed gene: WBP11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v2.10 TMEM70 Arina Puzriakova edited their review of gene: TMEM70: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Fetal anomalies v2.10 TMEM260 Arina Puzriakova reviewed gene: TMEM260: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v2.10 TLL1 Arina Puzriakova reviewed gene: TLL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v2.10 SYNE1 Arina Puzriakova commented on gene: SYNE1: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v2.10 SLC20A1 Arina Puzriakova edited their review of gene: SLC20A1: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Fetal anomalies v2.10 SLC12A6 Arina Puzriakova commented on gene: SLC12A6
Fetal anomalies v2.10 SETD2 Arina Puzriakova edited their review of gene: SETD2: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Fetal anomalies v2.10 RAC3 Arina Puzriakova edited their review of gene: RAC3: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Fetal anomalies v2.10 PLD1 Arina Puzriakova edited their review of gene: PLD1: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Fetal anomalies v2.10 PLCB4 Arina Puzriakova reviewed gene: PLCB4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v2.10 PEX6 Arina Puzriakova commented on gene: PEX6
Fetal anomalies v2.10 OTUD5 Arina Puzriakova commented on gene: OTUD5: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v2.10 NDUFB11 Arina Puzriakova edited their review of gene: NDUFB11: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Fetal anomalies v2.10 MYH6 Arina Puzriakova commented on gene: MYH6
Fetal anomalies v2.10 MTM1 Arina Puzriakova commented on gene: MTM1: The mode of inheritance of this gene has been updated to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' following NHS Genomic Medicine Service approval.
Fetal anomalies v2.10 MED13L Arina Puzriakova edited their review of gene: MED13L: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Fetal anomalies v2.10 LTBP3 Arina Puzriakova commented on gene: LTBP3
Fetal anomalies v2.10 LARS2 Arina Puzriakova commented on gene: LARS2: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v2.10 HSF4 Arina Puzriakova commented on gene: HSF4: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Fetal anomalies v2.10 GRIN1 Arina Puzriakova commented on gene: GRIN1
Fetal anomalies v2.10 FBN2 Arina Puzriakova commented on gene: FBN2
Fetal anomalies v2.10 EHBP1L1 Arina Puzriakova reviewed gene: EHBP1L1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v2.10 EDNRB Arina Puzriakova commented on gene: EDNRB
Fetal anomalies v2.10 EDA Arina Puzriakova edited their review of gene: EDA: Added comment: The rating of this gene has been updated to Red following NHS Genomic Medicine Service approval.; Changed rating: RED
Fetal anomalies v2.10 DPH1 Arina Puzriakova commented on gene: DPH1: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v2.10 DMPK Arina Puzriakova edited their review of gene: DMPK: Added comment: The rating of this gene has been updated to Red and the mode of inheritance set to 'Other' following NHS Genomic Medicine Service approval.; Changed rating: RED
Fetal anomalies v2.10 CYP11B1 Arina Puzriakova commented on gene: CYP11B1: The mode of inheritance of this gene has been updated to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Fetal anomalies v2.10 CYP11A1 Arina Puzriakova commented on gene: CYP11A1: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Fetal anomalies v2.10 CRYBB3 Arina Puzriakova commented on gene: CRYBB3: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Fetal anomalies v2.10 COL6A3 Arina Puzriakova commented on gene: COL6A3: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Fetal anomalies v2.10 COL6A1 Arina Puzriakova commented on gene: COL6A1: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Fetal anomalies v2.10 COL1A2 Arina Puzriakova commented on gene: COL1A2
Fetal anomalies v2.10 CLPB Arina Puzriakova commented on gene: CLPB: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Fetal anomalies v2.10 CLCN7 Arina Puzriakova commented on gene: CLCN7: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Fetal anomalies v2.10 BHLHA9 Arina Puzriakova commented on gene: BHLHA9
Fetal anomalies v2.10 ATAD3A Arina Puzriakova commented on gene: ATAD3A: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Fetal anomalies v2.10 AP1S2 Arina Puzriakova commented on gene: AP1S2: The mode of inheritance of this gene has been updated to 'X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)' following NHS Genomic Medicine Service approval.
White matter disorders and cerebral calcification - narrow panel v2.9 ZFYVE26 Sarah Leigh reviewed gene: ZFYVE26: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 WARS2 Sarah Leigh reviewed gene: WARS2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 VPS11 Sarah Leigh reviewed gene: VPS11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 UFM1 Sarah Leigh reviewed gene: UFM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 TUFM Sarah Leigh reviewed gene: TUFM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 TMEM63A Sarah Leigh reviewed gene: TMEM63A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 SPG11 Sarah Leigh reviewed gene: SPG11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 SPART Sarah Leigh reviewed gene: SPART: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 SNORD118 Sarah Leigh edited their review of gene: SNORD118: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
White matter disorders and cerebral calcification - narrow panel v2.9 SDHA Sarah Leigh reviewed gene: SDHA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 RPIA Sarah Leigh reviewed gene: RPIA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 RNF220 Sarah Leigh reviewed gene: RNF220: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 RAB11B Sarah Leigh reviewed gene: RAB11B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 PTEN Sarah Leigh reviewed gene: PTEN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 POLH Sarah Leigh reviewed gene: POLH: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 PNPT1 Sarah Leigh reviewed gene: PNPT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 PI4KA Sarah Leigh reviewed gene: PI4KA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 PEX6 Sarah Leigh commented on gene: PEX6: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
White matter disorders and cerebral calcification - narrow panel v2.9 NFU1 Sarah Leigh reviewed gene: NFU1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 NAXE Sarah Leigh reviewed gene: NAXE: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 NAXD Sarah Leigh reviewed gene: NAXD: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 LIG3 Sarah Leigh reviewed gene: LIG3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 KIF5A Sarah Leigh reviewed gene: KIF5A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 KIAA1161 Sarah Leigh reviewed gene: KIAA1161: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 ISCA2 Sarah Leigh reviewed gene: ISCA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 ISCA1 Sarah Leigh reviewed gene: ISCA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 HSPD1 Sarah Leigh reviewed gene: HSPD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 HIKESHI Sarah Leigh reviewed gene: HIKESHI: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 GLRX5 Sarah Leigh reviewed gene: GLRX5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 GLB1 Sarah Leigh reviewed gene: GLB1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 FARSA Sarah Leigh reviewed gene: FARSA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 FA2H Sarah Leigh commented on gene: FA2H: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
White matter disorders and cerebral calcification - narrow panel v2.9 ERCC5 Sarah Leigh reviewed gene: ERCC5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 ERCC4 Sarah Leigh reviewed gene: ERCC4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 ERCC3 Sarah Leigh reviewed gene: ERCC3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 ERCC2 Sarah Leigh reviewed gene: ERCC2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 ERCC1 Sarah Leigh reviewed gene: ERCC1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 EPRS Sarah Leigh reviewed gene: EPRS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 ELOVL1 Sarah Leigh reviewed gene: ELOVL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 DEGS1 Sarah Leigh reviewed gene: DEGS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 DCAF17 Sarah Leigh reviewed gene: DCAF17: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 CSF1R Sarah Leigh reviewed gene: CSF1R: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 COLGALT1 Sarah Leigh reviewed gene: COLGALT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 COA7 Sarah Leigh commented on gene: COA7: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
White matter disorders and cerebral calcification - narrow panel v2.9 CNTNAP1 Sarah Leigh reviewed gene: CNTNAP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 CLPP Sarah Leigh reviewed gene: CLPP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 CLDN11 Sarah Leigh commented on gene: CLDN11: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
White matter disorders and cerebral calcification - narrow panel v2.9 BOLA3 Sarah Leigh reviewed gene: BOLA3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 AUH Sarah Leigh reviewed gene: AUH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 APOPT1 Sarah Leigh reviewed gene: APOPT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 AIFM1 Sarah Leigh reviewed gene: AIFM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 ACOX1 Sarah Leigh reviewed gene: ACOX1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 ACER3 Sarah Leigh reviewed gene: ACER3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 ACBD5 Sarah Leigh reviewed gene: ACBD5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 ABHD16A Sarah Leigh reviewed gene: ABHD16A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 AARS Sarah Leigh reviewed gene: AARS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 MPLKIP Sarah Leigh reviewed gene: MPLKIP: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 GTF2H5 Sarah Leigh reviewed gene: GTF2H5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 CYP7B1 Sarah Leigh reviewed gene: CYP7B1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v2.9 BLOC1S1 Sarah Leigh reviewed gene: BLOC1S1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Cystic kidney disease v3.4 ZNF423 Achchuthan Shanmugasundram reviewed gene: ZNF423: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Cystic kidney disease v3.4 IFT140 Achchuthan Shanmugasundram reviewed gene: IFT140: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Cystic kidney disease v3.4 XPNPEP3 Achchuthan Shanmugasundram reviewed gene: XPNPEP3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Cystic kidney disease v3.4 PAX2 Achchuthan Shanmugasundram reviewed gene: PAX2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Cystic kidney disease v3.4 GLA Achchuthan Shanmugasundram reviewed gene: GLA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Cystic kidney disease v3.3 XPNPEP3 Achchuthan Shanmugasundram Source Expert Review Green was added to XPNPEP3.
Source NHS GMS was added to XPNPEP3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cystic kidney disease v3.3 PAX2 Achchuthan Shanmugasundram Source Expert Review Green was added to PAX2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cystic kidney disease v3.3 IFT140 Achchuthan Shanmugasundram Source Expert Review Green was added to IFT140.
Source NHS GMS was added to IFT140.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cystic kidney disease v3.3 GLA Achchuthan Shanmugasundram Source Expert Review Green was added to GLA.
Source NHS GMS was added to GLA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v2.9 WNT7B Arina Puzriakova Source Expert Review Green was added to WNT7B.
Source NHS GMS was added to WNT7B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v2.9 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)
Fetal anomalies v2.9 TMEM70 Arina Puzriakova Source Expert Review Green was added to TMEM70.
Source NHS GMS was added to TMEM70.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v2.9 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)
Fetal anomalies v2.9 TLL1 Arina Puzriakova Source Expert Review Green was added to TLL1.
Source NHS GMS was added to TLL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v2.9 SYNE1 Arina Puzriakova Source Expert Review Green was added to SYNE1.
Source NHS GMS was added to SYNE1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v2.9 SLC20A1 Arina Puzriakova Source Expert Review Green was added to SLC20A1.
Source NHS GMS was added to SLC20A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v2.9 SLC12A6 Arina Puzriakova Source NHS GMS was added to SLC12A6.
Mode of inheritance for gene SLC12A6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Atypical haemolytic uraemic syndrome v2.17 CFI Achchuthan Shanmugasundram Tag Q2_22_MOI was removed from gene: CFI.
Fetal anomalies v2.9 SETD2 Arina Puzriakova Source Expert Review Green was added to SETD2.
Source NHS GMS was added to SETD2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v2.9 RAC3 Arina Puzriakova Source Expert Review Green was added to RAC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v2.9 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)
Fetal anomalies v2.9 PLCB4 Arina Puzriakova Source Expert Review Green was added to PLCB4.
Source NHS GMS was added to PLCB4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v2.9 PEX6 Arina Puzriakova Source NHS GMS was added to PEX6.
Mode of inheritance for gene PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v2.9 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)
Fetal anomalies v2.9 NDUFB11 Arina Puzriakova Source Expert Review Green was added to NDUFB11.
Source NHS GMS was added to NDUFB11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v2.9 MYH6 Arina Puzriakova Source NHS GMS was added to MYH6.
Mode of inheritance for gene MYH6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v2.9 MTM1 Arina Puzriakova Source NHS GMS was added to MTM1.
Mode of inheritance for gene MTM1 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Fetal anomalies v2.9 MED13L Arina Puzriakova Source Expert Review Green was added to MED13L.
Source NHS GMS was added to MED13L.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v2.9 LTBP3 Arina Puzriakova Source NHS GMS was added to LTBP3.
Mode of inheritance for gene LTBP3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v2.9 LARS2 Arina Puzriakova Source Expert Review Green was added to LARS2.
Source NHS GMS was added to LARS2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v2.9 KIDINS220 Arina Puzriakova Source NHS GMS was added to KIDINS220.
Fetal anomalies v2.9 HSF4 Arina Puzriakova Source NHS GMS was added to HSF4.
Mode of inheritance for gene HSF4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v2.9 GRIN1 Arina Puzriakova Source NHS GMS was added to GRIN1.
Mode of inheritance for gene GRIN1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Fetal anomalies v2.9 FBN2 Arina Puzriakova Source NHS GMS was added to FBN2.
Mode of inheritance for gene FBN2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v2.9 EHBP1L1 Arina Puzriakova Source Expert Review Green was added to EHBP1L1.
Source NHS GMS was added to EHBP1L1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v2.9 EDNRB Arina Puzriakova Source NHS GMS was added to EDNRB.
Mode of inheritance for gene EDNRB was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v2.9 EDA Arina Puzriakova Source Expert Review Red was added to EDA.
Source NHS GMS was added to EDA.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Fetal anomalies v2.9 DPH1 Arina Puzriakova Source Expert Review Green was added to DPH1.
Source NHS GMS was added to DPH1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v2.9 DMPK Arina Puzriakova Source Expert Review Red was added to DMPK.
Source NHS GMS was added to DMPK.
Mode of inheritance for gene DMPK was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other
Rating Changed from Green List (high evidence) to Red List (low evidence)
Fetal anomalies v2.9 CYP11B1 Arina Puzriakova Source NHS GMS was added to CYP11B1.
Mode of inheritance for gene CYP11B1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v2.9 CYP11A1 Arina Puzriakova Source NHS GMS was added to CYP11A1.
Mode of inheritance for gene CYP11A1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v2.9 CRYBB3 Arina Puzriakova Source NHS GMS was added to CRYBB3.
Mode of inheritance for gene CRYBB3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v2.9 COL6A3 Arina Puzriakova Source NHS GMS was added to COL6A3.
Mode of inheritance for gene COL6A3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v2.9 COL6A1 Arina Puzriakova Source NHS GMS was added to COL6A1.
Mode of inheritance for gene COL6A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v2.9 COL1A2 Arina Puzriakova Source NHS GMS was added to COL1A2.
Mode of inheritance for gene COL1A2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v2.9 CLPB Arina Puzriakova Source NHS GMS was added to CLPB.
Mode of inheritance for gene CLPB was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v2.9 CLCN7 Arina Puzriakova Source NHS GMS was added to CLCN7.
Mode of inheritance for gene CLCN7 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v2.9 BHLHA9 Arina Puzriakova Source NHS GMS was added to BHLHA9.
Mode of inheritance for gene BHLHA9 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v2.9 ATAD3A Arina Puzriakova Source NHS GMS was added to ATAD3A.
Mode of inheritance for gene ATAD3A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v2.9 AP1S2 Arina Puzriakova Source NHS GMS was added to AP1S2.
Mode of inheritance for gene AP1S2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
White matter disorders and cerebral calcification - narrow panel v2.8 ZFYVE26 Sarah Leigh Source NHS GMS was added to ZFYVE26.
Source Expert Review Green was added to ZFYVE26.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 WARS2 Sarah Leigh Source NHS GMS was added to WARS2.
Source Expert Review Green was added to WARS2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 VPS11 Sarah Leigh Source NHS GMS was added to VPS11.
Source Expert Review Green was added to VPS11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 UFM1 Sarah Leigh Source NHS GMS was added to UFM1.
Source Expert Review Green was added to UFM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 TUFM Sarah Leigh Source NHS GMS was added to TUFM.
Source Expert Review Green was added to TUFM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 TMEM63A Sarah Leigh Source NHS GMS was added to TMEM63A.
Source Expert Review Green was added to TMEM63A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 SPG11 Sarah Leigh Source NHS GMS was added to SPG11.
Source Expert Review Green was added to SPG11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 SPART Sarah Leigh Source NHS GMS was added to SPART.
Source Expert Review Green was added to SPART.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 SNORD118 Sarah Leigh Source NHS GMS was added to SNORD118.
Source Expert Review Green was added to SNORD118.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 SDHA Sarah Leigh Source NHS GMS was added to SDHA.
Source Expert Review Green was added to SDHA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 RPIA Sarah Leigh Source NHS GMS was added to RPIA.
Source Expert Review Green was added to RPIA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 RNF220 Sarah Leigh Source NHS GMS was added to RNF220.
Source Expert Review Green was added to RNF220.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 RAB11B Sarah Leigh Source NHS GMS was added to RAB11B.
Source Expert Review Green was added to RAB11B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 PTEN Sarah Leigh Source NHS GMS was added to PTEN.
Source Expert Review Green was added to PTEN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 POLH Sarah Leigh Source NHS GMS was added to POLH.
Source Expert Review Red was added to POLH.
Rating Changed from Green List (high evidence) to Red List (low evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 PNPT1 Sarah Leigh Source NHS GMS was added to PNPT1.
Source Expert Review Green was added to PNPT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 PI4KA Sarah Leigh Source NHS GMS was added to PI4KA.
Source Expert Review Green was added to PI4KA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 PEX6 Sarah Leigh Source NHS GMS was added to PEX6.
Mode of inheritance for gene PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v2.8 NFU1 Sarah Leigh Source NHS GMS was added to NFU1.
Source Expert Review Green was added to NFU1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 NAXE Sarah Leigh Source NHS GMS was added to NAXE.
Source Expert Review Green was added to NAXE.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 NAXD Sarah Leigh Source NHS GMS was added to NAXD.
Source Expert Review Green was added to NAXD.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 MPLKIP Sarah Leigh Source NHS GMS was added to MPLKIP.
Source Expert Review Red was added to MPLKIP.
Rating Changed from Green List (high evidence) to Red List (low evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 LIG3 Sarah Leigh Source NHS GMS was added to LIG3.
Source Expert Review Green was added to LIG3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 KIF5A Sarah Leigh Source NHS GMS was added to KIF5A.
Source Expert Review Green was added to KIF5A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 KIAA1161 Sarah Leigh Source NHS GMS was added to KIAA1161.
Source Expert Review Green was added to KIAA1161.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 ISCA2 Sarah Leigh Source NHS GMS was added to ISCA2.
Source Expert Review Green was added to ISCA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 ISCA1 Sarah Leigh Source NHS GMS was added to ISCA1.
Source Expert Review Green was added to ISCA1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 HSPD1 Sarah Leigh Source NHS GMS was added to HSPD1.
Source Expert Review Green was added to HSPD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 HIKESHI Sarah Leigh Source NHS GMS was added to HIKESHI.
Source Expert Review Green was added to HIKESHI.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 GTF2H5 Sarah Leigh Source Expert Review Amber was added to GTF2H5.
Source NHS GMS was added to GTF2H5.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 GLRX5 Sarah Leigh Source NHS GMS was added to GLRX5.
Source Expert Review Green was added to GLRX5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 GLB1 Sarah Leigh Source NHS GMS was added to GLB1.
Source Expert Review Green was added to GLB1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 FARSA Sarah Leigh Source NHS GMS was added to FARSA.
Source Expert Review Green was added to FARSA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 FA2H Sarah Leigh Source NHS GMS was added to FA2H.
Source Expert Review Green was added to FA2H.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 ERCC5 Sarah Leigh Source Expert Review Amber was added to ERCC5.
Source NHS GMS was added to ERCC5.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 ERCC4 Sarah Leigh Source Expert Review Amber was added to ERCC4.
Source NHS GMS was added to ERCC4.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 ERCC3 Sarah Leigh Source NHS GMS was added to ERCC3.
Source Expert Review Red was added to ERCC3.
Rating Changed from Green List (high evidence) to Red List (low evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 ERCC2 Sarah Leigh Source Expert Review Amber was added to ERCC2.
Source NHS GMS was added to ERCC2.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 ERCC1 Sarah Leigh Source Expert Review Amber was added to ERCC1.
Source NHS GMS was added to ERCC1.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 EPRS Sarah Leigh Source NHS GMS was added to EPRS.
Source Expert Review Green was added to EPRS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 ELOVL1 Sarah Leigh Source NHS GMS was added to ELOVL1.
Source Expert Review Green was added to ELOVL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 DEGS1 Sarah Leigh Source NHS GMS was added to DEGS1.
Source Expert Review Green was added to DEGS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 DCAF17 Sarah Leigh Source NHS GMS was added to DCAF17.
Source Expert Review Green was added to DCAF17.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 CYP7B1 Sarah Leigh Source NHS GMS was added to CYP7B1.
Source Expert Review Green was added to CYP7B1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 CSF1R Sarah Leigh Source NHS GMS was added to CSF1R.
Mode of inheritance for gene CSF1R was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v2.8 COLGALT1 Sarah Leigh Source NHS GMS was added to COLGALT1.
Source Expert Review Green was added to COLGALT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 COA7 Sarah Leigh Source NHS GMS was added to COA7.
Source Expert Review Green was added to COA7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 CNTNAP1 Sarah Leigh Source NHS GMS was added to CNTNAP1.
Source Expert Review Green was added to CNTNAP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 CLPP Sarah Leigh Source NHS GMS was added to CLPP.
Source Expert Review Green was added to CLPP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 CLDN11 Sarah Leigh Source NHS GMS was added to CLDN11.
Source Expert Review Green was added to CLDN11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 BOLA3 Sarah Leigh Source NHS GMS was added to BOLA3.
Source Expert Review Green was added to BOLA3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 BLOC1S1 Sarah Leigh Source NHS GMS was added to BLOC1S1.
Source Expert Review Green was added to BLOC1S1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 AUH Sarah Leigh Source NHS GMS was added to AUH.
Source Expert Review Green was added to AUH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 APOPT1 Sarah Leigh Source NHS GMS was added to APOPT1.
Source Expert Review Green was added to APOPT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 AIFM1 Sarah Leigh Source NHS GMS was added to AIFM1.
Source Expert Review Green was added to AIFM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 ACOX1 Sarah Leigh Source NHS GMS was added to ACOX1.
Mode of inheritance for gene ACOX1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v2.8 ACER3 Sarah Leigh Source NHS GMS was added to ACER3.
Source Expert Review Green was added to ACER3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 ACBD5 Sarah Leigh Source NHS GMS was added to ACBD5.
Source Expert Review Green was added to ACBD5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 ABHD16A Sarah Leigh Source NHS GMS was added to ABHD16A.
Source Expert Review Green was added to ABHD16A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v2.8 AARS Sarah Leigh Source NHS GMS was added to AARS.
Source Expert Review Green was added to AARS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Familial hypercholesterolaemia (GMS) v1.12 APOE Arina Puzriakova Tag Q1_22_MOI was removed from gene: APOE.
Familial hypercholesterolaemia (GMS) v1.12 APOE Arina Puzriakova commented on gene: APOE
Familial hypercholesterolaemia (GMS) v1.11 APOE Arina Puzriakova Source NHS GMS was added to APOE.
Mode of inheritance for gene APOE was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Renal ciliopathies v2.4 ZNF423 Sarah Leigh Tag Q3_22_rating was removed from gene: ZNF423.
Tag Q3_22_expert_review was removed from gene: ZNF423.
Renal ciliopathies v2.4 XPNPEP3 Sarah Leigh Tag Q1_22_rating was removed from gene: XPNPEP3.
Renal ciliopathies v2.4 XPNPEP3 Sarah Leigh Source Expert Review Green was added to XPNPEP3.
Source NHS GMS was added to XPNPEP3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Atypical haemolytic uraemic syndrome v2.17 CFI Achchuthan Shanmugasundram commented on gene: CFI
Atypical haemolytic uraemic syndrome v2.16 CFI Achchuthan Shanmugasundram Mode of inheritance for gene CFI was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cerebral vascular malformations v2.68 SETD5 Eleanor Williams Tag to_be_confirmed_NHSE tag was added to gene: SETD5.
Structural eye disease v2.3 WLS Achchuthan Shanmugasundram Tag Q1_22_NHS_review was removed from gene: WLS.
Tag Q2_22_rating was removed from gene: WLS.
Cerebral vascular malformations v2.68 CNOT3 Eleanor Williams Tag to_be_confirmed_NHSE tag was added to gene: CNOT3.
Structural eye disease v2.3 TMEM5 Achchuthan Shanmugasundram Tag Q2_22_rating was removed from gene: TMEM5.
Tag Q2_22_NHS_review was removed from gene: TMEM5.
Cerebral vascular malformations v2.68 CHD4 Eleanor Williams Tag to_be_confirmed_NHSE tag was added to gene: CHD4.
Renal ciliopathies v2.3 XPNPEP3 Sarah Leigh changed review comment from: The rating of this gene has been updated to XX following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Structural eye disease v2.3 PACS1 Achchuthan Shanmugasundram Tag Q2_22_rating was removed from gene: PACS1.
Tag Q2_22_NHS_review was removed from gene: PACS1.
Cerebral vascular malformations v2.68 CBL Eleanor Williams Tag Q3_21_rating was removed from gene: CBL.
Cerebral vascular malformations v2.68 ANGPTL6 Eleanor Williams Tag Q2_21_rating was removed from gene: ANGPTL6.
Cerebral vascular malformations v2.68 ANGPTL6 Eleanor Williams changed review comment from: The rating of this gene has been updated to greenfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Structural eye disease v2.3 HHAT Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: HHAT.
Tag Q1_22_NHS_review was removed from gene: HHAT.
Cerebral vascular malformations v2.68 SETD5 Eleanor Williams commented on gene: SETD5: The to_be_confirmed_NHSE tag has been added, as further NHSE review is required before promoting this gene to green.
Cerebral vascular malformations v2.68 CNOT3 Eleanor Williams commented on gene: CNOT3: The to_be_confirmed_NHSE tag has been added, as further NHSE review is required before promoting this gene to green.
Cerebral vascular malformations v2.68 CHD4 Eleanor Williams commented on gene: CHD4: The to_be_confirmed_NHSE tag has been added, as further NHSE review is required before promoting this gene to green.
Cerebral vascular malformations v2.68 CBL Eleanor Williams commented on gene: CBL
Cerebral vascular malformations v2.68 ANGPTL6 Eleanor Williams reviewed gene: ANGPTL6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Cerebral vascular malformations v2.67 ANGPTL6 Eleanor Williams Source Expert Review Green was added to ANGPTL6.
Source NHS GMS was added to ANGPTL6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v2.3 GJA1 Achchuthan Shanmugasundram Tag Q3_21_MOI was removed from gene: GJA1.
Structural eye disease v2.3 CRIM1 Achchuthan Shanmugasundram Tag Q2_21_NHS_review was removed from gene: CRIM1.
Tag Q2_22_rating was removed from gene: CRIM1.
Structural eye disease v2.3 WLS Achchuthan Shanmugasundram reviewed gene: WLS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Structural eye disease v2.3 TMEM5 Achchuthan Shanmugasundram reviewed gene: TMEM5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Structural eye disease v2.3 PACS1 Achchuthan Shanmugasundram reviewed gene: PACS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Structural eye disease v2.3 HHAT Achchuthan Shanmugasundram reviewed gene: HHAT: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Structural eye disease v2.3 GJA1 Achchuthan Shanmugasundram reviewed gene: GJA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Structural eye disease v2.3 CRIM1 Achchuthan Shanmugasundram reviewed gene: CRIM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Structural eye disease v2.2 WLS Achchuthan Shanmugasundram Source Expert Review Green was added to WLS.
Source NHS GMS was added to WLS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v2.2 TMEM5 Achchuthan Shanmugasundram Source Expert Review Green was added to TMEM5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v2.2 PACS1 Achchuthan Shanmugasundram Source Expert Review Green was added to PACS1.
Source NHS GMS was added to PACS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v2.2 HHAT Achchuthan Shanmugasundram Source Expert Review Green was added to HHAT.
Source NHS GMS was added to HHAT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v2.2 GJA1 Achchuthan Shanmugasundram Mode of inheritance for gene GJA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v2.2 CRIM1 Achchuthan Shanmugasundram Source Expert Review Green was added to CRIM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tubulointerstitial kidney disease v2.4 TTC21B Sarah Leigh Tag Q2_22_MOI was removed from gene: TTC21B.
Tag Q2_22_expert_review was removed from gene: TTC21B.
Stickler syndrome v3.3 VCAN Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: VCAN.
Tag Q3_22_NHS_review was removed from gene: VCAN.
Tag Q3_22_expert_review was removed from gene: VCAN.
Stickler syndrome v3.3 BMP4 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: BMP4.
Tag Q3_22_NHS_review was removed from gene: BMP4.
Stickler syndrome v3.3 VCAN Achchuthan Shanmugasundram reviewed gene: VCAN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Stickler syndrome v3.3 BMP4 Achchuthan Shanmugasundram reviewed gene: BMP4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Stickler syndrome v3.2 VCAN Achchuthan Shanmugasundram Source Expert Review Green was added to VCAN.
Source NHS GMS was added to VCAN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Stickler syndrome v3.2 BMP4 Achchuthan Shanmugasundram Source Expert Review Green was added to BMP4.
Source NHS GMS was added to BMP4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v3.26 COL9A3 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE tag was added to gene: COL9A3.
Retinal disorders v3.26 COL9A2 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE tag was added to gene: COL9A2.
Retinal disorders v3.26 COL9A1 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE tag was added to gene: COL9A1.
Retinal disorders v3.26 COL11A1 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE tag was added to gene: COL11A1.
Retinal disorders v3.26 IRX6 Achchuthan Shanmugasundram Tag Q3_21_rating was removed from gene: IRX6.
Tag Q3_21_expert_review was removed from gene: IRX6.
Retinal disorders v3.26 IRX6 Achchuthan Shanmugasundram changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Red.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Red. GMS reviewers note that it should not be added as gene for SNV calling, but a region for CNV duplication testing would be appropriate, as per Eleanor Williams comment on PanelApp.
Arthrogryposis v4.5 CNTN1 Eleanor Williams commented on gene: CNTN1
Tubulointerstitial kidney disease v2.4 XPNPEP3 Sarah Leigh commented on gene: XPNPEP3: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Tubulointerstitial kidney disease v2.4 TTC21B Sarah Leigh commented on gene: TTC21B
Retinal disorders v3.26 IRX5 Achchuthan Shanmugasundram Tag Q3_21_rating was removed from gene: IRX5.
Tag Q3_21_expert_review was removed from gene: IRX5.
Arthrogryposis v4.5 CNTN1 Eleanor Williams Tag Q3_21_NHS_review was removed from gene: CNTN1.
Tubulointerstitial kidney disease v2.3 XPNPEP3 Sarah Leigh Source Expert Review Green was added to XPNPEP3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tubulointerstitial kidney disease v2.3 TTC21B Sarah Leigh Mode of inheritance for gene TTC21B was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v3.26 IRX5 Achchuthan Shanmugasundram changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Red. The GMS reviewers wonder whether this could be added as a region instead.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Red. The GMS reviewers note that it should not be added as gene for SNV calling, but a region for CNV duplication testing would be appropriate, as per Eleanor Williams comment on PanelApp.
Arthrogryposis v4.5 PEX6 Eleanor Williams Tag Q1_22_MOI was removed from gene: PEX6.
Retinal disorders v3.26 IRX5 Achchuthan Shanmugasundram changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Red.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Red. The GMS reviewers wonder whether this could be added as a region instead.
Arthrogryposis v4.5 COL6A1 Eleanor Williams Tag Q4_21_MOI was removed from gene: COL6A1.
Arthrogryposis v4.5 ACTA1 Eleanor Williams Tag Q3_21_MOI was removed from gene: ACTA1.
Arthrogryposis v4.5 ADAMTS15 Eleanor Williams Tag Q3_22_rating was removed from gene: ADAMTS15.
Tag Q3_22_MOI was removed from gene: ADAMTS15.
Arthrogryposis v4.5 ADAMTS15 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set toBIALLELIC, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.; to: 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.
Retinal disorders v3.26 PRPF6 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: PRPF6.
Tag Q3_22_expert_review was removed from gene: PRPF6.
Arthrogryposis v4.5 PEX6 Eleanor Williams commented on gene: PEX6
Arthrogryposis v4.5 COL6A1 Eleanor Williams commented on gene: COL6A1
Arthrogryposis v4.5 ACTA1 Eleanor Williams commented on gene: ACTA1
Arthrogryposis v4.5 ADAMTS15 Eleanor Williams reviewed gene: ADAMTS15: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Arthrogryposis v4.4 PEX6 Eleanor Williams Source NHS GMS was added to PEX6.
Mode of inheritance for gene PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Arthrogryposis v4.4 COL6A1 Eleanor Williams Source NHS GMS was added to COL6A1.
Mode of inheritance for gene COL6A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Arthrogryposis v4.4 ADAMTS15 Eleanor Williams Source Expert Review Green was added to ADAMTS15.
Source NHS GMS was added to ADAMTS15.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Arthrogryposis v4.4 ACTA1 Eleanor Williams Source NHS GMS was added to ACTA1.
Mode of inheritance for gene ACTA1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Retinal disorders v3.26 STN1 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: STN1.
Retinal disorders v3.26 SSBP1 Achchuthan Shanmugasundram Tag Q1_22_MOI was removed from gene: SSBP1.
Retinal disorders v3.26 RNU4ATAC Achchuthan Shanmugasundram Tag Q2_22_rating was removed from gene: RNU4ATAC.
Tag Q2_22_NHS_review was removed from gene: RNU4ATAC.
Retinal disorders v3.26 PEX6 Achchuthan Shanmugasundram Tag Q1_22_MOI was removed from gene: PEX6.
Retinal disorders v3.26 ARSG Achchuthan Shanmugasundram Tag Q2_22_rating was removed from gene: ARSG.
Tag Q2_22_NHS_review was removed from gene: ARSG.
Retinal disorders v3.26 AFG3L2 Achchuthan Shanmugasundram Tag Q2_22_MOI was removed from gene: AFG3L2.
Retinal disorders v3.26 ACO2 Achchuthan Shanmugasundram Tag Q2_22_MOI was removed from gene: ACO2.
Retinal disorders v3.26 RGR Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: RGR.
Tag Q3_22_NHS_review was removed from gene: RGR.
Retinal disorders v3.26 POMT1 Achchuthan Shanmugasundram Tag Q3_21_NHS_review was removed from gene: POMT1.
Tag Q3_22_rating was removed from gene: POMT1.
Albinism or congenital nystagmus v2.3 SETX Sarah Leigh Tag Q2_22_MOI was removed from gene: SETX.
Thoracic aortic aneurysm or dissection (GMS) v2.3 THSD4 Arina Puzriakova Tag Q2_21_rating was removed from gene: THSD4.
Thoracic aortic aneurysm or dissection (GMS) v2.3 LTBP3 Arina Puzriakova Tag Q1_22_rating was removed from gene: LTBP3.
Thoracic aortic aneurysm or dissection (GMS) v2.3 ARIH1 Arina Puzriakova Tag Q3_21_rating was removed from gene: ARIH1.
Thoracic aortic aneurysm or dissection (GMS) v2.3 IPO8 Arina Puzriakova Tag Q2_21_rating was removed from gene: IPO8.
Thoracic aortic aneurysm or dissection (GMS) v2.3 ASPH Arina Puzriakova Tag Q3_22_rating was removed from gene: ASPH.
Tag Q3_22_MOI was removed from gene: ASPH.
Tag Q3_22_NHS_review was removed from gene: ASPH.
Albinism or congenital nystagmus v2.3 SETX Sarah Leigh commented on gene: SETX: The mode of inheritance of this gene has been updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Albinism or congenital nystagmus v2.2 SETX Sarah Leigh Source NHS GMS was added to SETX.
Mode of inheritance for gene SETX was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Thoracic aortic aneurysm or dissection (GMS) v2.3 THSD4 Arina Puzriakova reviewed gene: THSD4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Thoracic aortic aneurysm or dissection (GMS) v2.3 LTBP3 Arina Puzriakova reviewed gene: LTBP3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Thoracic aortic aneurysm or dissection (GMS) v2.3 ARIH1 Arina Puzriakova reviewed gene: ARIH1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Thoracic aortic aneurysm or dissection (GMS) v2.3 IPO8 Arina Puzriakova reviewed gene: IPO8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Thoracic aortic aneurysm or dissection (GMS) v2.3 ASPH Arina Puzriakova reviewed gene: ASPH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Thoracic aortic aneurysm or dissection (GMS) v2.2 IPO8 Arina Puzriakova Source Expert Review Green was added to IPO8.
Source NHS GMS was added to IPO8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Thoracic aortic aneurysm or dissection (GMS) v2.2 ASPH Arina Puzriakova Source Expert Review Green was added to ASPH.
Source NHS GMS was added to ASPH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary lymphoedema v3.2 PIEZO1 Arina Puzriakova Tag Q4_21_MOI was removed from gene: PIEZO1.
Primary lymphoedema v3.2 PIEZO1 Arina Puzriakova commented on gene: PIEZO1: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed and remains 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'.
Hypertrophic cardiomyopathy v3.3 ALPK3 Arina Puzriakova Tag Q2_22_rating was removed from gene: ALPK3.
Hypertrophic cardiomyopathy v3.3 JPH2 Arina Puzriakova Tag Q3_22_rating was removed from gene: JPH2.
Tag Q3_22_expert_review was removed from gene: JPH2.
Hypertrophic cardiomyopathy v3.3 ALPK3 Arina Puzriakova reviewed gene: ALPK3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hypertrophic cardiomyopathy v3.3 JPH2 Arina Puzriakova reviewed gene: JPH2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hypertrophic cardiomyopathy v3.2 ALPK3 Arina Puzriakova Source Expert Review Green was added to ALPK3.
Source NHS GMS was added to ALPK3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hypertrophic cardiomyopathy v3.2 JPH2 Arina Puzriakova Source NHS GMS was added to JPH2.
Source Expert Review Amber was added to JPH2.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Dilated and arrhythmogenic cardiomyopathy v2.4 TBX5 Arina Puzriakova Tag Q2_21_rating was removed from gene: TBX5.
Dilated and arrhythmogenic cardiomyopathy v2.4 SPEG Arina Puzriakova Tag Q2_21_rating was removed from gene: SPEG.
Dilated and arrhythmogenic cardiomyopathy v2.4 RPL3L Arina Puzriakova Tag Q2_21_rating was removed from gene: RPL3L.
Dilated and arrhythmogenic cardiomyopathy v2.4 NRAP Arina Puzriakova Tag Q2_21_rating was removed from gene: NRAP.
Dilated and arrhythmogenic cardiomyopathy v2.4 MYLK3 Arina Puzriakova Tag Q2_21_rating was removed from gene: MYLK3.
Dilated and arrhythmogenic cardiomyopathy v2.4 FLII Arina Puzriakova Tag Q2_21_rating was removed from gene: FLII.
Renal ciliopathies v2.3 ZNF423 Sarah Leigh reviewed gene: ZNF423: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Renal ciliopathies v2.3 XPNPEP3 Sarah Leigh commented on gene: XPNPEP3: The rating of this gene has been updated to XX following NHS Genomic Medicine Service approval.
Adult onset dystonia, chorea or related movement disorder v2.7 PDE10A Eleanor Williams Tag Q2_21_rating was removed from gene: PDE10A.
Tag Q2_21_MOI was removed from gene: PDE10A.
Adult onset dystonia, chorea or related movement disorder v2.7 PDE10A Eleanor Williams reviewed gene: PDE10A: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset dystonia, chorea or related movement disorder v2.6 PDE10A Eleanor Williams Source Expert Review Red was added to PDE10A.
Mode of inheritance for gene PDE10A was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Green List (high evidence) to Red List (low evidence)
Skeletal dysplasia v3.5 HHAT Eleanor Williams Tag Q4_21_rating was removed from gene: HHAT.
Skeletal dysplasia v3.5 HHAT Eleanor Williams changed review comment from: The rating of this gene has been updated to greenfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 AFF3 Eleanor Williams Tag Q2_22_rating was removed from gene: AFF3.
Skeletal dysplasia v3.5 AFF3 Eleanor Williams changed review comment from: The rating of this gene has been updated to greenfollowing NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 STT3A Eleanor Williams Tag Q3_22_rating was removed from gene: STT3A.
Tag Q3_22_NHS_review was removed from gene: STT3A.
Skeletal dysplasia v3.5 STT3A Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 DVL2 Eleanor Williams Tag Q2_21_NHS_review was removed from gene: DVL2.
Tag Q2_22_rating was removed from gene: DVL2.
Tag Q2_22_expert_review was removed from gene: DVL2.
Skeletal dysplasia v3.5 DVL2 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 MYH3 Eleanor Williams Tag Q3_22_rating was removed from gene: MYH3.
Skeletal dysplasia v3.5 MYH3 Eleanor Williams changed review comment from: The rating of this gene has been updated togreenand the mode of inheritance set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; to: The rating of this gene has been updated to green and the mode of inheritance set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 PRKAR1A Eleanor Williams Tag Q2_22_MOI was removed from gene: PRKAR1A.
Skeletal dysplasia v3.5 PRKAR1A Eleanor Williams changed review comment from: The mode of inheritance of this gene has been updated toMONOALLELIC, autosomal or pseudoautosomal, NOT imprintedfollowing NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 ANO5 Eleanor Williams Tag Q1_22_MOI was removed from gene: ANO5.
Skeletal dysplasia v3.5 ANO5 Eleanor Williams changed review comment from: The mode of inheritance of this gene has been updated toMONOALLELIC, autosomal or pseudoautosomal, NOT imprintedfollowing NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 COL1A2 Eleanor Williams Tag Q2_22_MOI was removed from gene: COL1A2.
Tag Q2_22_expert_review was removed from gene: COL1A2.
Skeletal dysplasia v3.5 COL1A2 Eleanor Williams changed review comment from: The mode of inheritance of this gene has been updated toMONOALLELIC, autosomal or pseudoautosomal, imprinted status unknownfollowing NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.
Nephrocalcinosis or nephrolithiasis v3.4 RRAGD Sarah Leigh Tag Q3_22_rating was removed from gene: RRAGD.
Tag Q3_22_MOI was removed from gene: RRAGD.
Tag Q3_22_NHS_review was removed from gene: RRAGD.
Skeletal dysplasia v3.5 LTBP3 Eleanor Williams Tag Q1_22_NHS_review was removed from gene: LTBP3.
Tag Q1_22_MOI was removed from gene: LTBP3.
Skeletal dysplasia v3.5 LTBP3 Eleanor Williams changed review comment from: The mode of inheritance of this gene has been updated toBOTH monoallelic and biallelic, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Nephrocalcinosis or nephrolithiasis v3.4 ATP6V0A4 Sarah Leigh Tag Q3_21_MOI was removed from gene: ATP6V0A4.
Tag watchlist_moi was removed from gene: ATP6V0A4.
Skeletal dysplasia v3.5 COPB2 Eleanor Williams Tag watchlist_moi was removed from gene: COPB2.
Skeletal dysplasia v3.5 COPB2 Eleanor Williams Tag Q1_22_MOI was removed from gene: COPB2.
Skeletal dysplasia v3.5 COPB2 Eleanor Williams changed review comment from: The mode of inheritance of this gene has been updated toBOTH monoallelic and biallelic, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Nephrocalcinosis or nephrolithiasis v3.4 SLC34A3 Sarah Leigh Tag Q3_22_MOI was removed from gene: SLC34A3.
Tag Q3_22_NHS_review was removed from gene: SLC34A3.
Skeletal dysplasia v3.5 COL9A1 Eleanor Williams Tag Q4_21_MOI was removed from gene: COL9A1.
Skeletal dysplasia v3.5 COL9A1 Eleanor Williams changed review comment from: The mode of inheritance of this gene has been updated toBOTH monoallelic and biallelic, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 DROSHA Eleanor Williams Tag Q2_22_rating was removed from gene: DROSHA.
Skeletal dysplasia v3.5 DROSHA Eleanor Williams changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remainsamber. The reviewers note that there is insufficient evidence for link to skeletal dysplasia, primarily neurological. Only 2 cases with missense variants, minor skeletal anomalies and link to gene not proven.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. The reviewers note that there is insufficient evidence for link to skeletal dysplasia, primarily neurological. Only 2 cases with missense variants, minor skeletal anomalies and link to gene not proven.
Nephrocalcinosis or nephrolithiasis v3.4 SLC34A3 Sarah Leigh commented on gene: SLC34A3
Nephrocalcinosis or nephrolithiasis v3.4 RRAGD Sarah Leigh reviewed gene: RRAGD: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Nephrocalcinosis or nephrolithiasis v3.4 ATP6V0A4 Sarah Leigh commented on gene: ATP6V0A4
Skeletal dysplasia v3.5 CSNK1G1 Eleanor Williams Tag Q1_22_rating was removed from gene: CSNK1G1.
Skeletal dysplasia v3.5 HHAT Eleanor Williams commented on gene: HHAT: The rating of this gene has been updated to greenfollowing NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 AFF3 Eleanor Williams reviewed gene: AFF3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v3.5 STT3A Eleanor Williams reviewed gene: STT3A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v3.5 DVL2 Eleanor Williams edited their review of gene: DVL2: Added comment: The rating of this gene has been updated togreenand the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Skeletal dysplasia v3.5 MYH3 Eleanor Williams commented on gene: MYH3: The rating of this gene has been updated togreenand the mode of inheritance set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 PRKAR1A Eleanor Williams commented on gene: PRKAR1A: The mode of inheritance of this gene has been updated toMONOALLELIC, autosomal or pseudoautosomal, NOT imprintedfollowing NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 ANO5 Eleanor Williams commented on gene: ANO5: The mode of inheritance of this gene has been updated toMONOALLELIC, autosomal or pseudoautosomal, NOT imprintedfollowing NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 COL1A2 Eleanor Williams commented on gene: COL1A2: The mode of inheritance of this gene has been updated toMONOALLELIC, autosomal or pseudoautosomal, imprinted status unknownfollowing NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 LTBP3 Eleanor Williams commented on gene: LTBP3: The mode of inheritance of this gene has been updated toBOTH monoallelic and biallelic, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 COPB2 Eleanor Williams commented on gene: COPB2: The mode of inheritance of this gene has been updated toBOTH monoallelic and biallelic, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 COL9A1 Eleanor Williams commented on gene: COL9A1: The mode of inheritance of this gene has been updated toBOTH monoallelic and biallelic, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.
Skeletal dysplasia v3.5 DROSHA Eleanor Williams reviewed gene: DROSHA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v3.5 CSNK1G1 Eleanor Williams reviewed gene: CSNK1G1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v3.4 STT3A Eleanor Williams Source Expert Review Green was added to STT3A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v3.4 PRKAR1A Eleanor Williams Mode of inheritance for gene PRKAR1A was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v3.4 MYH3 Eleanor Williams Source Expert Review Green was added to MYH3.
Source NHS GMS was added to MYH3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v3.4 LTBP3 Eleanor Williams Mode of inheritance for gene LTBP3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v3.4 HHAT Eleanor Williams Source Expert Review Green was added to HHAT.
Source NHS GMS was added to HHAT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v3.4 DVL2 Eleanor Williams Source Expert Review Green was added to DVL2.
Source NHS GMS was added to DVL2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v3.4 COPB2 Eleanor Williams Mode of inheritance for gene COPB2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v3.4 COL9A1 Eleanor Williams Mode of inheritance for gene COL9A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v3.4 COL1A2 Eleanor Williams Mode of inheritance for gene COL1A2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v3.4 ANO5 Eleanor Williams Mode of inheritance for gene ANO5 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v3.4 AFF3 Eleanor Williams Source Expert Review Green was added to AFF3.
Source NHS GMS was added to AFF3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v3.26 COL9A3 Achchuthan Shanmugasundram commented on gene: COL9A3: The to_be_confirmed_NHSE tag has been added, as further NHSE review is required before changing the rating and mode of inheritance of this gene.
Retinal disorders v3.26 COL9A2 Achchuthan Shanmugasundram commented on gene: COL9A2: The to_be_confirmed_NHSE tag has been added, as further NHSE review is required before promoting this gene to green.
Retinal disorders v3.26 COL9A1 Achchuthan Shanmugasundram commented on gene: COL9A1: The to_be_confirmed_NHSE tag has been added, as further NHSE review is required before promoting this gene to green.
Retinal disorders v3.26 COL2A1 Achchuthan Shanmugasundram commented on gene: COL2A1: The to_be_confirmed_NHSE tag has been added, as further NHSE review is required before promoting this gene to green.
Retinal disorders v3.26 COL11A1 Achchuthan Shanmugasundram commented on gene: COL11A1: The to_be_confirmed_NHSE tag has been added, as further NHSE review is required before promoting this gene to green.
Retinal disorders v3.26 IRX6 Achchuthan Shanmugasundram reviewed gene: IRX6: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v3.26 IRX5 Achchuthan Shanmugasundram reviewed gene: IRX5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v3.26 PRPF6 Achchuthan Shanmugasundram reviewed gene: PRPF6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v3.26 POMGNT2 Achchuthan Shanmugasundram commented on gene: POMGNT2: The rating of this gene has been updated to Amber and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Retinal disorders v3.26 STN1 Achchuthan Shanmugasundram commented on gene: STN1: 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.
Retinal disorders v3.26 SSBP1 Achchuthan Shanmugasundram commented on gene: SSBP1
Retinal disorders v3.26 RNU4ATAC Achchuthan Shanmugasundram reviewed gene: RNU4ATAC: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v3.26 PEX6 Achchuthan Shanmugasundram commented on gene: PEX6
Retinal disorders v3.26 ARSG Achchuthan Shanmugasundram reviewed gene: ARSG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v3.26 AFG3L2 Achchuthan Shanmugasundram commented on gene: AFG3L2
Retinal disorders v3.26 ACO2 Achchuthan Shanmugasundram commented on gene: ACO2
Retinal disorders v3.26 RGR Achchuthan Shanmugasundram reviewed gene: RGR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v3.26 POMT1 Achchuthan Shanmugasundram reviewed gene: POMT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v3.26 COL2A1 Achchuthan Shanmugasundram edited their review of gene: COL2A1: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Retinal disorders v3.25 STN1 Achchuthan Shanmugasundram Source NHS GMS was added to STN1.
Source Expert Review Green was added to STN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v3.25 SSBP1 Achchuthan Shanmugasundram Source NHS GMS was added to SSBP1.
Mode of inheritance for gene SSBP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Retinal disorders v3.25 RNU4ATAC Achchuthan Shanmugasundram Source NHS GMS was added to RNU4ATAC.
Source Expert Review Green was added to RNU4ATAC.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v3.25 RGR Achchuthan Shanmugasundram Source Expert Review Green was added to RGR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v3.25 POMT1 Achchuthan Shanmugasundram Source NHS GMS was added to POMT1.
Source Expert Review Green was added to POMT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v3.25 POMGNT2 Achchuthan Shanmugasundram Source NHS GMS was added to POMGNT2.
Retinal disorders v3.25 PEX6 Achchuthan Shanmugasundram Source NHS GMS was added to PEX6.
Mode of inheritance for gene PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Retinal disorders v3.25 COL2A1 Achchuthan Shanmugasundram Source Expert Review Green was added to COL2A1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Retinal disorders v3.25 ARSG Achchuthan Shanmugasundram Source Expert Review Green was added to ARSG.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v3.25 AFG3L2 Achchuthan Shanmugasundram Mode of inheritance for gene AFG3L2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Retinal disorders v3.25 ACO2 Achchuthan Shanmugasundram Mode of inheritance for gene ACO2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic neuropathy v3.7 TFG Achchuthan Shanmugasundram Tag Q3_21_rating was removed from gene: TFG.
Dilated and arrhythmogenic cardiomyopathy v2.4 RRAGD Arina Puzriakova Tag Q3_22_rating was removed from gene: RRAGD.
Dilated and arrhythmogenic cardiomyopathy v2.4 TBX5 Arina Puzriakova reviewed gene: TBX5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Dilated and arrhythmogenic cardiomyopathy v2.4 SPEG Arina Puzriakova reviewed gene: SPEG: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Dilated and arrhythmogenic cardiomyopathy v2.4 RRAGD Arina Puzriakova reviewed gene: RRAGD: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Dilated and arrhythmogenic cardiomyopathy v2.4 RPL3L Arina Puzriakova reviewed gene: RPL3L: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Dilated and arrhythmogenic cardiomyopathy v2.4 NRAP Arina Puzriakova reviewed gene: NRAP: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Dilated and arrhythmogenic cardiomyopathy v2.4 MYLK3 Arina Puzriakova reviewed gene: MYLK3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Dilated and arrhythmogenic cardiomyopathy v2.4 FLII Arina Puzriakova reviewed gene: FLII: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Dilated and arrhythmogenic cardiomyopathy v2.3 RRAGD Arina Puzriakova Source NHS GMS was added to RRAGD.
Skeletal ciliopathies v2.5 CSPP1 Eleanor Williams Tag Q4_21_rating was removed from gene: CSPP1.
Skeletal ciliopathies v2.5 CSPP1 Eleanor Williams commented on gene: CSPP1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Skeletal ciliopathies v2.4 CSPP1 Eleanor Williams Source Expert Review Green was added to CSPP1.
Source NHS GMS was added to CSPP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v3.7 SSBP1 Achchuthan Shanmugasundram Tag Q1_22_MOI was removed from gene: SSBP1.
Optic neuropathy v3.7 SPG7 Achchuthan Shanmugasundram Tag Q3_22_MOI was removed from gene: SPG7.
Tag Q3_22_NHS_review was removed from gene: SPG7.
Optic neuropathy v3.7 SLC44A1 Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: SLC44A1.
Optic neuropathy v3.7 OPA1 Achchuthan Shanmugasundram Tag Q2_22_MOI was removed from gene: OPA1.
Optic neuropathy v3.7 NDUFA12 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: NDUFA12.
Nephrocalcinosis or nephrolithiasis v3.3 SLC34A3 Sarah Leigh Source NHS GMS was added to SLC34A3.
Mode of inheritance for gene SLC34A3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Nephrocalcinosis or nephrolithiasis v3.3 RRAGD Sarah Leigh Source Expert Review Green was added to RRAGD.
Source NHS GMS was added to RRAGD.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Nephrocalcinosis or nephrolithiasis v3.3 ATP6V0A4 Sarah Leigh Source NHS GMS was added to ATP6V0A4.
Mode of inheritance for gene ATP6V0A4 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v3.7 ISCA2 Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: ISCA2.
Limb disorders v3.6 UBA2 Eleanor Williams Tag Q4_21_rating was removed from gene: UBA2.
Limb disorders v3.6 SCUBE3 Eleanor Williams Tag Q4_21_rating was removed from gene: SCUBE3.
Optic neuropathy v3.7 EPRS Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: EPRS.
Limb disorders v3.6 RAD51 Eleanor Williams Tag Q4_21_rating was removed from gene: RAD51.
Limb disorders v3.6 LTBP1 Eleanor Williams Tag Q3_21_rating was removed from gene: LTBP1.
Limb disorders v3.6 KCNN3 Eleanor Williams Tag Q2_21_rating was removed from gene: KCNN3.
Limb disorders v3.6 DLX5 Eleanor Williams Tag Q3_21_MOI was removed from gene: DLX5.
Limb disorders v3.6 DLX5 Eleanor Williams changed review comment from: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Limb disorders v3.6 DLX5 Eleanor Williams changed review comment from: The mode of inheritance of this gene has been updated toBOTH monoallelic and biallelic, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomalfollowing NHS Genomic Medicine Service approval.
Limb disorders v3.6 HEATR3 Eleanor Williams Tag Q3_22_rating was removed from gene: HEATR3.
Tag Q3_22_MOI was removed from gene: HEATR3.
Limb disorders v3.6 UBA2 Eleanor Williams commented on gene: UBA2: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Limb disorders v3.6 SCUBE3 Eleanor Williams edited their review of gene: SCUBE3: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Limb disorders v3.6 RAD51 Eleanor Williams reviewed gene: RAD51: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Limb disorders v3.6 LTBP1 Eleanor Williams commented on gene: LTBP1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Limb disorders v3.6 KCNN3 Eleanor Williams reviewed gene: KCNN3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Limb disorders v3.6 DLX5 Eleanor Williams commented on gene: DLX5
Limb disorders v3.6 HEATR3 Eleanor Williams reviewed gene: HEATR3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Limb disorders v3.5 UBA2 Eleanor Williams Source Expert Review Green was added to UBA2.
Source NHS GMS was added to UBA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Limb disorders v3.5 SCUBE3 Eleanor Williams Source Expert Review Green was added to SCUBE3.
Source NHS GMS was added to SCUBE3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Limb disorders v3.5 RAD51 Eleanor Williams Source Expert Review Green was added to RAD51.
Source NHS GMS was added to RAD51.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Limb disorders v3.5 LTBP1 Eleanor Williams Source Expert Review Green was added to LTBP1.
Source NHS GMS was added to LTBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Limb disorders v3.5 KCNN3 Eleanor Williams Source Expert Review Green was added to KCNN3.
Source NHS GMS was added to KCNN3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Limb disorders v3.5 HEATR3 Eleanor Williams Source Expert Review Green was added to HEATR3.
Source NHS GMS was added to HEATR3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Limb disorders v3.5 DLX5 Eleanor Williams Source NHS GMS was added to DLX5.
Mode of inheritance for gene DLX5 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic neuropathy v3.7 C19orf12 Achchuthan Shanmugasundram Tag Q2_22_MOI was removed from gene: C19orf12.
Optic neuropathy v3.7 ATG7 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: ATG7.
Optic neuropathy v3.7 ACO2 Achchuthan Shanmugasundram Tag Q2_22_MOI was removed from gene: ACO2.
Tag Q2_22_NHS_review was removed from gene: ACO2.
Optic neuropathy v3.7 DNAJC30 Achchuthan Shanmugasundram reviewed gene: DNAJC30: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Optic neuropathy v3.7 TFG Achchuthan Shanmugasundram reviewed gene: TFG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Optic neuropathy v3.7 SSBP1 Achchuthan Shanmugasundram commented on gene: SSBP1
Optic neuropathy v3.7 SPG7 Achchuthan Shanmugasundram commented on gene: SPG7
Optic neuropathy v3.7 SLC44A1 Achchuthan Shanmugasundram reviewed gene: SLC44A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Optic neuropathy v3.7 OPA1 Achchuthan Shanmugasundram commented on gene: OPA1
Optic neuropathy v3.7 NDUFA12 Achchuthan Shanmugasundram reviewed gene: NDUFA12: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Optic neuropathy v3.7 ISCA2 Achchuthan Shanmugasundram reviewed gene: ISCA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Optic neuropathy v3.7 EPRS Achchuthan Shanmugasundram reviewed gene: EPRS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Optic neuropathy v3.7 C19orf12 Achchuthan Shanmugasundram commented on gene: C19orf12
Optic neuropathy v3.7 ATG7 Achchuthan Shanmugasundram reviewed gene: ATG7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Optic neuropathy v3.7 ACO2 Achchuthan Shanmugasundram commented on gene: ACO2
Optic neuropathy v3.6 TFG Achchuthan Shanmugasundram Source Expert Review Green was added to TFG.
Source NHS GMS was added to TFG.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v3.6 SSBP1 Achchuthan Shanmugasundram Source NHS GMS was added to SSBP1.
Mode of inheritance for gene SSBP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Green List (high evidence) to Red List (low evidence)
Optic neuropathy v3.6 SPG7 Achchuthan Shanmugasundram Source NHS GMS was added to SPG7.
Mode of inheritance for gene SPG7 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Optic neuropathy v3.6 SLC44A1 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC44A1.
Source NHS GMS was added to SLC44A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v3.6 OPA1 Achchuthan Shanmugasundram Source NHS GMS was added to OPA1.
Mode of inheritance for gene OPA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic neuropathy v3.6 NDUFA12 Achchuthan Shanmugasundram Source Expert Review Green was added to NDUFA12.
Source NHS GMS was added to NDUFA12.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v3.6 ISCA2 Achchuthan Shanmugasundram Source Expert Review Green was added to ISCA2.
Source NHS GMS was added to ISCA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v3.6 EPRS Achchuthan Shanmugasundram Source Expert Review Green was added to EPRS.
Source NHS GMS was added to EPRS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v3.6 DNAJC30 Achchuthan Shanmugasundram gene: DNAJC30 was added
gene: DNAJC30 was added to Optic neuropathy. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: DNAJC30 was set to BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v3.6 C19orf12 Achchuthan Shanmugasundram Source NHS GMS was added to C19orf12.
Mode of inheritance for gene C19orf12 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic neuropathy v3.6 ATG7 Achchuthan Shanmugasundram Source Expert Review Green was added to ATG7.
Source NHS GMS was added to ATG7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v3.6 ACO2 Achchuthan Shanmugasundram Source NHS GMS was added to ACO2.
Mode of inheritance for gene ACO2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ophthalmological ciliopathies v2.6 TBC1D32 Achchuthan Shanmugasundram Tag Q3_21_rating was removed from gene: TBC1D32.
Ophthalmological ciliopathies v2.6 LAMA1 Achchuthan Shanmugasundram Tag Q3_21_rating was removed from gene: LAMA1.
Tag Q3_21_expert_review was removed from gene: LAMA1.
Ophthalmological ciliopathies v2.6 ARL3 Achchuthan Shanmugasundram Tag Q4_21_rating was removed from gene: ARL3.
Ophthalmological ciliopathies v2.6 TBC1D32 Achchuthan Shanmugasundram reviewed gene: TBC1D32: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ophthalmological ciliopathies v2.6 ARL3 Achchuthan Shanmugasundram reviewed gene: ARL3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ophthalmological ciliopathies v2.6 LAMA1 Achchuthan Shanmugasundram reviewed gene: LAMA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ophthalmological ciliopathies v2.5 TBC1D32 Achchuthan Shanmugasundram Source Expert Review Green was added to TBC1D32.
Source NHS GMS was added to TBC1D32.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ophthalmological ciliopathies v2.5 LAMA1 Achchuthan Shanmugasundram Source Expert Review Green was added to LAMA1.
Source NHS GMS was added to LAMA1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ophthalmological ciliopathies v2.5 ARL3 Achchuthan Shanmugasundram Source Expert Review Green was added to ARL3.
Source NHS GMS was added to ARL3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Catecholaminergic polymorphic VT v3.3 TECRL Arina Puzriakova Tag Q3_21_rating was removed from gene: TECRL.
Catecholaminergic polymorphic VT v3.3 TECRL Arina Puzriakova Source Expert Review Green was added to TECRL.
Source NHS GMS was added to TECRL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Catecholaminergic polymorphic VT v3.2 TECRL Arina Puzriakova reviewed gene: TECRL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric or syndromic cardiomyopathy v2.6 SPRED2 Arina Puzriakova Tag Q1_22_rating was removed from gene: SPRED2.
Paediatric or syndromic cardiomyopathy v2.6 LMOD2 Arina Puzriakova Tag Q2_22_rating was removed from gene: LMOD2.
Tag Q2_22_NHS_review was removed from gene: LMOD2.
Paediatric or syndromic cardiomyopathy v2.6 RRAGD Arina Puzriakova Tag Q3_22_rating was removed from gene: RRAGD.
Paediatric or syndromic cardiomyopathy v2.6 SPRED2 Arina Puzriakova reviewed gene: SPRED2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric or syndromic cardiomyopathy v2.6 LMOD2 Arina Puzriakova reviewed gene: LMOD2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric or syndromic cardiomyopathy v2.6 RRAGD Arina Puzriakova reviewed gene: RRAGD: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric or syndromic cardiomyopathy v2.5 SPRED2 Arina Puzriakova Source Expert Review Green was added to SPRED2.
Source NHS GMS was added to SPRED2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v2.5 RRAGD Arina Puzriakova Source Expert Review Green was added to RRAGD.
Source NHS GMS was added to RRAGD.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v2.5 LMOD2 Arina Puzriakova Source Expert Review Green was added to LMOD2.
Source NHS GMS was added to LMOD2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cardiac arrhythmias - additional genes v2.5 ANK2 Arina Puzriakova Tag Q3_22_rating was removed from gene: ANK2.
Tag Q3_22_expert_review was removed from gene: ANK2.
Cardiac arrhythmias - additional genes v2.5 GNB5 Arina Puzriakova Tag Q4_21_rating was removed from gene: GNB5.
Cardiac arrhythmias - additional genes v2.5 GNB5 Arina Puzriakova Source Expert Review Green was added to GNB5.
Source NHS GMS was added to GNB5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cardiac arrhythmias - additional genes v2.5 ANK2 Arina Puzriakova Source Expert Review Red was added to ANK2.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Cardiac arrhythmias - additional genes v2.4 GNB5 Arina Puzriakova commented on gene: GNB5: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Cardiac arrhythmias - additional genes v2.4 ANK2 Arina Puzriakova reviewed gene: ANK2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood solid tumours v3.4 MAX Arina Puzriakova Tag Q3_22_rating was removed from gene: MAX.
Tag Q3_22_expert_review was removed from gene: MAX.
Childhood solid tumours v3.4 CDKN1C Arina Puzriakova Phenotypes for gene: CDKN1C were changed from Beckwith-Wiedemann Syndrome; Wilms Tumor; Beckwith-Wiedemann syndrome, 130650; IMAGE syndrome, 614732; Silver-Russell Syndrome; Beckwith-Wiedemann syndrome to Beckwith-Wiedemann syndrome, OMIM:130650
Childhood solid tumours v3.3 CDKN1C Arina Puzriakova Tag Q2_22_MOI was removed from gene: CDKN1C.
Childhood solid tumours v3.3 MAX Arina Puzriakova edited their review of gene: MAX: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Childhood solid tumours v3.3 CDKN1C Arina Puzriakova commented on gene: CDKN1C
Childhood solid tumours v3.2 MAX Arina Puzriakova Source Expert Review Green was added to MAX.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Childhood solid tumours v3.2 CDKN1C Arina Puzriakova Mode of inheritance for gene CDKN1C was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Corneal dystrophy v2.3 TGFBI Achchuthan Shanmugasundram Tag Q1_22_MOI was removed from gene: TGFBI.
Corneal dystrophy v2.3 TGFBI Achchuthan Shanmugasundram commented on gene: TGFBI
Corneal dystrophy v2.2 TGFBI Achchuthan Shanmugasundram Source NHS GMS was added to TGFBI.
Mode of inheritance for gene TGFBI was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sarcoma susceptibility v1.73 FANCC Arina Puzriakova Tag Q3_22_rating was removed from gene: FANCC.
Tag Q3_22_expert_review was removed from gene: FANCC.
Sarcoma susceptibility v1.73 FANCC Arina Puzriakova commented on gene: FANCC: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber. Expert review indicated that there is not sufficient evidence for this gene-disease association at this time.
Ovarian cancer pertinent cancer susceptibility v1.13 BRCA1 Arina Puzriakova Tag Q2_22_MOI was removed from gene: BRCA1.
Tag Q2_22_expert_review was removed from gene: BRCA1.
Ovarian cancer pertinent cancer susceptibility v1.13 BRCA1 Arina Puzriakova commented on gene: BRCA1: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Ovarian cancer pertinent cancer susceptibility v1.12 BRCA1 Arina Puzriakova Source NHS GMS was added to BRCA1.
Mode of inheritance for gene BRCA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Haematological malignancies cancer susceptibility v3.3 RAD21 Arina Puzriakova Tag Q4_22_promote_green was removed from gene: RAD21.
Tag Q4_22_expert_review was removed from gene: RAD21.
Haematological malignancies cancer susceptibility v3.3 MBD4 Arina Puzriakova Tag Q3_22_rating was removed from gene: MBD4.
Tag Q3_22_expert_review was removed from gene: MBD4.
Haematological malignancies cancer susceptibility v3.3 RPS15 Arina Puzriakova Tag Q3_22_rating was removed from gene: RPS15.
Tag Q3_22_expert_review was removed from gene: RPS15.
Haematological malignancies cancer susceptibility v3.3 RPL27 Arina Puzriakova Tag Q3_22_rating was removed from gene: RPL27.
Tag Q3_22_expert_review was removed from gene: RPL27.
Haematological malignancies cancer susceptibility v3.3 ERCC6L2 Arina Puzriakova Tag Q2_22_rating was removed from gene: ERCC6L2.
Tag Q2_22_NHS_review was removed from gene: ERCC6L2.
Haematological malignancies cancer susceptibility v3.3 RAD21 Arina Puzriakova edited their review of gene: RAD21: Added comment: The rating of this gene has been updated to Green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Haematological malignancies cancer susceptibility v3.3 MBD4 Arina Puzriakova edited their review of gene: MBD4: Added comment: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Haematological malignancies cancer susceptibility v3.3 RPS15 Arina Puzriakova edited their review of gene: RPS15: Added comment: The rating of this gene has been updated to Red following NHS Genomic Medicine Service approval.; Changed rating: RED
Haematological malignancies cancer susceptibility v3.3 RPL27 Arina Puzriakova reviewed gene: RPL27: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Haematological malignancies cancer susceptibility v3.3 ERCC6L2 Arina Puzriakova reviewed gene: ERCC6L2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Haematological malignancies cancer susceptibility v3.2 RPS15 Arina Puzriakova Source NHS GMS was added to RPS15.
Source Expert Review Red was added to RPS15.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Haematological malignancies cancer susceptibility v3.2 RPL27 Arina Puzriakova Source NHS GMS was added to RPL27.
Source Expert Review Red was added to RPL27.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Haematological malignancies cancer susceptibility v3.2 RAD21 Arina Puzriakova Source Expert Review Green was added to RAD21.
Source NHS GMS was added to RAD21.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Haematological malignancies cancer susceptibility v3.2 MBD4 Arina Puzriakova Source Expert Review Green was added to MBD4.
Source NHS GMS was added to MBD4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Haematological malignancies cancer susceptibility v3.2 ERCC6L2 Arina Puzriakova Source Expert Review Green was added to ERCC6L2.
Source NHS GMS was added to ERCC6L2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v3.7 FOXI1 Arina Puzriakova Tag to_be_confirmed_NHSE tag was added to gene: FOXI1.
Monogenic hearing loss v3.7 COL9A3 Arina Puzriakova Tag to_be_confirmed_NHSE tag was added to gene: COL9A3.
Bilateral congenital or childhood onset cataracts v3.3 CDK9 Achchuthan Shanmugasundram Tag Q3_22_rating was removed from gene: CDK9.
Tag Q3_22_MOI was removed from gene: CDK9.
Bilateral congenital or childhood onset cataracts v3.3 CDK9 Achchuthan Shanmugasundram reviewed gene: CDK9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Bilateral congenital or childhood onset cataracts v3.2 CDK9 Achchuthan Shanmugasundram Source Expert Review Green was added to CDK9.
Source NHS GMS was added to CDK9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Breast cancer pertinent cancer susceptibility v1.8 BRCA1 Arina Puzriakova Tag Q2_22_MOI was removed from gene: BRCA1.
Tag Q2_22_expert_review was removed from gene: BRCA1.
Monogenic hearing loss v3.7 USP48 Arina Puzriakova Tag Q4_21_rating was removed from gene: USP48.
Monogenic hearing loss v3.7 SPATA5L1 Arina Puzriakova Tag Q1_22_rating was removed from gene: SPATA5L1.
Monogenic hearing loss v3.7 RNF220 Arina Puzriakova Tag Q4_21_rating was removed from gene: RNF220.
Monogenic hearing loss v3.7 PBX1 Arina Puzriakova Tag Q4_21_rating was removed from gene: PBX1.
Monogenic hearing loss v3.7 OGDHL Arina Puzriakova Tag Q3_22_rating was removed from gene: OGDHL.
Monogenic hearing loss v3.7 LMX1A Arina Puzriakova Tag Q1_22_MOI was removed from gene: LMX1A.
Monogenic hearing loss v3.7 KCNJ16 Arina Puzriakova Tag Q2_22_rating was removed from gene: KCNJ16.
Monogenic hearing loss v3.7 GREB1L Arina Puzriakova Tag Q2_21_rating was removed from gene: GREB1L.
Monogenic hearing loss v3.7 GGPS1 Arina Puzriakova Tag Q4_21_rating was removed from gene: GGPS1.
Breast cancer pertinent cancer susceptibility v1.8 BRCA1 Arina Puzriakova commented on gene: BRCA1: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Breast cancer pertinent cancer susceptibility v1.7 BRCA1 Arina Puzriakova Source NHS GMS was added to BRCA1.
Mode of inheritance for gene BRCA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v3.7 CRYM Arina Puzriakova Tag Q2_21_rating was removed from gene: CRYM.
Monogenic hearing loss v3.7 CLDN9 Arina Puzriakova Tag Q4_21_rating was removed from gene: CLDN9.
Monogenic hearing loss v3.7 CEACAM16 Arina Puzriakova Tag Q4_21_MOI was removed from gene: CEACAM16.
Monogenic hearing loss v3.7 AP1S1 Arina Puzriakova Tag Q2_21_rating was removed from gene: AP1S1.
Monogenic hearing loss v3.7 ADGRV1 Arina Puzriakova Tag Q1_22_MOI was removed from gene: ADGRV1.
Monogenic hearing loss v3.7 FOXI1 Arina Puzriakova commented on gene: FOXI1
Monogenic hearing loss v3.7 COL9A3 Arina Puzriakova commented on gene: COL9A3
Monogenic hearing loss v3.7 USP48 Arina Puzriakova reviewed gene: USP48: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v3.7 SPATA5L1 Arina Puzriakova reviewed gene: SPATA5L1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v3.7 RNF220 Arina Puzriakova reviewed gene: RNF220: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v3.7 PBX1 Arina Puzriakova reviewed gene: PBX1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v3.7 OGDHL Arina Puzriakova edited their review of gene: OGDHL: 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
Monogenic hearing loss v3.7 LMX1A Arina Puzriakova commented on gene: LMX1A
Monogenic hearing loss v3.7 KCNJ16 Arina Puzriakova reviewed gene: KCNJ16: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v3.7 GREB1L Arina Puzriakova reviewed gene: GREB1L: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v3.7 GGPS1 Arina Puzriakova reviewed gene: GGPS1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v3.7 CRYM Arina Puzriakova reviewed gene: CRYM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v3.7 CLDN9 Arina Puzriakova reviewed gene: CLDN9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v3.7 CEACAM16 Arina Puzriakova commented on gene: CEACAM16
Monogenic hearing loss v3.7 AP1S1 Arina Puzriakova reviewed gene: AP1S1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v3.7 ADGRV1 Arina Puzriakova commented on gene: ADGRV1
Monogenic hearing loss v3.6 USP48 Arina Puzriakova Source NHS GMS was added to USP48.
Source Expert Review Green was added to USP48.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v3.6 SPATA5L1 Arina Puzriakova Source NHS GMS was added to SPATA5L1.
Source Expert Review Green was added to SPATA5L1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v3.6 RNF220 Arina Puzriakova Source NHS GMS was added to RNF220.
Source Expert Review Green was added to RNF220.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v3.6 PBX1 Arina Puzriakova Source NHS GMS was added to PBX1.
Source Expert Review Green was added to PBX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v3.6 OGDHL Arina Puzriakova Source NHS GMS was added to OGDHL.
Source Expert Review Green was added to OGDHL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v3.6 LMX1A Arina Puzriakova Source NHS GMS was added to LMX1A.
Mode of inheritance for gene LMX1A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v3.6 KCNJ16 Arina Puzriakova Source NHS GMS was added to KCNJ16.
Source Expert Review Green was added to KCNJ16.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v3.6 GREB1L Arina Puzriakova Source NHS GMS was added to GREB1L.
Source Expert Review Green was added to GREB1L.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v3.6 GGPS1 Arina Puzriakova Source NHS GMS was added to GGPS1.
Source Expert Review Green was added to GGPS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v3.6 CRYM Arina Puzriakova Source NHS GMS was added to CRYM.
Source Expert Review Green was added to CRYM.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Monogenic hearing loss v3.6 CLDN9 Arina Puzriakova Source NHS GMS was added to CLDN9.
Source Expert Review Green was added to CLDN9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v3.6 CEACAM16 Arina Puzriakova Source NHS GMS was added to CEACAM16.
Mode of inheritance for gene CEACAM16 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v3.6 AP1S1 Arina Puzriakova Source NHS GMS was added to AP1S1.
Source Expert Review Green was added to AP1S1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v3.6 ADGRV1 Arina Puzriakova Source NHS GMS was added to ADGRV1.
Mode of inheritance for gene ADGRV1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.215 Achchuthan Shanmugasundram Panel types changed to GMS Rare Disease
Hereditary alpha tryptasaemia v0.0 Sarah Leigh Added Panel Hereditary alpha tryptasaemia
Set panel types to: GMS Rare Disease
Hereditary isolated diabetes insipidus v0.0 Sarah Leigh Added Panel Neuropophyseal diabetes insipidus
Set panel types to: GMS Rare Disease
Inherited prostate cancer v0.0 Sarah Leigh Added Panel Inherited prostate cancer
Set panel types to: GMS Rare Disease
Intellectual disability v4.51 KDM2B Mike Spiller gene: KDM2B was added
gene: KDM2B was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: KDM2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KDM2B were set to PMID: 36322151; 35128353; 35710456
Review for gene: KDM2B was set to GREEN
Added comment: van Jaarsveld et al 2022 PMID: 36322151

Majority of variants are missense, strong evidence for hotspot in CXXC domain.(7 different de Novo missenses + 1 de Novo in frame del. Same inframe del also found de novo in NHS GMS patient. All absent from gnomAD, region highly constrained).

Also 3 LOF SNVs and 3 patients with deletions including this gene, although not all are de novo and most also have potential alternate causes.

All have developmental delay. Almost all have intellectual disability ranging from mild to moderate, speech delay common..7 with cardiac abnormalities, 4 with kidney abnormalities.

Also 2 variants published in this region in PMID: 35710456, 35904121.

KDM2B methylation episignature recorded. CXXC variants show strong clustering, highly distinct from control dataset. LOF variants (including dels) also reported to show distinct episignature from controls, and from CXXC variants. While the data supports a KDM2B LOF episignature, this is not as clear, and may not be as specific, as the CXXC signature.

Mouse model also supports importance of CXXC domain, with mice heterozygous for CXXC-deleted KDM2B showing neurological defects (PMID: 35128353).

Evidence very strong for CXXC missenses less clear for haploinsufficiency.

Overall sufficient evidence from cases and episignature evidence to include as green for ID.
Sources: Literature
Intellectual disability v4.51 ZMYM3 Sarah Leigh edited their review of gene: ZMYM3: Added comment: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. Using the MatchMaker Exchange, PMID: 36586412 reports 23 ZMYM3 variants in 27 individuals (24 males, 3 females) with a neurodevelopmental delay phenotype. Of those assessed 17/20 had intellectual disability, there were other features that overlapped between the individuals including speech delay, motor delay, ASD traits, behavioral problems, facial dys-morphism, microcephaly, short stature.; Changed rating: GREEN; Changed publications to: 36586412; Changed phenotypes to: neurodevelopmental delay
Intellectual disability v4.51 ZMYM3 Sarah Leigh Classified gene: ZMYM3 as Amber List (moderate evidence)
Intellectual disability v4.51 ZMYM3 Sarah Leigh Gene: zmym3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.50 ZMYM3 Sarah Leigh Classified gene: ZMYM3 as Red List (low evidence)
Intellectual disability v4.50 ZMYM3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v4.50 ZMYM3 Sarah Leigh Gene: zmym3 has been classified as Red List (Low Evidence).
Intellectual disability v4.49 ZMYM3 Sarah Leigh Tag Q1_23_promote_green tag was added to gene: ZMYM3.
Intellectual disability v4.49 ZMYM3 Sarah Leigh Publications for gene: ZMYM3 were set to 26350204; 24721225; 8817323
Paediatric pseudo-obstruction syndrome v0.214 Arina Puzriakova List of related panels changed from to R438
Unexplained death in infancy and sudden unexplained death in childhood v3.24 Arina Puzriakova List of related panels changed from to R441
Li Fraumeni Syndrome v0.5 Eleanor Williams Panel status changed from public to internal
Hereditary diffuse gastric cancer v0.5 Eleanor Williams Panel status changed from public to internal
Autoimmune lymphoproliferative syndrome with defective apoptosis v0.5 Eleanor Williams Panel status changed from public to internal
Ataxia telangiectasia - mutation testing v0.6 Eleanor Williams Panel status changed from public to internal
APC associated Polyposis v0.7 Eleanor Williams Panel status changed from public to internal
Alveolar capillary dysplasia with misalignment of pulmonary veins v0.5 Eleanor Williams Panel status changed from public to internal
Alstrom syndrome v0.5 Eleanor Williams Panel status changed from public to internal
Albright hereditary osteodystrophy, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, acrodysostosis and osteoma cutis v0.6 Eleanor Williams Panel status changed from public to internal
Agammaglobulinaemia with absent BTK expression v0.6 Eleanor Williams Panel status changed from public to internal
Acute intermittent porphyria v0.6 Eleanor Williams Panel status changed from public to internal
Auditory Neuropathy Spectrum Disorde v1.9 CABP2 Barbara Vona gene: CABP2 was added
gene: CABP2 was added to Auditory Neuropathy Spectrum Disorder. Sources: Literature
Mode of inheritance for gene: CABP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CABP2 were set to PMID: 28183797
Phenotypes for gene: CABP2 were set to Auditory neuropathy; auditory synaptopathy
Penetrance for gene: CABP2 were set to Complete
Mode of pathogenicity for gene: CABP2 was set to Other
Review for gene: CABP2 was set to RED
gene: CABP2 was marked as current diagnostic
Added comment: Variants in CABP2 have been reported to cause autosomal recessive non-syndromic hearing loss (DFNB93). In-depth functional studies and deep phenotyping of one of the originally published families with a homozygous loss-of-function variant (NM_016366.3:c.466G>T (p.Glu156Ter)/NM_001318496.2:c.484G>T, p.(Glu162Ter)); PMID: 22981119) presenting mid-frequency, moderate-to-severe hearing loss, uncovered transient evoked otoacoustic emissions (TEOAEs) in a 4 year-old affected individual (PMID: 28183797). The authors suggested, at least initially, that outer hair cell function is spared, thus showing the first individual with auditory synaptopathy/auditory neuropathy. A mouse model with a deletion of exons 3-4 of Cabp2 showed reduced auditory brainstem response recordings and present distortion product otoacoustic emissions. The lesion was identified to be most likely at the inner hair cell synapses, compatible with an auditory synaptopathy/auditory neuropathy. Although there are not abundant examples of CABP2 patients with auditory synapthpathy/auditory neuropathy in the literature, biallelic variants in CABP2 undoubtedly cause hearing impairment that should be further phenotyped in patients through OAE testing. Replication of this specific type of hearing deficit is needed; therefore, CABP2 merits being added to the Auditory Neuropathy gene panel.
Sources: Literature
Cytopenia - NOT Fanconi anaemia v2.1 RRAS Dmitrijs Rots gene: RRAS was added
gene: RRAS was added to Cytopenia - NOT Fanconi anaemia. Sources: Literature
Mode of inheritance for gene: RRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RRAS were set to PMID: 34935735
Phenotypes for gene: RRAS were set to Pediatric Myelodysplastic Syndrome
Penetrance for gene: RRAS were set to unknown
Mode of pathogenicity for gene: RRAS 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: RRAS was set to GREEN
Added comment: 34935735 describes a new case and provides info from 3 cases from the literature with RASopathy AND pediatric MDS. Only de novo missense variants were found. Therefore, enough evidence for green rating.
Sources: Literature
Hereditary neuropathy or pain disorder v2.16 VCP Mafalda Gomes Phenotypes for gene: VCP were changed from Amyotrophic lateral sclerosis 14, with or without frontotemporal dementia; Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia 1; Charcot-Marie-Tooth disease, type 2Y to Charcot-Marie-Tooth disease, type 2Y, OMIM:616687
Hereditary neuropathy or pain disorder v2.15 VCP Mafalda Gomes Publications for gene: VCP were set to 26574898; 25878907; 25125609
Hereditary neuropathy or pain disorder v2.14 VCP Mafalda Gomes Tag Q1_23_promote_green tag was added to gene: VCP.
Childhood onset dystonia, chorea or related movement disorder v2.7 COX20 Mafalda Gomes Phenotypes for gene: COX20 were changed from Mitochondrial complex IV deficiency, nuclear type 11, OMIM:619054 to Mitochondrial complex IV deficiency, nuclear type 11, OMIM:619054
Childhood onset dystonia, chorea or related movement disorder v2.7 COX20 Mafalda Gomes Phenotypes for gene: COX20 were changed from Mitochondrial complex IV deficiency, nuclear type 11, OMIM:619054 to Mitochondrial complex IV deficiency, nuclear type 11, OMIM:619054
Childhood onset dystonia, chorea or related movement disorder v2.7 COX20 Mafalda Gomes Phenotypes for gene: COX20 were changed from to Mitochondrial complex IV deficiency, nuclear type 11, OMIM:619054
Childhood onset dystonia, chorea or related movement disorder v2.6 COX20 Mafalda Gomes Publications for gene: COX20 were set to
Childhood onset dystonia, chorea or related movement disorder v2.5 COX20 Mafalda Gomes Tag Q1_23_promote_green tag was added to gene: COX20.
Hereditary neuropathy or pain disorder v2.14 COX20 Mafalda Gomes Phenotypes for gene: COX20 were changed from Mitochondrial complex IV deficiency, nuclear type 11, OMIM:619054 to Mitochondrial complex IV deficiency, nuclear type 11, OMIM:619054
Hereditary neuropathy or pain disorder v2.13 COX20 Mafalda Gomes Phenotypes for gene: COX20 were changed from Neuropathy to Mitochondrial complex IV deficiency, nuclear type 11, OMIM:619054
Hereditary neuropathy or pain disorder v2.12 COX20 Mafalda Gomes Publications for gene: COX20 were set to 33751098; 30656193; 24202787
Hereditary neuropathy or pain disorder v2.11 COX20 Mafalda Gomes Publications for gene: COX20 were set to 33751098
Hereditary neuropathy or pain disorder v2.10 COX20 Mafalda Gomes Tag Q1_23_promote_green tag was added to gene: COX20.
Hereditary neuropathy or pain disorder v2.10 ACOX1 Mafalda Gomes Tag Q1_23_promote_green tag was added to gene: ACOX1.
Early onset or syndromic epilepsy v3.27 CHD4 Mafalda Gomes Phenotypes for gene: CHD4 were changed from Sifrim-Hitz-Weiss syndrome, OMIM:617159 to Sifrim-Hitz-Weiss syndrome, OMIM:617159
Early onset or syndromic epilepsy v3.27 CHD4 Mafalda Gomes Phenotypes for gene: CHD4 were changed from Sifrim-Hitz-Weiss syndrome, OMIM:617159 to Sifrim-Hitz-Weiss syndrome, OMIM:617159
Early onset or syndromic epilepsy v3.27 CHD4 Mafalda Gomes Phenotypes for gene: CHD4 were changed from Sifrim-Hitz-Weiss syndrome, OMIM:617159 to Sifrim-Hitz-Weiss syndrome, OMIM:617159
Early onset or syndromic epilepsy v3.27 CHD4 Mafalda Gomes Phenotypes for gene: CHD4 were changed from Sifrim-Hitz-Weiss syndrome, OMIM:617159 to Sifrim-Hitz-Weiss syndrome, OMIM:617159
Early onset or syndromic epilepsy v3.27 CHD4 Mafalda Gomes Phenotypes for gene: CHD4 were changed from Sifrim-Hitz-Weiss syndrome, OMIM:617159 to Sifrim-Hitz-Weiss syndrome, OMIM:617159
Early onset or syndromic epilepsy v3.27 CHD4 Mafalda Gomes Phenotypes for gene: CHD4 were changed from Sifrim-Hitz-Weiss syndrome, OMIM:617159 to Sifrim-Hitz-Weiss syndrome, OMIM:617159
Early onset or syndromic epilepsy v3.26 CHD4 Mafalda Gomes Phenotypes for gene: CHD4 were changed from Sifrim-Hitz-Weiss syndrome, OMIM:617159 to Sifrim-Hitz-Weiss syndrome, OMIM:617159
Early onset or syndromic epilepsy v3.26 CHD4 Mafalda Gomes Phenotypes for gene: CHD4 were changed from Sifrim-Hitz-Weiss syndrome, MIM# 617159; Childhood idiopathic epilepsy and sinus arrhythmia to Sifrim-Hitz-Weiss syndrome, OMIM:617159
Early onset or syndromic epilepsy v3.25 CHD4 Mafalda Gomes Tag Q1_23_promote_green tag was added to gene: CHD4.
Early onset or syndromic epilepsy v3.25 ASXL3 Mafalda Gomes Phenotypes for gene: ASXL3 were changed from Bainbridge-Ropers syndrome, OMIM:615115 to Bainbridge-Ropers syndrome, OMIM:615115
Early onset or syndromic epilepsy v3.25 ASXL3 Mafalda Gomes Phenotypes for gene: ASXL3 were changed from Bainbridge-Ropers syndrome, OMIM:615115 to Bainbridge-Ropers syndrome, OMIM:615115
Early onset or syndromic epilepsy v3.25 ASXL3 Mafalda Gomes Phenotypes for gene: ASXL3 were changed from Bainbridge-Ropers syndrome, OMIM:615115 to Bainbridge-Ropers syndrome, OMIM:615115
Early onset or syndromic epilepsy v3.25 ASXL3 Mafalda Gomes Phenotypes for gene: ASXL3 were changed from Bainbridge-Ropers syndrome, OMIM:615115 to Bainbridge-Ropers syndrome, OMIM:615115
Early onset or syndromic epilepsy v3.24 ASXL3 Mafalda Gomes Phenotypes for gene: ASXL3 were changed from Bainbridge-Ropers syndrome to Bainbridge-Ropers syndrome, OMIM:615115
Early onset or syndromic epilepsy v3.23 ASXL3 Mafalda Gomes Publications for gene: ASXL3 were set to 35172777; 27901041; 34436830; 33151654
Early onset or syndromic epilepsy v3.23 ASXL3 Mafalda Gomes Publications for gene: ASXL3 were set to 35172777; 27901041; 34436830
Early onset or syndromic epilepsy v3.22 ASXL3 Mafalda Gomes Tag Q1_23_promote_green tag was added to gene: ASXL3.
Intellectual disability v4.48 BAP1 Mafalda Gomes Phenotypes for gene: BAP1 were changed from Kury-Isidor syndrome, OMIM:619762 to Kury-Isidor syndrome, OMIM:619762
Intellectual disability v4.48 BAP1 Mafalda Gomes Phenotypes for gene: BAP1 were changed from Kury-Isidor syndrome, OMIM:619762 to Kury-Isidor syndrome, OMIM:619762
Intellectual disability v4.48 BAP1 Mafalda Gomes Phenotypes for gene: BAP1 were changed from Kury-Isidor syndrome, OMIM:619762 to Kury-Isidor syndrome, OMIM:619762
Intellectual disability v4.48 BAP1 Mafalda Gomes Phenotypes for gene: BAP1 were changed from Kury-Isidor syndrome, OMIM:619762 to Kury-Isidor syndrome, OMIM:619762
Early onset or syndromic epilepsy v3.22 BAP1 Mafalda Gomes Phenotypes for gene: BAP1 were changed from Kury-Isidor syndrome, OMIM:619762 to Kury-Isidor syndrome, OMIM:619762
Intellectual disability v4.48 BAP1 Mafalda Gomes Phenotypes for gene: BAP1 were changed from Kury-Isidor syndrome, OMIM:619762 to Kury-Isidor syndrome, OMIM:619762
Early onset or syndromic epilepsy v3.22 BAP1 Mafalda Gomes Phenotypes for gene: BAP1 were changed from Kury-Isidor syndrome, OMIM:619762 to Kury-Isidor syndrome, OMIM:619762
Early onset or syndromic epilepsy v3.22 BAP1 Mafalda Gomes Phenotypes for gene: BAP1 were changed from to Kury-Isidor syndrome, OMIM:619762
Intellectual disability v4.48 BAP1 Mafalda Gomes Phenotypes for gene: BAP1 were changed from Kury-Isidor syndrome, OMIM:619762 to Kury-Isidor syndrome, OMIM:619762
Early onset or syndromic epilepsy v3.21 BAP1 Mafalda Gomes Tag Q1_23_promote_green tag was added to gene: BAP1.
Intellectual disability v4.47 BAP1 Mafalda Gomes Phenotypes for gene: BAP1 were changed from Kury-Isidor syndrome, OMIM:619762 to Kury-Isidor syndrome, OMIM:619762
Intellectual disability v4.47 BAP1 Mafalda Gomes Phenotypes for gene: BAP1 were changed from Intellectual disability; short stature; autism spectrum disorder to Kury-Isidor syndrome, OMIM:619762
Intellectual disability v4.46 BAP1 Mafalda Gomes Tag Q1_23_promote_green tag was added to gene: BAP1.
Hereditary neuropathy or pain disorder v2.10 TECPR2 Mafalda Gomes Tag Q1_23_promote_green tag was added to gene: TECPR2.
Hereditary neuropathy or pain disorder v2.10 TECPR2 Mafalda Gomes Phenotypes for gene: TECPR2 were changed from Hereditary sensory and autonomic neuropathy to Neuropathy, hereditary sensory and autonomic, type IX, with developmental delay, OMIM:615031
Childhood onset hereditary spastic paraplegia v3.7 TECPR2 Mafalda Gomes Phenotypes for gene: TECPR2 were changed from Spastic paraplegia 49, autosomal recessive, 615031 to Neuropathy, hereditary sensory and autonomic, type IX, with developmental delay, OMIM:615031
Childhood onset hereditary spastic paraplegia v3.6 TECPR2 Mafalda Gomes Publications for gene: TECPR2 were set to 23176824; 26542466
Childhood onset hereditary spastic paraplegia v3.5 TECPR2 Mafalda Gomes Tag Q1_23_promote_green tag was added to gene: TECPR2.
Hereditary neuropathy or pain disorder v2.9 TECPR2 Mafalda Gomes changed review comment from: Neuser et al. (2021) report 17 unrelated cases with a biallelic pathogenic variants in TECPR2. The study also includes 11 previously reported patients. The core manifestations in these individuals are global developmental delay/intellectual disability, muscular hypotonia, ataxia, hyporeflexia, respiratory infections, and central/nocturnal hypopnea. Peripheral neuropathy was present in two-thirds of all individuals. The majority of the pathogenic variants identified are truncating variants; however, missense variants were also found, predominantly located in the N-terminal and C-terminal regions. The TECPR2 gene is implicated in the autophagy pathway, which is critical to the development and function of the central nervous system. Loss?of?function variants in several genes of the autophagy pathway lead to both neurodevelopmental and neurodegenerative diseases. In summary, this gene should be promoted to GREEN in this panel, with autosomal recessive mode of inheritance.; to: Neuser et al. (2021) report 17 unrelated cases with a biallelic pathogenic variants in TECPR2. The study also includes 11 previously reported patients. The core manifestations in these individuals are global developmental delay/intellectual disability, muscular hypotonia, ataxia, hyporeflexia, respiratory infections, and central/nocturnal hypopnea. Peripheral neuropathy was present in two-thirds of all individuals. The majority of the pathogenic variants identified are truncating variants; however, missense variants were also found, predominantly located in the N-terminal and C-terminal regions. The TECPR2 gene is implicated in the autophagy pathway, which is critical to the development and function of the central nervous system. Loss of function variants in several genes of the autophagy pathway lead to both neurodevelopmental and neurodegenerative diseases. In summary, this gene should be promoted to GREEN in this panel, with autosomal recessive mode of inheritance.
Childhood onset hereditary spastic paraplegia v3.5 TECPR2 Mafalda Gomes changed review comment from: Neuser et al. (2021) report 17 unrelated cases with a biallelic pathogenic variants in TECPR2. The study also includes 11 previously reported patients. The core manifestations in these individuals are global developmental delay/intellectual disability, muscular hypotonia, ataxia, hyporeflexia, respiratory infections, and central/nocturnal hypopnea. Peripheral neuropathy was present in two-thirds of all individuals. The majority of the pathogenic variants identified are truncating variants; however, missense variants were also found, predominantly located in the N-terminal and C-terminal regions. The TECPR2 gene is implicated in the autophagy pathway, which is critical to the development and function of the central nervous system. Loss?of?function variants in several genes of the autophagy pathway lead to both neurodevelopmental and neurodegenerative diseases. In summary, this gene should be promoted to GREEN in this panel, with autosomal recessive mode of inheritance.; to: Neuser et al. (2021) report 17 unrelated cases with a biallelic pathogenic variants in TECPR2. The study also includes 11 previously reported patients. The core manifestations in these individuals are global developmental delay/intellectual disability, muscular hypotonia, ataxia, hyporeflexia, respiratory infections, and central/nocturnal hypopnea. Peripheral neuropathy was present in two-thirds of all individuals. The majority of the pathogenic variants identified are truncating variants; however, missense variants were also found, predominantly located in the N-terminal and C-terminal regions. The TECPR2 gene is implicated in the autophagy pathway, which is critical to the development and function of the central nervous system. Loss of function variants in several genes of the autophagy pathway lead to both neurodevelopmental and neurodegenerative diseases. In summary, this gene should be promoted to GREEN in this panel, with autosomal recessive mode of inheritance.
Childhood onset hereditary spastic paraplegia v3.5 TECPR2 Mafalda Gomes reviewed gene: TECPR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33847017; Phenotypes: Neuropathy, hereditary sensory and autonomic, type IX, with developmental delay, OMIM:615031; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v3.27 TECPR2 Mafalda Gomes Tag Q1_23_promote_green tag was added to gene: TECPR2.
Ataxia and cerebellar anomalies - narrow panel v3.27 TECPR2 Mafalda Gomes Phenotypes for gene: TECPR2 were changed from to Neuropathy, hereditary sensory and autonomic, type IX, with developmental delay, OMIM:615031
Ataxia and cerebellar anomalies - narrow panel v3.26 TECPR2 Mafalda Gomes Publications for gene: TECPR2 were set to
Ataxia and cerebellar anomalies - narrow panel v3.25 TECPR2 Mafalda Gomes changed review comment from: Neuser et al. (2021) report 17 unrelated cases with biallelic pathogenic variants in TECPR2. The study also includes 11 previously reported patients. The core manifestations in these individuals are global developmental delay/intellectual disability, muscular hypotonia, ataxia, hyporeflexia, respiratory infections, and central/nocturnal hypopnea. Peripheral neuropathy was present in two-thirds of all individuals. The majority of the pathogenic variants identified are truncating variants; however, missense variants were also found, predominantly located in the N-terminal and C-terminal regions. The TECPR2 gene is implicated in the autophagy pathway, which is critical to the development and function of the central nervous system. Loss?of?function variants in several genes of the autophagy pathway lead to both neurodevelopmental and neurodegenerative diseases. In summary, this gene should be promoted to GREEN in this panel, with autosomal recessive mode of inheritance.; to: Neuser et al. (2021) report 17 unrelated cases with biallelic pathogenic variants in TECPR2. The study also includes 11 previously reported patients. The core manifestations in these individuals are global developmental delay/intellectual disability, muscular hypotonia, ataxia, hyporeflexia, respiratory infections, and central/nocturnal hypopnea. Peripheral neuropathy was present in two-thirds of all individuals. The majority of the pathogenic variants identified are truncating variants; however, missense variants were also found, predominantly located in the N-terminal and C-terminal regions. The TECPR2 gene is implicated in the autophagy pathway, which is critical to the development and function of the central nervous system. Loss of function variants in several genes of the autophagy pathway lead to both neurodevelopmental and neurodegenerative diseases. In summary, this gene should be promoted to GREEN in this panel, with autosomal recessive mode of inheritance.
Hereditary neuropathy or pain disorder v2.9 VCP Mafalda Gomes reviewed gene: VCP: Rating: GREEN; Mode of pathogenicity: ; Publications: 25125609, 32165109, 25878907; Phenotypes: Charcot-Marie-Tooth disease, type 2Y, OMIM:616687; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ataxia and cerebellar anomalies - narrow panel v3.25 TECPR2 Mafalda Gomes reviewed gene: TECPR2: Rating: GREEN; Mode of pathogenicity: ; Publications: 33847017; Phenotypes: Neuropathy, hereditary sensory and autonomic, type IX, with developmental delay, OMIM:615031; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v2.9 TECPR2 Mafalda Gomes reviewed gene: TECPR2: Rating: GREEN; Mode of pathogenicity: ; Publications: 33847017; Phenotypes: Neuropathy, hereditary sensory and autonomic, type IX, with developmental delay, OMIM:615031; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v2.5 COX20 Mafalda Gomes reviewed gene: COX20: Rating: GREEN; Mode of pathogenicity: ; Publications: 30656193, 33751098, 24202787; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 11, OMIM:619054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v2.9 COX20 Mafalda Gomes reviewed gene: COX20: Rating: GREEN; Mode of pathogenicity: ; Publications: 30656193, 33751098, 24202787; Phenotypes: Mitochondrial complex IV deficiency, nuclear type 11, OMIM:619054; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v3.5 ACOX1 Mafalda Gomes reviewed gene: ACOX1: Rating: GREEN; Mode of pathogenicity: ; Publications: 32169171; Phenotypes: Mitchell syndrome, OMIM:618960; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary neuropathy or pain disorder v2.9 ACOX1 Mafalda Gomes reviewed gene: ACOX1: Rating: GREEN; Mode of pathogenicity: ; Publications: 32169171; Phenotypes: Mitchell syndrome, OMIM:618960; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v3.21 CHD4 Mafalda Gomes reviewed gene: CHD4: Rating: GREEN; Mode of pathogenicity: ; Publications: 34109749; Phenotypes: Sifrim-Hitz-Weiss syndrome, OMIM:617159; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Early onset or syndromic epilepsy v3.21 ASXL3 Mafalda Gomes reviewed gene: ASXL3: Rating: GREEN; Mode of pathogenicity: ; Publications: 34436830, 33151654; Phenotypes: Bainbridge-Ropers syndrome, OMIM:615115; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v4.46 BAP1 Mafalda Gomes commented on gene: BAP1: Kry et al. (2022) performed trio-WES in a cohort with a rare syndromic NDD and identified de novo missense variants in 11 unrelated individuals. All individuals had DD or ID characterised notably by speech (11/11) and motor delay (6/11). Additional common characteristics were hypotonia, (7/11), seizures (6/11), and abnormal behaviour (8/10), including ASD, ADHD, and hypersensitivity. Almost all individuals showed dysmorphic facial features (10/11), and more than half (6/11) had skeletal malformations involving the hands, feet, or spine. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. In T cells isolated from two affected children, H2A deubiquitination was impaired. In summary, this gene should be promoted to GREEN in this panel, with autosomal dominant mode of inheritance.
Early onset or syndromic epilepsy v3.21 BAP1 Mafalda Gomes commented on gene: BAP1: Kry et al. (2022) performed trio-WES in a cohort with a rare syndromic NDD and identified de novo missense variants in 11 unrelated individuals. All individuals had DD or ID characterised notably by speech (11/11) and motor delay (6/11). Additional common characteristics were hypotonia, (7/11), seizures (6/11), and abnormal behaviour (8/10), including ASD, ADHD, and hypersensitivity. Almost all individuals showed dysmorphic facial features (10/11), and more than half (6/11) had skeletal malformations involving the hands, feet, or spine. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. In T cells isolated from two affected children, H2A deubiquitination was impaired. In summary, this gene should be promoted to GREEN in this panel, with autosomal dominant mode of inheritance.
Hereditary neuropathy or pain disorder v2.8 VCP Mafalda Gomes Mode of inheritance for gene VCP was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ataxia and cerebellar anomalies - narrow panel v3.24 TECPR2 Mafalda Gomes gene: TECPR2 was added
gene: TECPR2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert Review Amber
Mode of inheritance for gene: TECPR2 was set to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v2.8 TECPR2 Mafalda Gomes Source Expert Review Amber was added to TECPR2.
Rating Changed from No List (delete) to Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v2.4 COX20 Mafalda Gomes Source Expert Review Amber was added to COX20.
Mode of inheritance for gene COX20 was changed from to BIALLELIC, autosomal or pseudoautosomal
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v2.8 COX20 Mafalda Gomes Source Expert Review Amber was added to COX20.
Rating Changed from No List (delete) to Amber List (moderate evidence)
Monogenic hearing loss v3.4 ACOX1 Mafalda Gomes gene: ACOX1 was added
gene: ACOX1 was added to Monogenic hearing loss. Sources: Expert Review Amber
Mode of inheritance for gene: ACOX1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary neuropathy or pain disorder v2.8 ACOX1 Mafalda Gomes Source Expert Review Amber was added to ACOX1.
Mode of inheritance for gene ACOX1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rating Changed from No List (delete) to Amber List (moderate evidence)
Early onset or syndromic epilepsy v3.20 CHD4 Mafalda Gomes Source Expert Review Amber was added to CHD4.
Mode of inheritance for gene CHD4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rating Changed from No List (delete) to Amber List (moderate evidence)
Early onset or syndromic epilepsy v3.20 ASXL3 Mafalda Gomes Source Expert Review Amber was added to ASXL3.
Mode of inheritance for gene ASXL3 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rating Changed from No List (delete) to Amber List (moderate evidence)
Intellectual disability v4.45 BAP1 Mafalda Gomes Source Expert Review Amber was added to BAP1.
Mode of inheritance for gene BAP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rating Changed from No List (delete) to Amber List (moderate evidence)
Early onset or syndromic epilepsy v3.20 BAP1 Mafalda Gomes Source Expert Review Amber was added to BAP1.
Rating Changed from No List (delete) to Amber List (moderate evidence)
Intellectual disability v4.44 TMEM147 Sarah Leigh Classified gene: TMEM147 as Amber List (moderate evidence)
Intellectual disability v4.44 TMEM147 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v4.44 TMEM147 Sarah Leigh Gene: tmem147 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.43 TMEM147 Sarah Leigh gene: TMEM147 was added
gene: TMEM147 was added to Intellectual disability. Sources: Literature
Q1_23_promote_green tags were added to gene: TMEM147.
Mode of inheritance for gene: TMEM147 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMEM147 were set to 36044892
Phenotypes for gene: TMEM147 were set to Neurodevelopmental disorder with facial dysmorphism, absent language, and pseudo-Pelger-Huet anomaly, OMIM:620075
Review for gene: TMEM147 was set to GREEN
Added comment: Associated with relevant phenotype in OMIM and as strong Gen2Phen gene. PMID: 36044892 reports 12 variants in at least 15 unrelated derived from GeneMatcher. Supportive functional evidence is also presented.
Sources: Literature
Fetal anomalies v2.8 KIF21A Hannah Robinson gene: KIF21A was added
gene: KIF21A was added to Fetal anomalies. Sources: Literature,NHS GMS
Mode of inheritance for gene: KIF21A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF21A were set to 34740919
Phenotypes for gene: KIF21A were set to Arthrogryposis; fetal akinesia
Penetrance for gene: KIF21A were set to unknown
Review for gene: KIF21A was set to GREEN
gene: KIF21A was marked as current diagnostic
Added comment: Falb et al 2023 (PMID: 34740919) describe two unrelated families in which biallelic loss of function variants segregated with a severe form of fetal akinesia characterised by arthrogryposis multiplex, pulmonary hypoplasia and variable facial dysmorphisms.

Exeter Genomics Laboratory has identified an unrelated third case homozygous for a nonsense variant in KIF21A. The patient had an antenatal diagnosis of talipes, arthrogryposis, polyhydramnios and lack of fetal movements. At birth, all joints displayed fixed flexion deformities, no primitive reflexes, poor muscle bulk and care was re-oriented shortly after birth.

Taken together, three unrelated cases including segregation evidence in the published families provides sufficient evidence for the gene-disease association.
Sources: Literature, NHS GMS
Arthrogryposis v4.3 KIF21A Hannah Robinson gene: KIF21A was added
gene: KIF21A was added to Arthrogryposis. Sources: Literature,NHS GMS
Mode of inheritance for gene: KIF21A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF21A were set to 34740919
Phenotypes for gene: KIF21A were set to Arthrogryposis; fetal akinesia
Penetrance for gene: KIF21A were set to unknown
Review for gene: KIF21A was set to GREEN
gene: KIF21A was marked as current diagnostic
Added comment: Falb et al 2023 (PMID: 34740919) describe two unrelated families in which biallelic loss of function variants segregated with a severe form of fetal akinesia characterised by arthrogryposis multiplex, pulmonary hypoplasia and variable facial dysmorphisms.

Exeter Genomics Laboratory has identified an unrelated third case homozygous for a nonsense variant in KIF21A. The patient had an antenatal diagnosis of talipes, arthrogryposis, polyhydramnios and lack of fetal movements. At birth, all joints displayed fixed flexion deformities, no primitive reflexes, poor muscle bulk and care was re-oriented shortly after birth.

Taken together, three unrelated cases including segregation evidence in the published families provides sufficient evidence for the gene-disease association.
Sources: Literature, NHS GMS
Ataxia and cerebellar anomalies - narrow panel v3.23 UCHL1 Sarah Leigh Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive, OMIM:615491 to Spastic paraplegia 79, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209
Hereditary ataxia with onset in adulthood v3.8 UCHL1 Sarah Leigh Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive, OMIM:615491 to Spastic paraplegia 79, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209
Adult onset hereditary spastic paraplegia v2.5 UCHL1 Sarah Leigh Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive, OMIM:615491 to Spastic paraplegia 79, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209
Ataxia and cerebellar anomalies - narrow panel v3.22 UCHL1 Sarah Leigh reviewed gene: UCHL1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Adult onset dystonia, chorea or related movement disorder v2.5 UCHL1 Sarah Leigh reviewed gene: UCHL1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v3.7 UCHL1 Sarah Leigh edited their review of gene: UCHL1: Added comment: In addition to previous reports of Spastic paraplegia 79, autosomal recessive (OMIM:615491), PMID: 35986737 reports a neurodegenerative disorder with spasticity, ataxia, neuropathy, and optic atrophy in cases with heterozygous UCHL1 variants. The variants included 13 heterozygous loss-of-function variants (15 families) and a heterozygous in-frame insertion (3 families). The affected individuals mainly presented with spasticity (24/31), ataxia (28/31), neuropathy (11/21), and optic atrophy (9/17), it was also noted in PMID: 35986737 that the condition onset in dominant cases was median 49 years (12-70 years) and in recessive was 7.5 years (2-10 years).; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Adult onset hereditary spastic paraplegia v2.4 UCHL1 Sarah Leigh edited their review of gene: UCHL1: Added comment: In addition to previous reports of Spastic paraplegia 79, autosomal recessive (OMIM:615491), PMID: 35986737 reports a neurodegenerative disorder with spasticity, ataxia, neuropathy, and optic atrophy in cases with heterozygous UCHL1 variants. The variants included 13 heterozygous loss-of-function variants (15 families) and a heterozygous in-frame insertion (3 families). The affected individuals mainly presented with spasticity (24/31), ataxia (28/31), neuropathy (11/21), and optic atrophy (9/17), it was also noted in PMID: 35986737 that the condition onset in dominant cases was median 49 years (12-70 years) and in recessive was 7.5 years (2-10 years).; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary ataxia v1.314 UCHL1 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. Numerous UCHL1 variants have been reported, including 13 heterozygous loss-of-function variants (15 families) and a heterozygous inframe insertion (3 families) in PMID: 35986737. These affected individuals mainly presented with spasticity (24/31), ataxia (28/31), neuropathy (11/21), and optic atrophy (9/17), it was also noted in PMID: 35986737 that the condition onset in dominant cases was median 49 years (12-70 years) and in recessive was 7.5 years (2-10 years).; to: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. Numerous UCHL1 variants have been reported, including 13 heterozygous loss-of-function variants (15 families) and a heterozygous inframe insertion (3 families) in PMID: 35986737. The affected individuals mainly presented with spasticity (24/31), ataxia (28/31), neuropathy (11/21), and optic atrophy (9/17), it was also noted in PMID: 35986737 that the condition onset in dominant cases was median 49 years (12-70 years) and in recessive was 7.5 years (2-10 years).
Hereditary ataxia v1.314 UCHL1 Sarah Leigh edited their review of gene: UCHL1: Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. Numerous UCHL1 variants have been reported, including 13 heterozygous loss-of-function variants (15 families) and a heterozygous inframe insertion (3 families) in PMID: 35986737. These affected individuals mainly presented with spasticity (24/31), ataxia (28/31), neuropathy (11/21), and optic atrophy (9/17), it was also noted in PMID: 35986737 that the condition onset in dominant cases was median 49 years (12-70 years) and in recessive was 7.5 years (2-10 years).; Changed rating: GREEN; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary ataxia v1.314 UCHL1 Sarah Leigh Added comment: Comment on mode of inheritance: In addition to previous reports of Spastic paraplegia 79, autosomal recessive (OMIM:615491), PMID: 35986737 reports a neurodegenerative disorder with spasticity, ataxia, neuropathy, and optic atrophy in cases with heterozygous loss of function UCHL1 variants.
Hereditary ataxia v1.314 UCHL1 Sarah Leigh Mode of inheritance for gene: UCHL1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v3.22 UCHL1 Sarah Leigh Publications for gene: UCHL1 were set to 23359680; 28007905; 29735986; 32656641; 11555633; 33159930
Adult onset dystonia, chorea or related movement disorder v2.5 UCHL1 Sarah Leigh Phenotypes for gene: UCHL1 were changed from {?Parkinson disease 5, susceptibility to}, OMIM:613643 to Spastic paraplegia 79, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209; ?{Parkinson disease 5, susceptibility to}, OMIM:613643; Parkinson disease 5, autosomal dominant, susceptibility to' MONDO:0013340
Adult onset dystonia, chorea or related movement disorder v2.4 UCHL1 Sarah Leigh Publications for gene: UCHL1 were set to 28007905; 23359680; 29735986; 10048490
Hereditary ataxia with onset in adulthood v3.7 UCHL1 Sarah Leigh Publications for gene: UCHL1 were set to 23359680; 28007905; 29735986; 32656641
Adult onset hereditary spastic paraplegia v2.4 UCHL1 Sarah Leigh Publications for gene: UCHL1 were set to 23359680; 28007905; 29735986; 32656641
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.1 BCL11B Helen Lord changed review comment from: 36275064 Zhao et al, 2022, 25 month old Chinese boy with a novel fs variant in the BCL11B gene by WES and confirmed de novo by parental sanger sequencing c.2346_2361del. Patient shown to have frontal and right coronal synostosis on 3D-CT scan.
Table 1 - comparing the clinical features of the 6 patients with BCCLB variants reported in the literature with craniosynostosis. The other 5 identifed variants were all missense, 1 de novo and the other 4 inherited.
The truncation is predicted to lack the last three C2HH zinc finger domains (ZnF4-6). As BCL11B is a transcriptional activator, the premature stop-codon sequence of BCL11B may affect the proteins function in binding to it's target DNA and it's interactions with target proteins.

310673176 Goos et al, 2019 c.7C>A p.(Arg3Ser) de novo variant identified in a male patient with bicoronal synostosis, raised ICP, variant identified by WGS trio analysis.
Bcl11b is expressed in cranila sutures and Bcl11b-/- mice exhibit craniofacial abnormalities including craniosynostosis. Co immunoprecipitation analyses reveled that the amino acid substitrution abolished the ability of BCL11B to interact with both the NuRD and PRC2 complexes.
Crystal structures of RBBP4 in complex with the AA fragments of FOG-2, BCL11A and SALL4 showed that the motif residues Arg-3, Arg-4 and Lys-5 co-ordinated to the acidic core and surface of RBBP4, suggesting that the Arg-3 contributes to the ionic coordination, stabilising its interaction with RBBP4 and closely related RBBP7.
introduced the c.7C>A mutation into the germline of C57BL/6 mice using CRISPR-Cas9 genome editing. Het mice were born at Mendelian ratios survivied into adulthood without gross anatomical abnormalities and bred normally. However, examination of calvarial sutures by micro-CT revealed these mice exhibited variable and partial bilateral osteogenic fusion of the coronal suture that was accomponied by narrowing of the sagittal and lambdoid sutires by ~50% at P0. Other calvarial and facial sutures in these het mice were indistinguishable from those of wt mice. Hom mutant mice recapitulated perinatal lethality of Bcl11b-/- mice due to apparant respoiratiry insufficiency, as well as multisuture synostosis at P0 involving the coeronla (bilateral), interfrontal, sagittal, interparietal and temporal sutures; however, in marked contrast to Bcl11b-/-mice or those lacking BCL11B in cells derived from the neural crest, the Bcl11b R3S hom mice did not exhibit fusion of facial sutures.

34900871 Gaillard et al, 2021, 4 patients with BCL11B variants
Patient A: c.2000G>A p.(Gly667Glu) het left sided congernital diaphragmatic hernia (CDH) and progressive sagittal synostosis. Maternally inherited.
Patient B: c.1744G>A p.(Gly582Ser) het sagittal and bilambdoid synostosis. Paternally inherited.
Patient C: c.2018C>G p.(Pro673Arg) het left unicoronal synostosis. Maternally inherited.
Patient D: c.1265C>T p.(Pro422Leu) het sagittal synostosis. Maternally inherited.
Of notes the parents also carrying these variants were phenotypically normal; this could suggest incomplete penetrance, simialr to other craniosynostosis syndromes such as TCF12 and SMAD6.

36512050 Chaisrisawadisuk et al, 2022: 2 month old female with left coronal and sagittal synostosis on CT scan, found to have a de novo 14q32.12-q32.31 deletion (blood karyotpe and microarray) - the most likely candidate genes are YY1 and BCL11B for causing craniosynostosis in this patient.

36470856 Eto et al, 2022: 5 year old Japense boy - CT scan at 10 months revelaed partial early fusion of sagittal and lambda sutures - trio exome analysis identified a de novo het fs variant c.2439_2452dup p.(His818fs).

Case reported in Oxford Molecular genetics laboratory: 14q32.2 - 1.5Mb del: 14q32.2(99,052,763_100,591,634). Patient has unicoronal synostosis and intellectual disability - parental testing not yet undertaken.

4 cases of de novo BCL11B variants in patients with craniosynostosis, although for one of these patients two candidate genes that could be responsible for phenotype. 4 cases where missense variant inherited from an unaffected parents - suggests non-penetrance associated feature.
Sources: Expert list; to: 36275064 Zhao et al, 2022, 25 month old Chinese boy with a novel fs variant in the BCL11B gene by WES and confirmed de novo by parental sanger sequencing c.2346_2361del. Patient shown to have frontal and right coronal synostosis on 3D-CT scan.
Table 1 - comparing the clinical features of the 6 patients with BCCLB variants reported in the literature with craniosynostosis. The other 5 identifed variants were all missense, 1 de novo and the other 4 inherited.
The truncation is predicted to lack the last three C2HH zinc finger domains (ZnF4-6). As BCL11B is a transcriptional activator, the premature stop-codon sequence of BCL11B may affect the proteins function in binding to it's target DNA and it's interactions with target proteins.

31067316 Goos et al, 2019 c.7C>A p.(Arg3Ser) de novo variant identified in a male patient with bicoronal synostosis, raised ICP, variant identified by WGS trio analysis.
Bcl11b is expressed in cranila sutures and Bcl11b-/- mice exhibit craniofacial abnormalities including craniosynostosis. Co immunoprecipitation analyses reveled that the amino acid substitrution abolished the ability of BCL11B to interact with both the NuRD and PRC2 complexes.
Crystal structures of RBBP4 in complex with the AA fragments of FOG-2, BCL11A and SALL4 showed that the motif residues Arg-3, Arg-4 and Lys-5 co-ordinated to the acidic core and surface of RBBP4, suggesting that the Arg-3 contributes to the ionic coordination, stabilising its interaction with RBBP4 and closely related RBBP7.
introduced the c.7C>A mutation into the germline of C57BL/6 mice using CRISPR-Cas9 genome editing. Het mice were born at Mendelian ratios survivied into adulthood without gross anatomical abnormalities and bred normally. However, examination of calvarial sutures by micro-CT revealed these mice exhibited variable and partial bilateral osteogenic fusion of the coronal suture that was accomponied by narrowing of the sagittal and lambdoid sutires by ~50% at P0. Other calvarial and facial sutures in these het mice were indistinguishable from those of wt mice. Hom mutant mice recapitulated perinatal lethality of Bcl11b-/- mice due to apparant respoiratiry insufficiency, as well as multisuture synostosis at P0 involving the coeronla (bilateral), interfrontal, sagittal, interparietal and temporal sutures; however, in marked contrast to Bcl11b-/-mice or those lacking BCL11B in cells derived from the neural crest, the Bcl11b R3S hom mice did not exhibit fusion of facial sutures.

34900871 Gaillard et al, 2021, 4 patients with BCL11B variants
Patient A: c.2000G>A p.(Gly667Glu) het left sided congernital diaphragmatic hernia (CDH) and progressive sagittal synostosis. Maternally inherited.
Patient B: c.1744G>A p.(Gly582Ser) het sagittal and bilambdoid synostosis. Paternally inherited.
Patient C: c.2018C>G p.(Pro673Arg) het left unicoronal synostosis. Maternally inherited.
Patient D: c.1265C>T p.(Pro422Leu) het sagittal synostosis. Maternally inherited.
Of notes the parents also carrying these variants were phenotypically normal; this could suggest incomplete penetrance, simialr to other craniosynostosis syndromes such as TCF12 and SMAD6.

36512050 Chaisrisawadisuk et al, 2022: 2 month old female with left coronal and sagittal synostosis on CT scan, found to have a de novo 14q32.12-q32.31 deletion (blood karyotpe and microarray) - the most likely candidate genes are YY1 and BCL11B for causing craniosynostosis in this patient.

36470856 Eto et al, 2022: 5 year old Japense boy - CT scan at 10 months revelaed partial early fusion of sagittal and lambda sutures - trio exome analysis identified a de novo het fs variant c.2439_2452dup p.(His818fs).

Case reported in Oxford Molecular genetics laboratory: 14q32.2 - 1.5Mb del: 14q32.2(99,052,763_100,591,634). Patient has unicoronal synostosis and intellectual disability - parental testing not yet undertaken.

4 cases of de novo BCL11B variants in patients with craniosynostosis, although for one of these patients two candidate genes that could be responsible for phenotype. 4 cases where missense variant inherited from an unaffected parents - suggests non-penetrance associated feature.
Sources: Expert list
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.1 BCL11B Helen Lord gene: BCL11B was added
gene: BCL11B was added to Craniosynostosis. Sources: Expert list
Mode of inheritance for gene: BCL11B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: BCL11B were set to 36275064; 310673176; 34900871; 36512050; 36470856
Phenotypes for gene: BCL11B were set to Craniosynostosis and global developmental delay
Review for gene: BCL11B was set to GREEN
Added comment: 36275064 Zhao et al, 2022, 25 month old Chinese boy with a novel fs variant in the BCL11B gene by WES and confirmed de novo by parental sanger sequencing c.2346_2361del. Patient shown to have frontal and right coronal synostosis on 3D-CT scan.
Table 1 - comparing the clinical features of the 6 patients with BCCLB variants reported in the literature with craniosynostosis. The other 5 identifed variants were all missense, 1 de novo and the other 4 inherited.
The truncation is predicted to lack the last three C2HH zinc finger domains (ZnF4-6). As BCL11B is a transcriptional activator, the premature stop-codon sequence of BCL11B may affect the proteins function in binding to it's target DNA and it's interactions with target proteins.

310673176 Goos et al, 2019 c.7C>A p.(Arg3Ser) de novo variant identified in a male patient with bicoronal synostosis, raised ICP, variant identified by WGS trio analysis.
Bcl11b is expressed in cranila sutures and Bcl11b-/- mice exhibit craniofacial abnormalities including craniosynostosis. Co immunoprecipitation analyses reveled that the amino acid substitrution abolished the ability of BCL11B to interact with both the NuRD and PRC2 complexes.
Crystal structures of RBBP4 in complex with the AA fragments of FOG-2, BCL11A and SALL4 showed that the motif residues Arg-3, Arg-4 and Lys-5 co-ordinated to the acidic core and surface of RBBP4, suggesting that the Arg-3 contributes to the ionic coordination, stabilising its interaction with RBBP4 and closely related RBBP7.
introduced the c.7C>A mutation into the germline of C57BL/6 mice using CRISPR-Cas9 genome editing. Het mice were born at Mendelian ratios survivied into adulthood without gross anatomical abnormalities and bred normally. However, examination of calvarial sutures by micro-CT revealed these mice exhibited variable and partial bilateral osteogenic fusion of the coronal suture that was accomponied by narrowing of the sagittal and lambdoid sutires by ~50% at P0. Other calvarial and facial sutures in these het mice were indistinguishable from those of wt mice. Hom mutant mice recapitulated perinatal lethality of Bcl11b-/- mice due to apparant respoiratiry insufficiency, as well as multisuture synostosis at P0 involving the coeronla (bilateral), interfrontal, sagittal, interparietal and temporal sutures; however, in marked contrast to Bcl11b-/-mice or those lacking BCL11B in cells derived from the neural crest, the Bcl11b R3S hom mice did not exhibit fusion of facial sutures.

34900871 Gaillard et al, 2021, 4 patients with BCL11B variants
Patient A: c.2000G>A p.(Gly667Glu) het left sided congernital diaphragmatic hernia (CDH) and progressive sagittal synostosis. Maternally inherited.
Patient B: c.1744G>A p.(Gly582Ser) het sagittal and bilambdoid synostosis. Paternally inherited.
Patient C: c.2018C>G p.(Pro673Arg) het left unicoronal synostosis. Maternally inherited.
Patient D: c.1265C>T p.(Pro422Leu) het sagittal synostosis. Maternally inherited.
Of notes the parents also carrying these variants were phenotypically normal; this could suggest incomplete penetrance, simialr to other craniosynostosis syndromes such as TCF12 and SMAD6.

36512050 Chaisrisawadisuk et al, 2022: 2 month old female with left coronal and sagittal synostosis on CT scan, found to have a de novo 14q32.12-q32.31 deletion (blood karyotpe and microarray) - the most likely candidate genes are YY1 and BCL11B for causing craniosynostosis in this patient.

36470856 Eto et al, 2022: 5 year old Japense boy - CT scan at 10 months revelaed partial early fusion of sagittal and lambda sutures - trio exome analysis identified a de novo het fs variant c.2439_2452dup p.(His818fs).

Case reported in Oxford Molecular genetics laboratory: 14q32.2 - 1.5Mb del: 14q32.2(99,052,763_100,591,634). Patient has unicoronal synostosis and intellectual disability - parental testing not yet undertaken.

4 cases of de novo BCL11B variants in patients with craniosynostosis, although for one of these patients two candidate genes that could be responsible for phenotype. 4 cases where missense variant inherited from an unaffected parents - suggests non-penetrance associated feature.
Sources: Expert list
Li Fraumeni Syndrome v0.4 Eleanor Williams Panel status changed from internal to public
Panel types changed to
Hereditary diffuse gastric cancer v0.4 Eleanor Williams Panel status changed from internal to public
Panel types changed to
Autoimmune lymphoproliferative syndrome with defective apoptosis v0.4 Eleanor Williams Panel status changed from internal to public
Panel types changed to
Ataxia telangiectasia - mutation testing v0.5 Eleanor Williams Panel status changed from internal to public
Ataxia telangiectasia - mutation testing v0.4 Eleanor Williams Panel types changed to
APC associated Polyposis v0.6 Eleanor Williams Panel status changed from internal to public
Panel types changed to
Alveolar capillary dysplasia with misalignment of pulmonary veins v0.4 Eleanor Williams Panel status changed from internal to public
Panel types changed to
Alstrom syndrome v0.4 Eleanor Williams Panel status changed from internal to public
Panel types changed to
Albright hereditary osteodystrophy, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, acrodysostosis and osteoma cutis v0.5 Eleanor Williams Panel status changed from internal to public
Panel types changed to
Agammaglobulinaemia with absent BTK expression v0.5 Eleanor Williams Panel status changed from internal to public
Panel types changed to
Acute intermittent porphyria v0.5 Eleanor Williams Panel status changed from internal to public
Panel types changed to
Li Fraumeni Syndrome v0.3 TP53 Eleanor Williams reviewed gene: TP53: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Li Fraumeni Syndrome v0.2 TP53 Eleanor Williams gene: TP53 was added
gene: TP53 was added to Li Fraumeni Syndrome. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: TP53 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Li Fraumeni Syndrome v0.1 Eleanor Williams Panel types changed to GMS Rare Disease
Hereditary diffuse gastric cancer v0.3 CDH1 Eleanor Williams reviewed gene: CDH1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary diffuse gastric cancer v0.2 CDH1 Eleanor Williams gene: CDH1 was added
gene: CDH1 was added to CDH1-related cancer syndrome. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: CDH1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary diffuse gastric cancer v0.1 Eleanor Williams Panel types changed to GMS Rare Disease
Autoimmune lymphoproliferative syndrome with defective apoptosis v0.3 FAS Eleanor Williams reviewed gene: FAS: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Autoimmune lymphoproliferative syndrome with defective apoptosis v0.2 FAS Eleanor Williams gene: FAS was added
gene: FAS was added to Autoimmune lymphoproliferative syndrome with defective apoptosis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: FAS was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Autoimmune lymphoproliferative syndrome with defective apoptosis v0.1 Eleanor Williams Panel types changed to GMS Rare Disease
APC associated Polyposis v0.5 APC Eleanor Williams changed review comment from: APC has been added to the panel for R414 APC associated Polyposis with a green rating as agreed with the NHS Genomic Medicine Service.; to: APC has been added to the panel for the clinical indication 'R414 APC associated Polyposis' with a green rating as agreed with the NHS Genomic Medicine Service.
Alveolar capillary dysplasia with misalignment of pulmonary veins v0.3 FOXF1 Eleanor Williams changed review comment from: FOXF1 has been added to the panel for R330 Alveolar capillary dysplasia with misalignment of pulmonary veins with a green rating as agreed with the NHS Genomic Medicine Service.; to: FOXF1 has been added to the panel for the clinical indication 'R330 Alveolar capillary dysplasia with misalignment of pulmonary veins' with a green rating as agreed with the NHS Genomic Medicine Service.
Alstrom syndrome v0.3 ALMS1 Eleanor Williams changed review comment from: ALMS1 has been added to the panel for R106 Alstrom syndrome with a green rating as agreed with the NHS Genomic Medicine Service.; to: ALMS1 has been added to the panel for the clinical indication 'R106 Alstrom syndrome' with a green rating as agreed with the NHS Genomic Medicine Service.
Albright hereditary osteodystrophy, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, acrodysostosis and osteoma cutis v0.4 PRKAR1A Eleanor Williams changed review comment from: PRKAR1A has been added to the panel for R293 Albright hereditary osteodystrophy, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, acrodysostosis and osteoma cutis with a green rating as agreed with the NHS Genomic Medicine Service.; to: PRKAR1A has been added to the panel for the clinical indication 'R293 Albright hereditary osteodystrophy, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, acrodysostosis and osteoma cutis' with a green rating as agreed with the NHS Genomic Medicine Service.
Albright hereditary osteodystrophy, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, acrodysostosis and osteoma cutis v0.4 PDE4D Eleanor Williams changed review comment from: PDE4D has been added to the panel for R293 Albright hereditary osteodystrophy, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, acrodysostosis and osteoma cutis with a green rating as agreed with the NHS Genomic Medicine Service.; to: PDE4D has been added to the panel for the clinical indication 'R293 Albright hereditary osteodystrophy, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, acrodysostosis and osteoma cutis' with a green rating as agreed with the NHS Genomic Medicine Service.
Albright hereditary osteodystrophy, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, acrodysostosis and osteoma cutis v0.4 GNAS Eleanor Williams changed review comment from: GNAS has been added to the panel for R293 Albright hereditary osteodystrophy, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, acrodysostosis and osteoma cutis with a green rating as agreed with the NHS Genomic Medicine Service.; to: GNAS has been added to the panel for the clinical indication 'R293 Albright hereditary osteodystrophy, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, acrodysostosis and osteoma cutis' with a green rating as agreed with the NHS Genomic Medicine Service.
Agammaglobulinaemia with absent BTK expression v0.4 BTK Eleanor Williams changed review comment from: BTK has been added to the panel for R233 Agammaglobulinaemia with absent BTK expression with a green rating as agreed with the NHS Genomic Medicine Service.; to: BTK has been added to the panel for the clinical indication 'R233 Agammaglobulinaemia with absent BTK expression' with a green rating as agreed with the NHS Genomic Medicine Service.
Ataxia telangiectasia - mutation testing v0.3 ATM Eleanor Williams reviewed gene: ATM: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia telangiectasia - mutation testing v0.2 ATM Eleanor Williams gene: ATM was added
gene: ATM was added to Ataxia telangiectasia - mutation testing. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: ATM was set to BIALLELIC, autosomal or pseudoautosomal
Ataxia telangiectasia - mutation testing v0.1 Eleanor Williams Panel types changed to GMS Rare Disease
APC associated Polyposis v0.5 APC Eleanor Williams reviewed gene: APC: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
APC associated Polyposis v0.4 APC Eleanor Williams gene: APC was added
gene: APC was added to APC associated Polyposis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: APC was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
APC associated Polyposis v0.1 Eleanor Williams Panel types changed to GMS Rare Disease
Alveolar capillary dysplasia with misalignment of pulmonary veins v0.3 FOXF1 Eleanor Williams reviewed gene: FOXF1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Alveolar capillary dysplasia with misalignment of pulmonary veins v0.2 FOXF1 Eleanor Williams gene: FOXF1 was added
gene: FOXF1 was added to Alveolar capillary dysplasia with misalignment of pulmonary veins. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: FOXF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Alveolar capillary dysplasia with misalignment of pulmonary veins v0.1 Eleanor Williams Panel types changed to GMS Rare Disease
Alstrom syndrome v0.3 ALMS1 Eleanor Williams reviewed gene: ALMS1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Alstrom syndrome v0.2 ALMS1 Eleanor Williams gene: ALMS1 was added
gene: ALMS1 was added to Alstrom syndrome. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: ALMS1 was set to BIALLELIC, autosomal or pseudoautosomal
Alstrom syndrome v0.1 Eleanor Williams Panel types changed to GMS Rare Disease
Albright hereditary osteodystrophy, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, acrodysostosis and osteoma cutis v0.3 PRKAR1A Eleanor Williams reviewed gene: PRKAR1A: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Albright hereditary osteodystrophy, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, acrodysostosis and osteoma cutis v0.3 PDE4D Eleanor Williams reviewed gene: PDE4D: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Albright hereditary osteodystrophy, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, acrodysostosis and osteoma cutis v0.3 GNAS Eleanor Williams reviewed gene: GNAS: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Albright hereditary osteodystrophy, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, acrodysostosis and osteoma cutis v0.2 PRKAR1A Eleanor Williams gene: PRKAR1A was added
gene: PRKAR1A was added to Albright hereditary osteodystrophy, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, acrodysostosis and osteoma cutis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: PRKAR1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Albright hereditary osteodystrophy, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, acrodysostosis and osteoma cutis v0.2 PDE4D Eleanor Williams gene: PDE4D was added
gene: PDE4D was added to Albright hereditary osteodystrophy, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, acrodysostosis and osteoma cutis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: PDE4D was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Albright hereditary osteodystrophy, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, acrodysostosis and osteoma cutis v0.2 GNAS Eleanor Williams gene: GNAS was added
gene: GNAS was added to Albright hereditary osteodystrophy, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, acrodysostosis and osteoma cutis. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: GNAS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Albright hereditary osteodystrophy, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, acrodysostosis and osteoma cutis v0.1 Eleanor Williams Panel types changed to GMS Rare Disease
Acute intermittent porphyria v0.4 HMBS Eleanor Williams edited their review of gene: HMBS: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Acute intermittent porphyria v0.4 HMBS Eleanor Williams changed review comment from: This gene has been added to the panel for R169 Acute intermittent porphyria with a green rating as agreed with the NHS Genomic Medicine Service.; to: HMBS has been added to the panel for R169 Acute intermittent porphyria with a green rating as agreed with the NHS Genomic Medicine Service.
Agammaglobulinaemia with absent BTK expression v0.4 BTK Eleanor Williams reviewed gene: BTK: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Agammaglobulinaemia with absent BTK expression v0.3 BTK Eleanor Williams gene: BTK was added
gene: BTK was added to Agammaglobulinaemia with absent BTK expression. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: BTK was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Agammaglobulinaemia with absent BTK expression v0.1 Eleanor Williams Panel types changed to GMS Rare Disease
Acute intermittent porphyria v0.4 HMBS Eleanor Williams commented on gene: HMBS
Acute intermittent porphyria v0.3 HMBS Eleanor Williams gene: HMBS was added
gene: HMBS was added to Acute intermittent porphyria. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: HMBS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary ataxia v1.313 UCHL1 Samuel McCall reviewed gene: UCHL1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35986737; Phenotypes: spasticity, ataxia, neuropathy, optic atrophy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Current diagnostic: yes
Congenital disorders of glycosylation v3.2 ST3GAL3 Arina Puzriakova Classified gene: ST3GAL3 as Amber List (moderate evidence)
Congenital disorders of glycosylation v3.2 ST3GAL3 Arina Puzriakova Added comment: Comment on list classification: This gene should be promoted to Green at the next GMS panel update. Sufficient cases (>3) to support a gene-disease association (PMID: 21907012; 23252400; 31584066). This gene is also green on the IEM panel (v3.0) and as such should be reflected on this panel.

ST3GAL3 encodes the β-galactoside-α2,3-sialyltransferase-III (ST3Gal-III), which in humans predominantly forms the sialyl Lewis a (sLe a) epitope on glycoproteins.
Congenital disorders of glycosylation v3.2 ST3GAL3 Arina Puzriakova Gene: st3gal3 has been classified as Amber List (Moderate Evidence).
Congenital disorders of glycosylation v3.1 ST3GAL3 Arina Puzriakova Tag Q1_23_promote_green tag was added to gene: ST3GAL3.
Acute intermittent porphyria v0.1 Eleanor Williams Panel types changed to GMS Rare Disease
Li Fraumeni Syndrome v0.0 Eleanor Williams Added Panel Li Fraumeni Syndrome
Set list of related panels to R216
Hereditary diffuse gastric cancer v0.0 Eleanor Williams Added Panel CDH1-related cancer syndrome
Set list of related panels to R215
Adult onset neurodegenerative disorder v3.47 CST3 Achchuthan Shanmugasundram changed review comment from: There are >3 unrelated cases with relevant phenotype (cerebral amyloid angiopathy) and age of onset is third or fourth decade of life. However, all these cases were identified with the same heterozygous variant in the CST3 gene (p.L68Q) and was from the same Icelandic population. This gene should be rated AMBER in the absence of functional studies on this specific variant, de novo cases with this variant from other populations or existence of other variants causing the same phenotype.; to: There are >3 unrelated cases with relevant phenotype (cerebral amyloid angiopathy) and age of onset is third or fourth decade of life. However, all these cases were identified with the same heterozygous variant in the CST3 gene (p.L68Q) and was from the same Icelandic population. There should be functional studies on this specific variant, de novo cases with this variant from other populations or existence of other variants causing the same phenotype for it to be rated green. Hence, this gene is rated AMBER.
Adult onset neurodegenerative disorder v3.47 CST3 Achchuthan Shanmugasundram Deleted their comment
Adult onset neurodegenerative disorder v3.47 CST3 Achchuthan Shanmugasundram edited their review of gene: CST3: Added comment: There are >3 unrelated cases with relevant phenotype (cerebral amyloid angiopathy) and age of onset is third or fourth decade of life. However, all these cases were identified with the same heterozygous variant in the CST3 gene (p.L68Q) and was from the same Icelandic population. This gene should be rated AMBER in the absence of functional studies on this specific variant, de novo cases with this variant from other populations or existence of other variants causing the same phenotype.; Changed rating: AMBER
Adult onset neurodegenerative disorder v3.47 CST3 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: CST3.
Adult onset leukodystrophy v2.44 LAMB1 Sarah Leigh edited their review of gene: LAMB1: Added comment: PMID: 34606115 reports heterozygous end-truncated LAMB1 in a hippocampal memory defect and a leukoencephalopathy. Other publications (PMID: 32548278; 25925986;23472759;29888467),
OMIM (https://www.omim.org/entry/150240?search=LAMB1&highlight=lamb1#geneMap), Gen2Phen (https://www.ebi.ac.uk/gene2phenotype/gfd?dbID=1439) and ClinGen (https://search.clinicalgenome.org/kb/genes/HGNC:6486) all report the a bialleic mode inheritance between LAMB1 variants and disease. Based on this discrepancy, the suggested mode of inheritance has been changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Adult onset leukodystrophy v2.44 LAMB1 Sarah Leigh Tag Q1_23_MOI tag was added to gene: LAMB1.
Intellectual disability v4.42 PAN2 Sarah Leigh edited their review of gene: PAN2: Added comment: PAN2 is not associated with a phenotype in OMIM, but has a moderate association with PAN2-related neurodevelopmental disorder with multiple congenital anomalies in Gen2Phen. PMID: 29620724 reports one homozygous variant in one case and PMID: 35304602 reports a further three homozygous variants in three unrelated cases. It would appear that the syndrome associated with PAN2 variants has multiple congenital anomalies (PMID: 35304602, table 1), including intellectual disabilty ranging from mild to global developmental delay.; Changed rating: GREEN
Intellectual disability v4.42 PAN2 Sarah Leigh Tag Q1_23_promote_green tag was added to gene: PAN2.
Intellectual disability v4.42 PAN2 Sarah Leigh Classified gene: PAN2 as Amber List (moderate evidence)
Intellectual disability v4.42 PAN2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v4.42 PAN2 Sarah Leigh Gene: pan2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.41 PAN2 Sarah Leigh Publications for gene: PAN2 were set to 29620724; https://doi.org/10.1038/s41431-022-01077-y
Intellectual disability v4.40 HIST1H4D Sarah Leigh commented on gene: HIST1H4D: HIST1H4D is the previous symbol for H4 clustered histone 4 with the approved symbol: H4C4 (https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:4782).
Intellectual disability v4.40 HIST1H4D Sarah Leigh Classified gene: HIST1H4D as Red List (low evidence)
Intellectual disability v4.40 HIST1H4D Sarah Leigh Gene: hist1h4d has been classified as Red List (Low Evidence).
Intellectual disability v4.39 HIST1H4D Sarah Leigh Tag new-gene-name tag was added to gene: HIST1H4D.
Intellectual disability v4.39 HIST1H4D Sarah Leigh reviewed gene: HIST1H4D: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v4.39 HIST1H4F Sarah Leigh Classified gene: HIST1H4F as Red List (low evidence)
Intellectual disability v4.39 HIST1H4F Sarah Leigh Gene: hist1h4f has been classified as Red List (Low Evidence).
Intellectual disability v4.38 HIST1H4F Sarah Leigh edited their review of gene: HIST1H4F: Added comment: H4C6 is not associated with a phenotype in OMIM or Gen2Phen. PMID: 35202563 reports single H4C6 variant in a case with a neurodevelopmental syndrome, based on functional studies, the authors suggest that the variant does not have a loss of function action.; Changed rating: RED
Intellectual disability v4.38 HIST1H4F Sarah Leigh commented on gene: HIST1H4F
Intellectual disability v4.38 HIST1H4F Sarah Leigh Tag new-gene-name tag was added to gene: HIST1H4F.
Intellectual disability v4.38 HIST1H4I Sarah Leigh commented on gene: HIST1H4I: Associated with Tessadori-van Haaften neurodevelopmental syndrome 4, (OMIM:619951), but not with a phenotype in Gen2Phen. PMID: 35202563 reports two H4C9 variants in two patients with a neurodevelopmental syndrome, based on functional studies, the authors suggest that the variants do not have a loss of function action.
Intellectual disability v4.38 HIST1H4I Sarah Leigh Classified gene: HIST1H4I as Amber List (moderate evidence)
Intellectual disability v4.38 HIST1H4I Sarah Leigh Gene: hist1h4i has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.37 HIST1H4I Sarah Leigh Phenotypes for gene: HIST1H4I were changed from Global developmental delay; Intellectual disability; Microcephaly; Growth abnormality; Abnormality of the face to Tessadori-van Haaften neurodevelopmental syndrome 4, OMIM:619951; Tessadori-Van Haaften neurodevelopmental syndrome 4, MONDO:0031000
Intellectual disability v4.36 HIST1H4I Sarah Leigh commented on gene: HIST1H4I
Intellectual disability v4.36 HIST1H4I Sarah Leigh Tag new-gene-name tag was added to gene: HIST1H4I.
Intellectual disability v4.36 HIST1H4E Sarah Leigh Tag Q1_23_promote_green tag was added to gene: HIST1H4E.
Intellectual disability v4.36 HIST1H4E Sarah Leigh edited their review of gene: HIST1H4E: Added comment: Associated with in Tessadori-van Haaften neurodevelopmental syndrome 3 (OMIM:619950), but not with a phenotype in Gen2Phen. PMID: 35202563 reports seven H4C5 variants in 17 patients with a neurodevelopmental syndrome, based on functional studies, the authors suggest that the variants do not have a loss of function action.; Changed rating: GREEN
Intellectual disability v4.36 HIST1H4E Sarah Leigh Classified gene: HIST1H4E as Amber List (moderate evidence)
Intellectual disability v4.36 HIST1H4E Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v4.36 HIST1H4E Sarah Leigh Gene: hist1h4e has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.35 HIST1H4E Sarah Leigh commented on gene: HIST1H4E
Intellectual disability v4.35 HIST1H4E Sarah Leigh Tag new-gene-name tag was added to gene: HIST1H4E.
Intellectual disability v4.35 HIST1H4E Sarah Leigh Phenotypes for gene: HIST1H4E were changed from Global developmental delay; Intellectual disability; Microcephaly; Growth abnormality; Abnormality of the face to Tessadori-van Haaften neurodevelopmental syndrome 3, OMIM:619950; Tessadori-Van Haaften neurodevelopmental syndrome 3 MONDO:0030993
Early onset or syndromic epilepsy v3.19 CUX2 Sarah Leigh Tag Q1_23_MOI tag was added to gene: CUX2.
Tag Q1_23_NHS_review tag was added to gene: CUX2.
Early onset or syndromic epilepsy v3.19 CUX2 Sarah Leigh edited their review of gene: CUX2: Added comment: It is recommended that the mode of inheritance of CUX2 is changed from:
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted, based on the review by Tracy Lester (Genetics laboratory, Oxford UK)(14 Nov 2022).; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.34 ZNF292 Sarah Leigh edited their review of gene: ZNF292: Added comment: Associated with relevant phenotype in OMIM and as strong Gen2Phen gene. At least seven autosomal dominant or de novo ZNF292 variants have been reported in at least eleven unrelated cases of Intellectual developmental disorder, autosomal dominant 64 (OMIM: 619188)(PMID: 31723249).; Changed rating: GREEN
Intellectual disability v4.34 ZNF292 Sarah Leigh Classified gene: ZNF292 as Amber List (moderate evidence)
Intellectual disability v4.34 ZNF292 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v4.34 ZNF292 Sarah Leigh Gene: znf292 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.33 ZNF292 Sarah Leigh Tag Q1_23_promote_green tag was added to gene: ZNF292.
Tag Q1_23_NHS_review tag was added to gene: ZNF292.
Intellectual disability v4.33 ZNF292 Sarah Leigh Phenotypes for gene: ZNF292 were changed from Intellectual disability; Autism; Attention deficit hyperactivity disorder; Abnormality of the face; Abnormal muscle tone; Abnormality of nervous system morphology; Growth abnormality; Feeding difficulties; Abnormality of the skeletal system; Abnormality of the cardiovascular system; Microcephaly; Seizures to Intellectual developmental disorder, autosomal dominant 64, OMIM:619188; intellectual developmental disorder, autosomal dominant 64, MONDO:0030934
Intellectual disability v4.32 PAX6 Sarah Leigh Tag Q1_23_demote_red tag was added to gene: PAX6.
Tag Q1_23_NHS_review tag was added to gene: PAX6.
Intellectual disability v4.32 PAX6 Sarah Leigh reviewed gene: PAX6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Congenital myopathy v3.12 KY Sarah Leigh Classified gene: KY as Amber List (moderate evidence)
Congenital myopathy v3.12 KY Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Congenital myopathy v3.12 KY Sarah Leigh Gene: ky has been classified as Amber List (Moderate Evidence).
Congenital myopathy v3.11 KY Sarah Leigh Tag Q1_23_promote_green tag was added to gene: KY.
Tag Q1_23_NHS_review tag was added to gene: KY.
Congenital muscular dystrophy v3.20 DPM3 Sarah Leigh Deleted their comment
Congenital muscular dystrophy v3.20 DPM3 Sarah Leigh Classified gene: DPM3 as Amber List (moderate evidence)
Congenital muscular dystrophy v3.20 DPM3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Congenital muscular dystrophy v3.20 DPM3 Sarah Leigh Gene: dpm3 has been classified as Amber List (Moderate Evidence).
Congenital muscular dystrophy v3.19 DPM3 Sarah Leigh Tag Q1_23_promote_green tag was added to gene: DPM3.
Tag Q1_23_NHS_review tag was added to gene: DPM3.
Congenital muscular dystrophy v3.19 DPM3 Sarah Leigh edited their review of gene: DPM3: Added comment: A green rating has been recommended based on the review from Anna Sarkozy (Great Ormond Street Hospital)(10 Nov 2022) and consultation with Helen Brittain (Clinical Fellow, Genomics England).; Changed rating: GREEN
Congenital muscular dystrophy v3.19 DPM3 Sarah Leigh Classified gene: DPM3 as Amber List (moderate evidence)
Congenital muscular dystrophy v3.19 DPM3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Congenital muscular dystrophy v3.19 DPM3 Sarah Leigh Gene: dpm3 has been classified as Amber List (Moderate Evidence).
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.4 DPM3 Sarah Leigh Phenotypes for gene: DPM3 were changed from Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 15, 612937; limb-girdle muscular dystrophy; dystroglycanopathy to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 15, OMIM:612937; DPM3-congenital disorder of glycosylation, MONDO:0013049; ?Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 15, OMIM:618992; muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type b, 15, MONDO:0033556
Congenital muscular dystrophy v3.18 DPM3 Sarah Leigh Phenotypes for gene: DPM3 were changed from congenital muscular dystrophies; Congenital disorder of glycosylation, type Io, 612937'Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 15, 612937 to Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 15, OMIM:612937; DPM3-congenital disorder of glycosylation, MONDO:0013049; ?Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 15, OMIM:618992; muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type b, 15, MONDO:0033556
Intellectual disability v4.32 ZNF292 Ian Berry reviewed gene: ZNF292: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31723249; Phenotypes: Intellectual disability, mild, ASD; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Retinal disorders v3.24 POMGNT2 Achchuthan Shanmugasundram Phenotypes for gene: POMGNT2 were changed from to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 8, OMIM:614830
Retinal disorders v3.23 POMGNT2 Achchuthan Shanmugasundram Publications for gene: POMGNT2 were set to
Retinal disorders v3.22 POMGNT2 Achchuthan Shanmugasundram Mode of inheritance for gene: POMGNT2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v3.21 POMGNT2 Achchuthan Shanmugasundram Classified gene: POMGNT2 as Amber List (moderate evidence)
Retinal disorders v3.21 POMGNT2 Achchuthan Shanmugasundram Gene: pomgnt2 has been classified as Amber List (Moderate Evidence).
Retinal disorders v3.20 POMGNT2 Achchuthan Shanmugasundram reviewed gene: POMGNT2: Rating: AMBER; Mode of pathogenicity: None; Publications: 22958903, 27066570; Phenotypes: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 8, OMIM:614830; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v3.20 STN1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: STN1.
Retinal disorders v3.20 STN1 Achchuthan Shanmugasundram Phenotypes for gene: STN1 were changed from to Cerebroretinal microangiopathy with calcifications and cysts 2, OMIM:617341
Retinal disorders v3.19 STN1 Achchuthan Shanmugasundram Publications for gene: STN1 were set to
Retinal disorders v3.18 STN1 Achchuthan Shanmugasundram Mode of inheritance for gene: STN1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v3.17 STN1 Achchuthan Shanmugasundram Classified gene: STN1 as Amber List (moderate evidence)
Retinal disorders v3.17 STN1 Achchuthan Shanmugasundram Gene: stn1 has been classified as Amber List (Moderate Evidence).
Retinal disorders v3.16 STN1 Achchuthan Shanmugasundram changed review comment from: Comment on classification: Four unrelated patients identified with biallelic variants (homozygous or compound heterozygous) have been reported with retinal telangiectasia/ retinal lesions (PMID:27432940, PMID:34110109). hence, this gene can be rated GREEN.; to: Comment on classification: Four unrelated patients identified with biallelic variants (homozygous or compound heterozygous) have been reported with retinal telangiectasia/ retinal lesions (PMID:27432940, PMID:34110109). I would therefore recommend this gene to be rated GREEN at the next GMS review.
Retinal disorders v3.16 STN1 Achchuthan Shanmugasundram reviewed gene: STN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27432940, 34110109; Phenotypes: Cerebroretinal microangiopathy with calcifications and cysts 2, OMIM:617341; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v3.16 COL11A1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: COL11A1.
Tag Q1_23_expert_review tag was added to gene: COL11A1.
Retinal disorders v3.16 COL11A1 Achchuthan Shanmugasundram Phenotypes for gene: COL11A1 were changed from Stickler syndrome, type II, OMIM:604841 to Stickler syndrome, type II, OMIM:604841; Marshall syndrome, OMIM:154780
Retinal disorders v3.15 COL11A1 Achchuthan Shanmugasundram Publications for gene: COL11A1 were set to
Retinal disorders v3.14 COL11A1 Achchuthan Shanmugasundram Mode of inheritance for gene: COL11A1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Retinal disorders v3.13 COL11A1 Achchuthan Shanmugasundram reviewed gene: COL11A1: Rating: ; Mode of pathogenicity: None; Publications: 10486316, 17318849; Phenotypes: Marshall syndrome, OMIM:154780, Stickler syndrome, type II, OMIM:604841; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Retinal disorders v3.13 COL9A3 Achchuthan Shanmugasundram Tag Q1_23_expert_review tag was added to gene: COL9A3.
Retinal disorders v3.13 COL9A3 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: COL9A3.
Retinal disorders v3.13 COL9A3 Achchuthan Shanmugasundram Phenotypes for gene: COL9A3 were changed from to Stickler syndrome, type VI, OMIM:620022
Retinal disorders v3.12 COL9A3 Achchuthan Shanmugasundram Publications for gene: COL9A3 were set to
Retinal disorders v3.11 COL9A3 Achchuthan Shanmugasundram Mode of inheritance for gene: COL9A3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v3.10 COL9A3 Achchuthan Shanmugasundram edited their review of gene: COL9A3: Changed publications to: 30450842, 33570243, 33633367
Retinal disorders v3.10 COL9A3 Achchuthan Shanmugasundram reviewed gene: COL9A3: Rating: ; Mode of pathogenicity: None; Publications: 33633367; Phenotypes: Stickler syndrome, type VI, OMIM:620022; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v3.2 IKZF2 Dmitrijs Rots reviewed gene: IKZF2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34826260, 34920454; Phenotypes: Immunodeficiency; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v3.21 DMXL2 Dmitrijs Rots reviewed gene: DMXL2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary ataxia v1.313 DMXL2 Dmitrijs Rots reviewed gene: DMXL2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary neuropathy or pain disorder v2.7 MYH14 Dmitrijs Rots reviewed gene: MYH14: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 31231018; Phenotypes: Neuropathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy v1.457 MYH14 Dmitrijs Rots reviewed gene: MYH14: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 31231018; Phenotypes: Neuropathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v3.10 COL9A2 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: COL9A2.
Tag Q1_23_expert_review tag was added to gene: COL9A2.
Retinal disorders v3.10 COL9A2 Achchuthan Shanmugasundram Publications for gene: COL9A2 were set to
Retinal disorders v3.9 COL9A2 Achchuthan Shanmugasundram reviewed gene: COL9A2: Rating: ; Mode of pathogenicity: None; Publications: 21671392, 31090205, 33356723; Phenotypes: Stickler syndrome, type V, OMIM:614284; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v3.9 COL9A1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: COL9A1.
Tag Q1_23_expert_review tag was added to gene: COL9A1.
Retinal disorders v3.9 COL9A1 Achchuthan Shanmugasundram Publications for gene: COL9A1 were set to
Retinal disorders v3.8 COL9A1 Achchuthan Shanmugasundram reviewed gene: COL9A1: Rating: ; Mode of pathogenicity: None; Publications: 16909383, 21421862; Phenotypes: Stickler syndrome, type IV, OMIM:614134; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v3.8 COL2A1 Achchuthan Shanmugasundram changed review comment from: There is sufficient evidence linking COL2A1 with retinal disorders (retinal thinning, lattice retinopathy, retinal detachment, vitreoretinal degeneration, blindness etc). However, these phenotypes overlap with that of Stickler syndrome and this gene is green on Stickler syndrome panel. It has previously been decided (2019) in consultation with Gavin Arno (UCL Institute of Ophthalmology/Moorfields Eye Hospital) that this gene can stay red in this panel. Given this gene has recently been proposed for this panel by an expert, I am recommending that the Test Evaluation Working Group review and define the panel scope, and reach consensus as to whether this gene is appropriate for inclusion.; to: There is sufficient evidence linking COL2A1 with retinal disorders (retinal thinning, lattice retinopathy, retinal detachment, vitreoretinal degeneration, blindness etc). However, these phenotypes overlap with that of Stickler syndrome and this gene is green on Stickler syndrome panel (https://panelapp.genomicsengland.co.uk/panels/3/gene/COL2A1/). It has previously been decided (2019) in consultation with Gavin Arno (UCL Institute of Ophthalmology/Moorfields Eye Hospital) that this gene can stay red in this panel. Given this gene has recently been proposed for this panel by an expert, I am recommending that the Test Evaluation Working Group review and define the panel scope, and reach consensus as to whether this gene is appropriate for inclusion.
Retinal disorders v3.8 COL2A1 Achchuthan Shanmugasundram Phenotypes for gene: COL2A1 were changed from Eye Disorders to Epiphyseal dysplasia, multiple, with myopia and deafness, OMIM:132450; Vitreoretinopathy with phalangeal epiphyseal dysplasia, OMIM:619248; Kniest dysplasia, OMIM:156550; SED congenita, OMIM:183900; Stickler syndrome, type I, OMIM:108300; Stickler syndrome, type I, nonsyndromic ocular, OMIM:609508
Retinal disorders v3.7 COL2A1 Achchuthan Shanmugasundram Mode of inheritance for gene: COL2A1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v3.6 COL2A1 Achchuthan Shanmugasundram reviewed gene: COL2A1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Epiphyseal dysplasia, multiple, with myopia and deafness, OMIM:132450, Vitreoretinopathy with phalangeal epiphyseal dysplasia, OMIM:619248, Kniest dysplasia, OMIM:156550, SED congenita, OMIM:183900, Stickler syndrome, type I, OMIM:108300, Stickler syndrome, type I, nonsyndromic ocular, OMIM:609508; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.32 KDM6A Arina Puzriakova Phenotypes for gene: KDM6A were changed from Kabuki syndrome 2, 300867; Kabuki syndrome; KABUKI SYNDROME 2; KABUK2 to Kabuki syndrome 2, OMIM:300867
Adult onset leukodystrophy v2.44 TTR Sarah Leigh edited their review of gene: TTR: Added comment: Associated with Amyloidosis, hereditary, transthyretin-related (OMIM:105210), but not associated with a phenotype in Gen2Phen. Numerous TTR variants have been reported in cases from different populations.; Changed rating: GREEN
Adult onset leukodystrophy v2.44 TTR Sarah Leigh Classified gene: TTR as Amber List (moderate evidence)
Adult onset leukodystrophy v2.44 TTR Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Adult onset leukodystrophy v2.44 TTR Sarah Leigh Gene: ttr has been classified as Amber List (Moderate Evidence).
Adult onset leukodystrophy v2.43 TTR Sarah Leigh Tag Q1_23_promote_green tag was added to gene: TTR.
Tag Q1_23_NHS_review tag was added to gene: TTR.
Adult onset leukodystrophy v2.43 TTR Sarah Leigh Mode of inheritance for gene: TTR was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset leukodystrophy v2.42 TTR Sarah Leigh Phenotypes for gene: TTR were changed from to Amyloidosis, hereditary, transthyretin-related, OMIM:105210; familial amyloid neuropathy, MONDO:0007100
Adult onset leukodystrophy v2.41 TTR Sarah Leigh Publications for gene: TTR were set to
Adult onset neurodegenerative disorder v3.47 LAMB1 Sarah Leigh Publications for gene: LAMB1 were set to 32548278; 34606115
Adult onset leukodystrophy v2.40 LAMB1 Sarah Leigh Publications for gene: LAMB1 were set to 32548278; 34606115; 23472759; 25925986
Inherited white matter disorders v1.169 LAMB1 Sarah Leigh Publications for gene: LAMB1 were set to 23472759; 25925986; 29888467
Adult onset leukodystrophy v2.39 LAMB1 Sarah Leigh Publications for gene: LAMB1 were set to 32548278; 34606115
Adult onset leukodystrophy v2.38 LAMB1 Sarah Leigh edited their review of gene: LAMB1: Added comment: Associated with relevant phenotype in OMIM and as strong Gen2Phen gene. At least four variants have been reported in three unrelated cases of Lissencephaly 5, (OMIM:615191).; Changed rating: GREEN
Adult onset leukodystrophy v2.38 LAMB1 Sarah Leigh Classified gene: LAMB1 as Amber List (moderate evidence)
Adult onset leukodystrophy v2.38 LAMB1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Adult onset leukodystrophy v2.38 LAMB1 Sarah Leigh Gene: lamb1 has been classified as Amber List (Moderate Evidence).
Adult onset leukodystrophy v2.37 LAMB1 Sarah Leigh Tag Q1_23_promote_green tag was added to gene: LAMB1.
Tag Q1_23_NHS_review tag was added to gene: LAMB1.
Adult onset neurodegenerative disorder v3.46 LAMB1 Sarah Leigh Publications for gene: LAMB1 were set to
Adult onset leukodystrophy v2.37 LAMB1 Sarah Leigh Phenotypes for gene: LAMB1 were changed from Retinal Vascular Abnormality; mild intellectual disability; white matter lesions; lower limb spasticity to Lissencephaly 5, OMIM:615191; cobblestone lissencephaly without muscular or ocular involvement, MONDO:0014077
Adult onset neurodegenerative disorder v3.45 LAMB1 Sarah Leigh Phenotypes for gene: LAMB1 were changed from Lissencephaly 5, OMIM:615191 to Lissencephaly 5, OMIM:615191; cobblestone lissencephaly without muscular or ocular involvement, MONDO:0014077
Inherited white matter disorders v1.168 LAMB1 Sarah Leigh Phenotypes for gene: LAMB1 were changed from Lissencephaly 5, OMIM:615191 to Lissencephaly 5, OMIM:615191; cobblestone lissencephaly without muscular or ocular involvement, MONDO:0014077
Adult onset leukodystrophy v2.36 LAMB1 Sarah Leigh Publications for gene: LAMB1 were set to 32548278
Adult onset leukodystrophy v2.35 PSEN2 Sarah Leigh Tag Q1_23_promote_green tag was added to gene: PSEN2.
Tag Q1_23_NHS_review tag was added to gene: PSEN2.
Adult onset leukodystrophy v2.35 PSEN2 Sarah Leigh reviewed gene: PSEN2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Adult onset leukodystrophy v2.35 PSEN2 Sarah Leigh Classified gene: PSEN2 as Amber List (moderate evidence)
Adult onset leukodystrophy v2.35 PSEN2 Sarah Leigh Gene: psen2 has been classified as Amber List (Moderate Evidence).
Adult onset leukodystrophy v2.34 PSEN2 Sarah Leigh Publications for gene: PSEN2 were set to 9450781
Adult onset leukodystrophy v2.33 PSEN2 Sarah Leigh Mode of inheritance for gene: PSEN2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
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
Adult onset neurodegenerative disorder v3.44 PSEN2 Sarah Leigh Phenotypes for gene: PSEN2 were changed from Alzheimer disease-4, OMIM:606889; Alzheimer disease 4MONDO:0011743 to Alzheimer disease-4, OMIM:606889; Alzheimer disease 4, MONDO:0011743
Adult onset leukodystrophy v2.32 PSEN2 Sarah Leigh Phenotypes for gene: PSEN2 were changed from to Alzheimer disease-4, OMIM:606889; Alzheimer disease 4, MONDO:0011743
Adult onset neurodegenerative disorder v3.43 PSEN2 Sarah Leigh Phenotypes for gene: PSEN2 were changed from Alzheimer disease-4, OMIM:606889 to Alzheimer disease-4, OMIM:606889; Alzheimer disease 4MONDO:0011743
Adult onset leukodystrophy v2.31 PSEN2 Sarah Leigh Publications for gene: PSEN2 were set to
Adult onset leukodystrophy v2.30 PSEN1 Sarah Leigh edited their review of gene: PSEN1: Added comment: PSEN1 variants are sssociated with OMIM:607822 & OMIM:600274, but not with a phenotype in Gen2Phen. Numerous PSEN1 variants have been reported in these conditions and PSEN1 related cerebral amyloid angiopathy is seen within a number of cases of Alzheimer disease, type 3 (OMIM:607822)(PMID: 26888304,11489138, 11395394, 34319632).; Changed rating: GREEN
Adult onset leukodystrophy v2.30 PSEN1 Sarah Leigh Tag Q1_23_promote_green tag was added to gene: PSEN1.
Tag Q1_23_NHS_review tag was added to gene: PSEN1.
Adult onset leukodystrophy v2.30 PSEN1 Sarah Leigh Classified gene: PSEN1 as Amber List (moderate evidence)
Adult onset leukodystrophy v2.30 PSEN1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Adult onset leukodystrophy v2.30 PSEN1 Sarah Leigh Gene: psen1 has been classified as Amber List (Moderate Evidence).
Adult onset leukodystrophy v2.29 PSEN1 Sarah Leigh Mode of inheritance for gene: PSEN1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset leukodystrophy v2.28 PSEN1 Sarah Leigh Phenotypes for gene: PSEN1 were changed from to Alzheimer disease, type 3, OMIM:607822; Alzheimer disease 3, MONDO:0011913; Dementia, frontotemporal, OMIM:600274; semantic dementia, MONDO:0010857
Adult onset leukodystrophy v2.27 PSEN1 Sarah Leigh Publications for gene: PSEN1 were set to
Adult onset leukodystrophy v2.26 PRNP Sarah Leigh edited their review of gene: PRNP: Added comment: Associated with relevant phenotype in OMIM (OMIM:137440), but not associated with a phenotype in Gen2Phen. Numberous PRNP variants have been reported for OMIM:137440.; Changed rating: GREEN
Adult onset leukodystrophy v2.26 PRNP Sarah Leigh Tag Q1_23_promote_green tag was added to gene: PRNP.
Tag Q1_23_NHS_review tag was added to gene: PRNP.
Adult onset leukodystrophy v2.26 PRNP Sarah Leigh Mode of inheritance for gene: PRNP was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset leukodystrophy v2.25 PRNP Sarah Leigh Classified gene: PRNP as Amber List (moderate evidence)
Adult onset leukodystrophy v2.25 PRNP Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Adult onset leukodystrophy v2.25 PRNP Sarah Leigh Gene: prnp has been classified as Amber List (Moderate Evidence).
Adult onset leukodystrophy v2.24 PRNP Sarah Leigh Phenotypes for gene: PRNP were changed from to Cerebral amyloid angiopathy, PRNP-related, OMIM:137440; Gerstmann-Straussler disease, OMIM:137440; Gerstmann-Straussler-Scheinker syndrome, MONDO:0007656
Adult onset leukodystrophy v2.23 GSN Sarah Leigh edited their review of gene: GSN: Added comment: Associated with Amyloidosis, Finnish type, in OMIM and as definitive gene for this phenotype in Gen2Phen. At least 4 variants have been reported (PMID: 25097823; 33973672; 33499149).; Changed rating: GREEN
Adult onset leukodystrophy v2.23 GSN Sarah Leigh Tag Q1_23_promote_green tag was added to gene: GSN.
Tag Q1_23_NHS_review tag was added to gene: GSN.
Adult onset leukodystrophy v2.23 GSN Sarah Leigh Classified gene: GSN as Amber List (moderate evidence)
Adult onset leukodystrophy v2.23 GSN Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Adult onset leukodystrophy v2.23 GSN Sarah Leigh Gene: gsn has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v3.42 GSN Sarah Leigh Publications for gene: GSN were set to 25097823
Adult onset leukodystrophy v2.22 GSN Sarah Leigh Publications for gene: GSN were set to 25097823; 7550233
Adult onset leukodystrophy v2.21 GSN Sarah Leigh Mode of inheritance for gene: GSN was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset leukodystrophy v2.20 GSN Sarah Leigh Publications for gene: GSN were set to 25097823
Adult onset neurodegenerative disorder v3.41 GSN Sarah Leigh Publications for gene: GSN were set to
Adult onset leukodystrophy v2.19 GSN Sarah Leigh Publications for gene: GSN were set to
Adult onset leukodystrophy v2.18 GSN Sarah Leigh Phenotypes for gene: GSN were changed from to Amyloidosis, Finnish type, OMIM:105120; Finnish type amyloidosis, MONDO:0007097
Adult onset neurodegenerative disorder v3.40 GSN Sarah Leigh Phenotypes for gene: GSN were changed from Amyloidosis, Finnish type, OMIM:105120 to Amyloidosis, Finnish type, OMIM:105120; Finnish type amyloidosis, MONDO:0007097
Adult onset leukodystrophy v2.17 ITM2B Sarah Leigh Mode of inheritance for gene: ITM2B was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset leukodystrophy v2.16 ITM2B Sarah Leigh edited their review of gene: ITM2B: Added comment: Associated with relevant phenotypes in OMIM (OMIM:176500 & OMIM:117300), but not associated with these phenotypes in Gen2Phen. Two terminating variants have been reported, one for each of the above phenotypes (PMID: 10391242, 10781099).; Changed rating: GREEN
Adult onset leukodystrophy v2.16 ITM2B Sarah Leigh Tag Q1_23_promote_green tag was added to gene: ITM2B.
Tag Q1_23_NHS_review tag was added to gene: ITM2B.
Adult onset leukodystrophy v2.16 ITM2B Sarah Leigh Classified gene: ITM2B as Amber List (moderate evidence)
Adult onset leukodystrophy v2.16 ITM2B Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Adult onset leukodystrophy v2.16 ITM2B Sarah Leigh Gene: itm2b has been classified as Amber List (Moderate Evidence).
Adult onset leukodystrophy v2.15 ITM2B Sarah Leigh Phenotypes for gene: ITM2B were changed from to Dementia, familial British, OMIM:176500; ABri amyloidosis, MONDO:0008306; Dementia, familial Danish, OMIM:117300; ADan amyloidosis, MONDO:0007297
Adult onset neurodegenerative disorder v3.39 ITM2B Sarah Leigh Phenotypes for gene: ITM2B were changed from Dementia, familial British, OMIM:176500 to Dementia, familial British, OMIM:176500; ABri amyloidosis, MONDO:0008306; Dementia, familial Danish, OMIM:117300; ADan amyloidosis, MONDO:0007297
Adult onset neurodegenerative disorder v3.38 ITM2B Sarah Leigh Publications for gene: ITM2B were set to 29525180; 10391242; 10781099
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.83 ITM2B Sarah Leigh Phenotypes for gene: ITM2B were changed from Dementia, familial British, 176500 to Dementia, familial British, OMIM:176500; ABri amyloidosis, MONDO:0008306; Dementia, familial Danish, OMIM:117300; ADan amyloidosis, MONDO:0007297
Adult onset leukodystrophy v2.14 ITM2B Sarah Leigh Publications for gene: ITM2B were set to
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.82 ITM2B Sarah Leigh Publications for gene: ITM2B were set to 10391242; 10781099
Adult onset neurodegenerative disorder v3.37 ITM2B Sarah Leigh Publications for gene: ITM2B were set to 29525180; 10391242; 210391242; 10781099
Early onset dementia (encompassing fronto-temporal dementia and prion disease) v1.81 ITM2B Sarah Leigh Publications for gene: ITM2B were set to
Adult onset leukodystrophy v2.13 CST3 Sarah Leigh reviewed gene: CST3: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Adult onset leukodystrophy v2.13 CST3 Sarah Leigh Publications for gene: CST3 were set to 2900981; 3495457; 1352269; 3673496; 7482672
Hereditary systemic amyloidosis v1.16 CST3 Sarah Leigh Publications for gene: CST3 were set to 2900981; 3495457; 1352269; 3673496; 7482672
Adult onset neurodegenerative disorder v3.36 TTR Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: TTR.
Adult onset neurodegenerative disorder v3.36 LAMB1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: LAMB1.
Adult onset leukodystrophy v2.12 CST3 Sarah Leigh Tag founder-effect tag was added to gene: CST3.
Adult onset neurodegenerative disorder v3.36 GSN Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: GSN.
Adult onset leukodystrophy v2.12 CST3 Sarah Leigh Classified gene: CST3 as Amber List (moderate evidence)
Adult onset leukodystrophy v2.12 CST3 Sarah Leigh Gene: cst3 has been classified as Amber List (Moderate Evidence).
Adult onset leukodystrophy v2.11 CST3 Sarah Leigh Publications for gene: CST3 were set to
Adult onset neurodegenerative disorder v3.36 CST3 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: CST3.
Hereditary systemic amyloidosis v1.15 CST3 Sarah Leigh Publications for gene: CST3 were set to 2900981; 3495457; 1352269; 367349; 7482672
Adult onset leukodystrophy v2.10 CST3 Sarah Leigh Mode of inheritance for gene: CST3 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset leukodystrophy v2.9 CST3 Sarah Leigh Phenotypes for gene: CST3 were changed from Cerebral amyloid angiopathy, OMIM:105150; ACys amyloidosis, MONDO:0007098 to Cerebral amyloid angiopathy, OMIM:105150; ACys amyloidosis, MONDO:0007098
Adult onset leukodystrophy v2.9 CST3 Sarah Leigh Phenotypes for gene: CST3 were changed from Cerebral amyloid angiopathy, OMIM:105150 to Cerebral amyloid angiopathy, OMIM:105150; ACys amyloidosis, MONDO:0007098
Adult onset neurodegenerative disorder v3.36 TREX1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: TREX1.
Adult onset neurodegenerative disorder v3.36 GLA Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: GLA.
Adult onset neurodegenerative disorder v3.36 COL4A2 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: COL4A2.
Adult onset neurodegenerative disorder v3.36 COL4A1 Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: COL4A1.
Adult onset neurodegenerative disorder v3.36 CTSA Achchuthan Shanmugasundram Tag Q1_23_promote_green tag was added to gene: CTSA.
Adult onset neurodegenerative disorder v3.36 CTSA Achchuthan Shanmugasundram changed review comment from: Comment on classification: This gene should be promoted to GREEN at the next GMS panel update as this gene has been implicated in >10 unrelated patients of multiple ancestry including Europeans and Chinese. The evidence from literature also confirms the adult-onset nature of this disorder.

This gene has not yet been associated with this disorder caused by autosomal dominant inheritance in OMIM. However, it has already been associated with galactosialidosis (autosomal recessive disorder) ion both OMIM and G2P.; to: Comment on classification: This gene should be promoted to GREEN at the next GMS panel update as this gene has been implicated in >10 unrelated patients of multiple ancestry including Europeans and Chinese. The evidence from literature also confirms the adult-onset nature of this disorder.

This gene has not yet been associated with this disorder caused by autosomal dominant inheritance in OMIM. However, it has already been associated with galactosialidosis (autosomal recessive disorder) in both OMIM and G2P.
Adult onset leukodystrophy v2.8 APP Arina Puzriakova Tag Q1_23_promote_green tag was added to gene: APP.
Adult onset neurodegenerative disorder v3.36 CTSA Achchuthan Shanmugasundram changed review comment from: Comment on classification: This gene should be promoted to GREEN at the next GMS panel update as this gene has been implicated in >10 unrelated patients of multiple ancestry including Europeans and Chinese. The evidence from literature also confirms the adult-onset nature of this disorder.

This gene has not yet been associated with this disorder caused by autosomal dominant inheritance in OMIM. However, it has already been associated with galactosialidosis (autosomal recessive disorder) ion both OMIM and G2P; to: Comment on classification: This gene should be promoted to GREEN at the next GMS panel update as this gene has been implicated in >10 unrelated patients of multiple ancestry including Europeans and Chinese. The evidence from literature also confirms the adult-onset nature of this disorder.

This gene has not yet been associated with this disorder caused by autosomal dominant inheritance in OMIM. However, it has already been associated with galactosialidosis (autosomal recessive disorder) ion both OMIM and G2P.
Adult onset neurodegenerative disorder v3.36 CTSA Achchuthan Shanmugasundram changed review comment from: Comment on classification: This gene should be promoted to GREEN for adult-onset neurodegenerative disorders as this gene has been implicated in >10 unrelated patients of multiple ancestry including Europeans and Chinese. The evidence from literature also confirms the adult-onset nature of this disorder.

This gene has not yet been associated with this disorder caused by autosomal dominant inheritance in OMIM. However, it has already been associated with galactosialidosis (autosomal recessive disorder) ion both OMIM and G2P; to: Comment on classification: This gene should be promoted to GREEN at the next GMS panel update as this gene has been implicated in >10 unrelated patients of multiple ancestry including Europeans and Chinese. The evidence from literature also confirms the adult-onset nature of this disorder.

This gene has not yet been associated with this disorder caused by autosomal dominant inheritance in OMIM. However, it has already been associated with galactosialidosis (autosomal recessive disorder) ion both OMIM and G2P
Adult onset neurodegenerative disorder v3.36 TTR Achchuthan Shanmugasundram Publications for gene: TTR were set to
Adult onset neurodegenerative disorder v3.35 TTR Achchuthan Shanmugasundram Phenotypes for gene: TTR were changed from to Amyloidosis, hereditary, transthyretin-related, OMIM:105210; Carpal tunnel syndrome, familial, OMIM:115430
Adult onset neurodegenerative disorder v3.34 TTR Achchuthan Shanmugasundram Mode of inheritance for gene: TTR was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset neurodegenerative disorder v3.33 TTR Achchuthan Shanmugasundram Classified gene: TTR as Amber List (moderate evidence)
Adult onset neurodegenerative disorder v3.33 TTR Achchuthan Shanmugasundram Gene: ttr has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v3.32 TTR Achchuthan Shanmugasundram edited their review of gene: TTR: Added comment: Comment on classification: Sufficient evidence to promote this gene to Green at the next GMS panel update. >3 unrelated cases including relevant phenotypes and with adult-onset reported in patients.

This gene has been associated with relevant phenotypes in OMIM, but not in G2P.; Changed phenotypes to: Amyloidosis, hereditary, transthyretin-related, OMIM:105210, Carpal tunnel syndrome, familial, OMIM:115430
Adult onset neurodegenerative disorder v3.32 TTR Achchuthan Shanmugasundram reviewed gene: TTR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Amyloidosis, hereditary, transthyretin-related, OMIM: 105210; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset neurodegenerative disorder v3.32 LAMB1 Achchuthan Shanmugasundram Phenotypes for gene: LAMB1 were changed from to Lissencephaly 5, OMIM:615191
Adult onset neurodegenerative disorder v3.31 LAMB1 Achchuthan Shanmugasundram Mode of inheritance for gene: LAMB1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v3.30 LAMB1 Achchuthan Shanmugasundram Mode of inheritance for gene: LAMB1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v3.29 LAMB1 Achchuthan Shanmugasundram Classified gene: LAMB1 as Amber List (moderate evidence)
Adult onset neurodegenerative disorder v3.29 LAMB1 Achchuthan Shanmugasundram Gene: lamb1 has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v3.28 LAMB1 Achchuthan Shanmugasundram reviewed gene: LAMB1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lissencephaly 5, OMIM:615191; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v3.28 GSN Achchuthan Shanmugasundram Phenotypes for gene: GSN were changed from to Amyloidosis, Finnish type, OMIM:105120
Adult onset neurodegenerative disorder v3.27 GSN Achchuthan Shanmugasundram Mode of inheritance for gene: GSN was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset neurodegenerative disorder v3.26 GSN Achchuthan Shanmugasundram Classified gene: GSN as Amber List (moderate evidence)
Adult onset neurodegenerative disorder v3.26 GSN Achchuthan Shanmugasundram Gene: gsn has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v3.25 GSN Achchuthan Shanmugasundram reviewed gene: GSN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Amyloidosis, Finnish type, OMIM:105120; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset neurodegenerative disorder v3.25 CST3 Achchuthan Shanmugasundram Mode of inheritance for gene: CST3 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset neurodegenerative disorder v3.24 CST3 Achchuthan Shanmugasundram Classified gene: CST3 as Amber List (moderate evidence)
Adult onset neurodegenerative disorder v3.24 CST3 Achchuthan Shanmugasundram Gene: cst3 has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v3.23 CST3 Achchuthan Shanmugasundram Classified gene: CST3 as Amber List (moderate evidence)
Adult onset neurodegenerative disorder v3.23 CST3 Achchuthan Shanmugasundram Gene: cst3 has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v3.22 CST3 Achchuthan Shanmugasundram reviewed gene: CST3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebral amyloid angiopathy, OMIM:105150; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset neurodegenerative disorder v3.22 TREX1 Achchuthan Shanmugasundram Phenotypes for gene: TREX1 were changed from Dystonia to Aicardi-Goutieres syndrome 1, dominant and recessive, OMIM:225750; Vasculopathy, retinal, with cerebral leukoencephalopathy and systemic manifestations, OMIM:192315
Adult onset neurodegenerative disorder v3.21 TREX1 Achchuthan Shanmugasundram Mode of inheritance for gene: TREX1 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v3.20 TREX1 Achchuthan Shanmugasundram Classified gene: TREX1 as Amber List (moderate evidence)
Adult onset neurodegenerative disorder v3.20 TREX1 Achchuthan Shanmugasundram Gene: trex1 has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v3.19 TREX1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: Sufficient evidence to promote this gene to Green at the next GMS panel update. >3 unrelated cases including relevant phenotypes and with confirmed cases of adult-onset.

TREX1 has also been associated with relevant phenotypes in both OMIM and G2P.; to: Comment on classification: Sufficient evidence to promote this gene to Green at the next GMS panel update. >3 unrelated cases including relevant phenotypes and with confirmed cases of adult-onset.

TREX1 has also been associated with relevant phenotypes in both OMIM and G2P.
Adult onset neurodegenerative disorder v3.19 TREX1 Achchuthan Shanmugasundram Deleted their comment
Adult onset neurodegenerative disorder v3.19 TREX1 Achchuthan Shanmugasundram commented on gene: TREX1: Comment on list classification: Sufficient evidence to promote this gene to Green at the next GMS panel update. >3 unrelated cases including relevant phenotypes and with confirmed cases of adult-onset.

TREX1 has also been associated with relevant phenotypes in both OMIM and G2P.
Adult onset neurodegenerative disorder v3.19 TREX1 Achchuthan Shanmugasundram reviewed gene: TREX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Aicardi-Goutieres syndrome 1, dominant and recessive, OMIM:225750, Vasculopathy, retinal, with cerebral leukoencephalopathy and systemic manifestations, OMIM:192315; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v3.19 GLA Achchuthan Shanmugasundram Phenotypes for gene: GLA were changed from to Fabry disease, OMIM:301500
Adult onset neurodegenerative disorder v3.18 GLA Achchuthan Shanmugasundram Mode of inheritance for gene: GLA was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Adult onset neurodegenerative disorder v3.17 GLA Achchuthan Shanmugasundram Classified gene: GLA as Amber List (moderate evidence)
Adult onset neurodegenerative disorder v3.17 GLA Achchuthan Shanmugasundram Gene: gla has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v3.16 GLA Achchuthan Shanmugasundram reviewed gene: GLA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Fabry disease, OMIM:301500; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Adult onset neurodegenerative disorder v3.16 COL4A2 Achchuthan Shanmugasundram Phenotypes for gene: COL4A2 were changed from to Brain small vessel disease 2, OMIM:614483; {Hemorrhage, intracerebral, susceptibility to}, OMIM:614519
Adult onset neurodegenerative disorder v3.15 COL4A2 Achchuthan Shanmugasundram Mode of inheritance for gene: COL4A2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset neurodegenerative disorder v3.14 COL4A2 Achchuthan Shanmugasundram Classified gene: COL4A2 as Amber List (moderate evidence)
Adult onset neurodegenerative disorder v3.14 COL4A2 Achchuthan Shanmugasundram Gene: col4a2 has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v3.13 COL4A2 Achchuthan Shanmugasundram reviewed gene: COL4A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Brain small vessel disease 2, OMIM:614483, {Hemorrhage, intracerebral, susceptibility to}, OMIM:614519; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset neurodegenerative disorder v3.13 COL4A1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: Sufficient evidence to promote this gene to Green at the next GMS panel update. >3 unrelated cases including relevant phenotypes and most patients had adult-onset of disorder.; to: Comment on list classification: Sufficient evidence to promote this gene to Green at the next GMS panel update. >3 unrelated cases including relevant phenotypes and most patients had adult-onset of disorder.

Relevant phenotypes have already been reported in both OMIM and G2P.
Adult onset neurodegenerative disorder v3.13 COL4A1 Achchuthan Shanmugasundram Phenotypes for gene: COL4A1 were changed from to Brain small vessel disease with or without ocular anomalies, OMIM:175780; Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, OMIM:611773; Microangiopathy and leukoencephalopathy, pontine, autosomal dominant, OMIM:618564; {Hemorrhage, intracerebral, susceptibility to}, OMIM:614519
Adult onset neurodegenerative disorder v3.12 COL4A1 Achchuthan Shanmugasundram Mode of inheritance for gene: COL4A1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset neurodegenerative disorder v3.11 COL4A1 Achchuthan Shanmugasundram Classified gene: COL4A1 as Amber List (moderate evidence)
Adult onset neurodegenerative disorder v3.11 COL4A1 Achchuthan Shanmugasundram Gene: col4a1 has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v3.10 COL4A1 Achchuthan Shanmugasundram reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Brain small vessel disease with or without ocular anomalies, OMIM:175780, Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, OMIM:611773, Microangiopathy and leukoencephalopathy, pontine, autosomal dominant, OMIM:618564, {Hemorrhage, intracerebral, susceptibility to}, OMIM:614519; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset neurodegenerative disorder v3.10 COL4A1 Achchuthan Shanmugasundram Deleted their review
Adult onset neurodegenerative disorder v3.10 COL4A1 Achchuthan Shanmugasundram reviewed gene: COL4A1: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Brain small vessel disease with or without ocular anomalies, OMIM:175780, Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps, OMIM:v; Mode of inheritance: None
IUGR and IGF abnormalities v1.56 IGFALS Arina Puzriakova Phenotypes for gene: IGFALS were changed from Short stature; delayed puberty; very low IGF-I levels to Acid-labile subunit, deficiency of, OMIM:615961; Short stature; Delayed puberty; Very low IGF-I levels
COVID-19 research v1.135 STAT5B Arina Puzriakova Phenotypes for gene: STAT5B were changed from Combined immunodeficiency; T-B+ SCID; Growth-hormone insensitive dwarfism, dysmorphic features, eczema, lymphocytic interstitial pneumonitis, autoimmunity; Growth hormone insensitivity with immunodeficiency 245590; Combined immunodeficiencies with associated or syndromic features to Growth hormone insensitivity with immune dysregulation 1, autosomal recessive, OMIM:245590; Growth hormone insensitivity with immune dysregulation 2, autosomal dominant, OMIM:618985; T-B+ SCID; Combined immunodeficiency; Growth-hormone insensitive dwarfism, dysmorphic features, eczema, lymphocytic interstitial pneumonitis, autoimmunity; Combined immunodeficiencies with associated or syndromic features
Intellectual disability v4.31 STAT5B Arina Puzriakova Mode of inheritance for gene: STAT5B was changed from to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v3.2 STAT5B Arina Puzriakova Phenotypes for gene: STAT5B were changed from Growth hormone insensitivity with immunodeficiency 245590; T-B+ SCID; Combined immunodeficiency; Growth-hormone insensitive dwarfism, dysmorphic features, eczema, lymphocytic interstitial pneumonitis, autoimmunity; Combined immunodeficiencies with associated or syndromic features to Growth hormone insensitivity with immune dysregulation 1, autosomal recessive, OMIM:245590; Growth hormone insensitivity with immune dysregulation 2, autosomal dominant, OMIM:618985; T-B+ SCID; Combined immunodeficiency; Growth-hormone insensitive dwarfism, dysmorphic features, eczema, lymphocytic interstitial pneumonitis, autoimmunity; Combined immunodeficiencies with associated or syndromic features
Intellectual disability v4.30 STAT5B Arina Puzriakova Phenotypes for gene: STAT5B were changed from to Growth hormone insensitivity with immune dysregulation 1, autosomal recessive, OMIM:245590; Growth hormone insensitivity with immune dysregulation 2, autosomal dominant, OMIM:618985
Intellectual disability v4.29 GHR Arina Puzriakova Phenotypes for gene: GHR were changed from Laron dwarfism, 262500; Short stature, 604271; {Hypercholesterolemia, familial, modifier of}, 143890; Increased responsiveness to growth hormone to Laron dwarfism, OMIM:262500; Growth hormone insensitivity, partial, OMIM:604271; Increased responsiveness to growth hormone, OMIM:604271
Skeletal dysplasia v3.3 GHR Arina Puzriakova Phenotypes for gene: GHR were changed from {Hypercholesterolemia, familial, modification of}, 143890; Growth hormone insensitivity; Short stature, 604271; increased responsiveness to growth hormone 604271; Increased responsiveness to growth hormone; Laron dwarfism, 262500; Proportionate Short Stature/Small for Gestational Age to Laron dwarfism, OMIM:262500; Growth hormone insensitivity, partial, OMIM:604271; Increased responsiveness to growth hormone, OMIM:604271
Pituitary hormone deficiency v2.104 GHR Arina Puzriakova changed review comment from: Review submitted on behalf of Helen Storr - "This gene is currently on panel R159.1 Pituitary hormone deficiency. It should be removed from this panel as it does not cause GH deficiency - it is causes defective GH signalling."

Variants in this gene confer dysfunction of the growth hormone receptor resulting in altered signalling. GH levels are typically normal or increased and therefore inclusion of GHR on this panel should be re-evaluated by the GMS Endocrinology Specialist Test Group.

This gene may possibly be more appropriate for R147 Growth failure in early childhood, but this is currently also pending expert review (https://panelapp.genomicsengland.co.uk/panels/473/gene/GHR/); to: Review submitted on behalf of Helen Storr - "This gene is currently on panel R159.1 Pituitary hormone deficiency. It should be removed from this panel as it does not cause GH deficiency - it is causes defective GH signalling."

Variants in this gene confer dysfunction of the growth hormone receptor resulting in altered signalling. GH levels are typically normal or increased and therefore inclusion of GHR on this panel should be re-evaluated by the GMS Endocrinology Specialist Test Group.

GHR may possibly be more appropriate for R147 Growth failure in early childhood, but relevance is currently also pending expert review (https://panelapp.genomicsengland.co.uk/panels/473/gene/GHR/)
Pituitary hormone deficiency v2.104 GHR Arina Puzriakova changed review comment from: Review submitted on behalf of Helen Storr - "This gene is currently on panel R159.1 Pituitary hormone deficiency. It should be removed from this panel as it does not cause GH deficiency - it is causes defective GH signalling."

Variants in this gene confer dysfunction of the growth hormone receptor resulting in altered signalling. GH levels are typically normal or increased and therefore inclusion of GHR on this panel should be re-evaluated by the GMS Endocrinology Specialist Test Group.; to: Review submitted on behalf of Helen Storr - "This gene is currently on panel R159.1 Pituitary hormone deficiency. It should be removed from this panel as it does not cause GH deficiency - it is causes defective GH signalling."

Variants in this gene confer dysfunction of the growth hormone receptor resulting in altered signalling. GH levels are typically normal or increased and therefore inclusion of GHR on this panel should be re-evaluated by the GMS Endocrinology Specialist Test Group.

This gene may possibly be more appropriate for R147 Growth failure in early childhood, but this is currently also pending expert review (https://panelapp.genomicsengland.co.uk/panels/473/gene/GHR/)
Pituitary hormone deficiency v2.104 GHR Arina Puzriakova Tag Q1_23_demote_red tag was added to gene: GHR.
Tag Q1_23_expert_review tag was added to gene: GHR.
Pituitary hormone deficiency v2.104 GHR Arina Puzriakova commented on gene: GHR
Pituitary hormone deficiency v2.104 GHR Arina Puzriakova Phenotypes for gene: GHR were changed from Laron dwarfism (262500); Increased responsiveness to growth hormone (604271); Growth hormone insensitivity, partial (604271) to Laron dwarfism, OMIM:262500; Growth hormone insensitivity, partial, OMIM:604271; Increased responsiveness to growth hormone, OMIM:604271
Paediatric pseudo-obstruction syndrome v0.213 PHOX2B Arina Puzriakova Tag STR tag was added to gene: PHOX2B.
Paediatric pseudo-obstruction syndrome v0.213 TPM3 Arina Puzriakova Phenotypes for gene: TPM3 were changed from to Megacolon
Paediatric pseudo-obstruction syndrome v0.212 TPM3 Arina Puzriakova Mode of inheritance for gene: TPM3 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.211 SURF1 Arina Puzriakova Mode of inheritance for gene: SURF1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.210 SDHA Arina Puzriakova Phenotypes for gene: SDHA were changed from to Mitochondrial complex II deficiency, nuclear type 1, OMIM:252011
Paediatric pseudo-obstruction syndrome v0.209 SDHA Arina Puzriakova Mode of inheritance for gene: SDHA was changed from to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.208 SCN10A Arina Puzriakova Phenotypes for gene: SCN10A were changed from to Colon sensory neurons activation
Paediatric pseudo-obstruction syndrome v0.207 SCN10A Arina Puzriakova Mode of inheritance for gene: SCN10A was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.206 NRTN Arina Puzriakova Publications for gene: NRTN were set to
Paediatric pseudo-obstruction syndrome v0.205 NRTN Arina Puzriakova Phenotypes for gene: NRTN were changed from to susceptibility to Hirschsprung disease
Paediatric pseudo-obstruction syndrome v0.204 NRTN Arina Puzriakova Mode of inheritance for gene: NRTN was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.203 NKX2-1 Arina Puzriakova Publications for gene: NKX2-1 were set to
Paediatric pseudo-obstruction syndrome v0.202 NKX2-1 Arina Puzriakova Phenotypes for gene: NKX2-1 were changed from to Megacolon, oesophageal atresia
Paediatric pseudo-obstruction syndrome v0.201 NKX2-1 Arina Puzriakova Mode of inheritance for gene: NKX2-1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.200 NDUFS1 Arina Puzriakova Phenotypes for gene: NDUFS1 were changed from to Mitochondrial complex I deficiency, nuclear type 5, OMIM:618226
Paediatric pseudo-obstruction syndrome v0.199 NDUFS1 Arina Puzriakova Mode of inheritance for gene: NDUFS1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.198 KIF26A Arina Puzriakova Phenotypes for gene: KIF26A were changed from to GDNF-Ret in ENS development
Paediatric pseudo-obstruction syndrome v0.197 KIF26A Arina Puzriakova Mode of inheritance for gene: KIF26A was changed from to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.196 FOCAD Arina Puzriakova Mode of inheritance for gene: FOCAD was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.195 MPV17 Arina Puzriakova Mode of inheritance for gene: MPV17 was changed from to BIALLELIC, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v3.10 CTSA Achchuthan Shanmugasundram changed review comment from: Comment on classification: This gene should be promoted to GREEN for adult-onset neurodegenerative disorders as this gene has been implicated in >10 unrelated patients of multiple ancestry including Europeans and Chinese.

This gene has not yet been associated with this disorder caused by autosomal dominant inheritance in OMIM. However, it has already been associated with galactosialidosis (autosomal recessive disorder) ion both OMIM and G2P; to: Comment on classification: This gene should be promoted to GREEN for adult-onset neurodegenerative disorders as this gene has been implicated in >10 unrelated patients of multiple ancestry including Europeans and Chinese. The evidence from literature also confirms the adult-onset nature of this disorder.

This gene has not yet been associated with this disorder caused by autosomal dominant inheritance in OMIM. However, it has already been associated with galactosialidosis (autosomal recessive disorder) ion both OMIM and G2P
Adult onset neurodegenerative disorder v3.10 CTSA Achchuthan Shanmugasundram Phenotypes for gene: CTSA were changed from Cathepsin a-related arteriopathy-strokes-leukoencephalopathy, MONDO:0035551 to Cathepsin A-related arteriopathy-strokes-leukoencephalopathy, MONDO:0035551
Adult onset neurodegenerative disorder v3.9 CTSA Achchuthan Shanmugasundram Phenotypes for gene: CTSA were changed from to Cathepsin a-related arteriopathy-strokes-leukoencephalopathy, MONDO:0035551
Adult onset neurodegenerative disorder v3.8 CTSA Achchuthan Shanmugasundram Publications for gene: CTSA were set to
Adult onset neurodegenerative disorder v3.7 CTSA Achchuthan Shanmugasundram Mode of inheritance for gene: CTSA was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset neurodegenerative disorder v3.6 CTSA Achchuthan Shanmugasundram Classified gene: CTSA as Amber List (moderate evidence)
Adult onset neurodegenerative disorder v3.6 CTSA Achchuthan Shanmugasundram Gene: ctsa has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v3.5 CTSA Achchuthan Shanmugasundram changed review comment from: Comment on classification: This gene should be rated GREEN for adult-onset neurodegenerative disorders as this gene has been implicated in >10 unrelated patients of multiple ancestry including Europeans and Chinese.

This gene has not yet been associated with this disorder caused by autosomal dominant inheritance in OMIM. However, it has already been associated with galactosialidosis (autosomal recessive disorder) ion both OMIM and G2P; to: Comment on classification: This gene should be promoted to GREEN for adult-onset neurodegenerative disorders as this gene has been implicated in >10 unrelated patients of multiple ancestry including Europeans and Chinese.

This gene has not yet been associated with this disorder caused by autosomal dominant inheritance in OMIM. However, it has already been associated with galactosialidosis (autosomal recessive disorder) ion both OMIM and G2P
Adult onset neurodegenerative disorder v3.5 CTSA Achchuthan Shanmugasundram reviewed gene: CTSA: Rating: GREEN; Mode of pathogenicity: None; Publications: 27664989, 28702507, 35904593; Phenotypes: cathepsin a-related arteriopathy-strokes-leukoencephalopathy, MONDO:0035551; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Familial cerebral small vessel disease v1.16 CST3 Arina Puzriakova Phenotypes for gene: CST3 were changed from Stroke; haemorrhagic stroke; dementia; Cerebral amyloid angiopathy 105150 to Cerebral amyloid angiopathy, OMIM:105150
Periodic fever syndromes v1.33 CST3 Arina Puzriakova Phenotypes for gene: CST3 were changed from Cerebral amyloid angiopathy 105150 to Cerebral amyloid angiopathy, OMIM:105150
Adult onset neurodegenerative disorder v3.5 CST3 Arina Puzriakova Phenotypes for gene: CST3 were changed from to Cerebral amyloid angiopathy, OMIM:105150
Adult onset leukodystrophy v2.8 CST3 Arina Puzriakova Phenotypes for gene: CST3 were changed from to Cerebral amyloid angiopathy, OMIM:105150
Adult onset leukodystrophy v2.7 APP Arina Puzriakova Classified gene: APP as Amber List (moderate evidence)
Adult onset leukodystrophy v2.7 APP Arina Puzriakova Added comment: Comment on list classification: Sufficient evidence to promote this gene to Green at the next GMS panel update. >3 unrelated cases including relevant phenotype (leukoencephalopathy) and age of onset (~44 to 60 years).
Adult onset leukodystrophy v2.7 APP Arina Puzriakova Gene: app has been classified as Amber List (Moderate Evidence).
Adult onset leukodystrophy v2.6 APP Arina Puzriakova Publications for gene: APP were set to
Familial cerebral small vessel disease v1.15 APP Arina Puzriakova Phenotypes for gene: APP were changed from Haemorrhagic stroke; stroke; ischaemic stroke; leukoencephalopathy; seizures; Cerebral amyloid angiopathy, Dutch, Italian, Iowa, Flemish, Arctic variants 605714 to Cerebral amyloid angiopathy, Dutch, Italian, Iowa, Flemish, Arctic variants, OMIM:605714; Haemorrhagic stroke; Ischaemic stroke; Leukoencephalopathy; Seizures
Periodic fever syndromes v1.32 APP Arina Puzriakova Phenotypes for gene: APP were changed from Cerebral amyloid angiopathy, Dutch, Italian, Iowa, Flemish, Arctic variants 605714 to Cerebral amyloid angiopathy, Dutch, Italian, Iowa, Flemish, Arctic variants, OMIM:605714
Adult onset leukodystrophy v2.5 APP Arina Puzriakova Mode of inheritance for gene: APP was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset leukodystrophy v2.4 APP Arina Puzriakova Phenotypes for gene: APP were changed from to Cerebral amyloid angiopathy, Dutch, Italian, Iowa, Flemish, Arctic variants, OMIM:605714
Familial Hirschsprung Disease v1.10 EDNRB Arina Puzriakova Phenotypes for gene: EDNRB were changed from susceptibility to Hirschsprung disease 2, 600155; Waardenburg syndrome, type 4A, 277580; {Hirschsprung disease, susceptibility to, 2}, 600155; Waardenburg syndrome, type 4A, 277580; Hirschsprung Disease, Recessive; Waardenburg; HSCR (short-segment type); colonic aganglionosis; Shah-Waardenburg syndrome; long-segment Hirschsprung's disease; short-segment Hirschsprung's disease to Waardenburg syndrome, type 4A, OMIM:277580; {Hirschsprung disease, susceptibility to, 2}, OMIM:600155; ?ABCD syndrome, OMIM:600501; Colonic aganglionosis; Shah-Waardenburg syndrome; Long-segment Hirschsprung's disease; Short-segment Hirschsprung's disease
Paediatric pseudo-obstruction syndrome v0.194 EDNRB Arina Puzriakova Publications for gene: EDNRB were set to
Paediatric pseudo-obstruction syndrome v0.193 EDNRB Arina Puzriakova Classified gene: EDNRB as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.193 EDNRB Arina Puzriakova Added comment: Comment on list classification: Sufficient evidence to rate this gene as Green. Mouse model of colonic aganglionosis plus >3 unrelated cases supporting gene:disease association (e.g. PMID:20009762, 10528251, 25852447, 16618617).
Paediatric pseudo-obstruction syndrome v0.193 EDNRB Arina Puzriakova Gene: ednrb has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.192 EDNRB Arina Puzriakova Tag monogenic-polygenic tag was added to gene: EDNRB.
Paediatric pseudo-obstruction syndrome v0.192 EDNRB Arina Puzriakova commented on gene: EDNRB
Paediatric pseudo-obstruction syndrome v0.192 EDNRB Arina Puzriakova Mode of inheritance for gene: EDNRB was changed from to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.191 EDNRB Arina Puzriakova Phenotypes for gene: EDNRB were changed from to Waardenburg syndrome, type 4A, OMIM:277580; {Hirschsprung disease, susceptibility to, 2}, OMIM:600155; ?ABCD syndrome, OMIM:600501
Paediatric pseudo-obstruction syndrome v0.190 EDN3 Arina Puzriakova Classified gene: EDN3 as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.190 EDN3 Arina Puzriakova Added comment: Comment on list classification: Sufficient evidence to rate this gene as Green. >3 unrelated cases of EDN3 variants causing Waardenburg syndrome, type 4 (WS4). Note that WS4 is diagnosed when WS2 is accompanied by Hirschsprung disease. Hirschsprung's disease also occurs in ~16% of patients with congenital central hypoventilation syndrome/CCHS, which is also caused by EDN3 variants.
Paediatric pseudo-obstruction syndrome v0.190 EDN3 Arina Puzriakova Gene: edn3 has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.189 EDN3 Arina Puzriakova commented on gene: EDN3
Paediatric pseudo-obstruction syndrome v0.189 EDN3 Arina Puzriakova Tag monogenic-polygenic tag was added to gene: EDN3.
Paediatric pseudo-obstruction syndrome v0.189 EDN3 Arina Puzriakova Mode of inheritance for gene: EDN3 was changed from to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.188 EDN3 Arina Puzriakova Publications for gene: EDN3 were set to
Paediatric pseudo-obstruction syndrome v0.187 EDN3 Arina Puzriakova Phenotypes for gene: EDN3 were changed from to Waardenburg syndrome, type 4B, OMIM:613265; {Hirschsprung disease, susceptibility to, 4}, OMIM:613712
Paediatric pseudo-obstruction syndrome v0.186 ECE1 Arina Puzriakova Publications for gene: ECE1 were set to
Paediatric pseudo-obstruction syndrome v0.185 ECE1 Arina Puzriakova Classified gene: ECE1 as Amber List (moderate evidence)
Paediatric pseudo-obstruction syndrome v0.185 ECE1 Arina Puzriakova Added comment: Comment on list classification: Only a single human patient discovered to date - Hofstra et al. (1999, PMID:9915973) identified heterozygosity an R742C mutation in the ECE1 gene in a patient with skip-lesions Hirschsprung disease, cardiac defects, craniofacial abnormalities and other dysmorphic features, and autonomic dysfunction (HCAD, MIM:613870). Given mouse model displays distal intestinal aganglionosis (PMID: 9449665; 17131407) have rated Amber but additional human cases are required to meet diagnostic-grade criteria.
Paediatric pseudo-obstruction syndrome v0.185 ECE1 Arina Puzriakova Gene: ece1 has been classified as Amber List (Moderate Evidence).
Paediatric pseudo-obstruction syndrome v0.184 ECE1 Arina Puzriakova Mode of inheritance for gene: ECE1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.183 ECE1 Arina Puzriakova Phenotypes for gene: ECE1 were changed from to ?Hirschsprung disease, cardiac defects, and autonomic dysfunction, OMIM:613870
Paediatric pseudo-obstruction syndrome v0.182 DLX2 Arina Puzriakova Phenotypes for gene: DLX2 were changed from to Abnormal bowel motility in mice
Paediatric pseudo-obstruction syndrome v0.181 DLX2 Arina Puzriakova Publications for gene: DLX2 were set to
Paediatric pseudo-obstruction syndrome v0.180 DLX2 Arina Puzriakova Mode of inheritance for gene: DLX2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.179 DLX2 Arina Puzriakova Classified gene: DLX2 as Red List (low evidence)
Paediatric pseudo-obstruction syndrome v0.179 DLX2 Arina Puzriakova Added comment: Comment on list classification: No human cases with pathogenic DLX2 variants reported to date and therefore this gene should be rated Red.

Mice lacking DLX1 and DLX2 had slower small bowel transit and reduced or absent neurally-mediated contraction complexes, and have reduced vasoactive intestinal peptide (VIP) expression and fewer VIP-lineage neurons in their enteric nervous system. Small bowel motility seemed normal in adult mice lacking only DLX1 (PMID: 32017713).
Paediatric pseudo-obstruction syndrome v0.179 DLX2 Arina Puzriakova Gene: dlx2 has been classified as Red List (Low Evidence).
Paediatric pseudo-obstruction syndrome v0.178 DLX1 Arina Puzriakova changed review comment from: Comment on list classification: No human cases with pathogenic DLX1 variants reported to date and therefore this gene should be rated Red.

Mice lacking DLX1 and DLX2 had slower small bowel transit and reduced or absent neurally-mediated contraction complexes, and have reduced vasoactive intestinal peptide (VIP) expression and fewer VIP-lineage neurons in their enteric nervous system. Small bowel motility seemed normal in adult mice lacking only DLX1.; to: Comment on list classification: No human cases with pathogenic DLX1 variants reported to date and therefore this gene should be rated Red.

Mice lacking DLX1 and DLX2 had slower small bowel transit and reduced or absent neurally-mediated contraction complexes, and have reduced vasoactive intestinal peptide (VIP) expression and fewer VIP-lineage neurons in their enteric nervous system. Small bowel motility seemed normal in adult mice lacking only DLX1 (PMID: 32017713).
Paediatric pseudo-obstruction syndrome v0.178 DLX1 Arina Puzriakova Classified gene: DLX1 as Red List (low evidence)
Paediatric pseudo-obstruction syndrome v0.178 DLX1 Arina Puzriakova Added comment: Comment on list classification: No human cases with pathogenic DLX1 variants reported to date and therefore this gene should be rated Red.

Mice lacking DLX1 and DLX2 had slower small bowel transit and reduced or absent neurally-mediated contraction complexes, and have reduced vasoactive intestinal peptide (VIP) expression and fewer VIP-lineage neurons in their enteric nervous system. Small bowel motility seemed normal in adult mice lacking only DLX1.
Paediatric pseudo-obstruction syndrome v0.178 DLX1 Arina Puzriakova Gene: dlx1 has been classified as Red List (Low Evidence).
Paediatric pseudo-obstruction syndrome v0.177 DLX1 Arina Puzriakova Mode of inheritance for gene: DLX1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.176 DLX1 Arina Puzriakova Publications for gene: DLX1 were set to
Paediatric pseudo-obstruction syndrome v0.175 DLX1 Arina Puzriakova Phenotypes for gene: DLX1 were changed from to Abnormal bowel motility in mice
Paediatric pseudo-obstruction syndrome v0.174 DGUOK Arina Puzriakova Classified gene: DGUOK as Red List (low evidence)
Paediatric pseudo-obstruction syndrome v0.174 DGUOK Arina Puzriakova Added comment: Comment on list classification: Could not find clear evidence linking this gene with intestinal pseudo-obstruction and therefore recommending Red gene rating at this time. DGUOK causes a hepatocerebral mitochondrial depletion disorder characterised by hepatic dysfunction, psychomotor delay, hypotonia, nystagmus/opsoclonus, lactic acidosis, hypoglycemia.
Paediatric pseudo-obstruction syndrome v0.174 DGUOK Arina Puzriakova Gene: dguok has been classified as Red List (Low Evidence).
Paediatric pseudo-obstruction syndrome v0.173 DGUOK Arina Puzriakova Publications for gene: DGUOK were set to
Paediatric pseudo-obstruction syndrome v0.172 DGUOK Arina Puzriakova Phenotypes for gene: DGUOK were changed from to Mitochondrial DNA depletion syndrome 3 (hepatocerebral type), OMIM:251880
Paediatric pseudo-obstruction syndrome v0.171 ZEB2 Achchuthan Shanmugasundram Phenotypes for gene: ZEB2 were changed from to Mowat-Wilson syndrome, OMIM:235730
Paediatric pseudo-obstruction syndrome v0.170 ZEB2 Achchuthan Shanmugasundram Publications for gene: ZEB2 were set to
Paediatric pseudo-obstruction syndrome v0.169 ZEB2 Achchuthan Shanmugasundram Mode of inheritance for gene: ZEB2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Paediatric pseudo-obstruction syndrome v0.168 ZEB2 Achchuthan Shanmugasundram Classified gene: ZEB2 as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.168 ZEB2 Achchuthan Shanmugasundram Gene: zeb2 has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.167 ZEB2 Achchuthan Shanmugasundram reviewed gene: ZEB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 11279515; Phenotypes: Mowat-Wilson syndrome, OMIM:235730; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Paediatric pseudo-obstruction syndrome v0.167 TYMP Achchuthan Shanmugasundram Phenotypes for gene: TYMP were changed from to Mitochondrial DNA depletion syndrome 1 (MNGIE type), OMIM:603041
Paediatric pseudo-obstruction syndrome v0.166 TYMP Achchuthan Shanmugasundram Publications for gene: TYMP were set to
Paediatric pseudo-obstruction syndrome v0.165 TYMP Achchuthan Shanmugasundram Mode of inheritance for gene: TYMP was changed from to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.164 TYMP Achchuthan Shanmugasundram Classified gene: TYMP as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.164 TYMP Achchuthan Shanmugasundram Gene: tymp has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.163 TYMP Achchuthan Shanmugasundram reviewed gene: TYMP: Rating: GREEN; Mode of pathogenicity: None; Publications: 31848803, 32898308, 33825174; Phenotypes: Mitochondrial DNA depletion syndrome 1 (MNGIE type), OMIM:603041; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.163 TWNK Achchuthan Shanmugasundram Phenotypes for gene: TWNK were changed from to Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), OMIM:271245; Perrault syndrome 5, OMIM:616138
Paediatric pseudo-obstruction syndrome v0.162 TWNK Achchuthan Shanmugasundram Mode of inheritance for gene: TWNK was changed from to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.161 TWNK Achchuthan Shanmugasundram Publications for gene: TWNK were set to
Paediatric pseudo-obstruction syndrome v0.160 TWNK Achchuthan Shanmugasundram reviewed gene: TWNK: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), OMIM:271245, Perrault syndrome 5, OMIM:616138; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.160 TTC7A Achchuthan Shanmugasundram Phenotypes for gene: TTC7A were changed from to Gastrointestinal defects and immunodeficiency syndrome, OMIM:243150
Paediatric pseudo-obstruction syndrome v0.159 TTC7A Achchuthan Shanmugasundram Publications for gene: TTC7A were set to
Paediatric pseudo-obstruction syndrome v0.158 TTC7A Achchuthan Shanmugasundram Mode of inheritance for gene: TTC7A was changed from to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.157 TTC7A Achchuthan Shanmugasundram Classified gene: TTC7A as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.157 TTC7A Achchuthan Shanmugasundram Gene: ttc7a has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.156 TTC7A Achchuthan Shanmugasundram reviewed gene: TTC7A: Rating: GREEN; Mode of pathogenicity: None; Publications: 31787977, 34975848, 34985046, 35627206; Phenotypes: Gastrointestinal defects and immunodeficiency syndrome, OMIM:243150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.156 TK2 Achchuthan Shanmugasundram Classified gene: TK2 as Red List (low evidence)
Paediatric pseudo-obstruction syndrome v0.156 TK2 Achchuthan Shanmugasundram Gene: tk2 has been classified as Red List (Low Evidence).
Paediatric pseudo-obstruction syndrome v0.155 TK2 Achchuthan Shanmugasundram edited their review of gene: TK2: Added comment: Comment on list classification: This gene should be rated RED as I do not see any association of this gene with intestinal dysmotility and pseudo-obstruction.

This gene has been associated with mitochondrial DNA depletion syndrome 2 (myopathic type) (MIM #609560) in OMIM. However, this disorder is characterised by hypotonia and muscle weakness, facial weakness, bulbar weakness (dysarthria and dysphagia) and elevated serum creatine phosphokinase. I do not see any clear indication of links of this disorder with either pseudo-obstruction or intestinal dysmotility.; Changed rating: RED
Paediatric pseudo-obstruction syndrome v0.155 TK2 Achchuthan Shanmugasundram Deleted their comment
Paediatric pseudo-obstruction syndrome v0.155 SUCLG1 Achchuthan Shanmugasundram Classified gene: SUCLG1 as Red List (low evidence)
Paediatric pseudo-obstruction syndrome v0.155 SUCLG1 Achchuthan Shanmugasundram Gene: suclg1 has been classified as Red List (Low Evidence).
Paediatric pseudo-obstruction syndrome v0.154 SUCLG1 Achchuthan Shanmugasundram edited their review of gene: SUCLG1: Added comment: Comment on list classification: This gene should be rated RED as I do not see any association of this gene with intestinal dysmotility and pseudo-obstruction.

This gene has been associated with mitochondrial DNA depletion syndrome 9 (encephalomyopathic with or without methylmalonic aciduria) (MIM #245400) in OMIM. However, this disorder is characterised by infantile onset of hypotonia, lactic acidosis, severe psychomotor retardation, progressive neurologic deterioration, and excretion of methylmalonic acid. Although other frequent manifestations include feeding difficulty and gastroesophageal reflux, there is no clear indication of any links of this disorder with either pseudo-obstruction or intestinal dysmotility.; Changed rating: RED
Paediatric pseudo-obstruction syndrome v0.154 SUCLG1 Achchuthan Shanmugasundram Deleted their comment
Paediatric pseudo-obstruction syndrome v0.154 SUCLA2 Achchuthan Shanmugasundram Classified gene: SUCLA2 as Red List (low evidence)
Paediatric pseudo-obstruction syndrome v0.154 SUCLA2 Achchuthan Shanmugasundram Gene: sucla2 has been classified as Red List (Low Evidence).
Paediatric pseudo-obstruction syndrome v0.153 SUCLA2 Achchuthan Shanmugasundram edited their review of gene: SUCLA2: Added comment: Comment on list classification: This gene should be rated RED as I do not see any association of this gene with intestinal dysmotility and pseudo-obstruction.

This gene has been associated with mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria) (MIM #612073) in OMIM. However, this disorder is characterised by infantile onset of hypotonia, progressive neurologic deterioration, a hyperkinetic-dystonic movement disorder, external ophthalmoplegia, deafness, variable renal tubular dysfunction, and mild methylmalonic aciduria. Although other frequent manifestations include feeding difficulty and gastroesophageal reflux, there is no clear indication of any links of this disorder with either pseudo-obstruction or intestinal dysmotility.; Changed rating: RED
Paediatric pseudo-obstruction syndrome v0.153 SUCLA2 Achchuthan Shanmugasundram Deleted their comment
Paediatric pseudo-obstruction syndrome v0.153 MPV17 Achchuthan Shanmugasundram Phenotypes for gene: MPV17 were changed from Mitochondrial DNA depletion syndrome 6 (hepatocerebral type); OMIM:256810 to Mitochondrial DNA depletion syndrome 6 (hepatocerebral type), OMIM:256810
Paediatric pseudo-obstruction syndrome v0.152 MPV17 Achchuthan Shanmugasundram edited their review of gene: MPV17: Changed phenotypes to: Mitochondrial DNA depletion syndrome 6 (hepatocerebral type), OMIM:256810
Paediatric pseudo-obstruction syndrome v0.152 MPV17 Achchuthan Shanmugasundram changed review comment from: Comment on rating: The rating should be GREEN as this gene has been implicated in Navajo neurohepatopathy (MIM #256810) from multiple (>3) unrelated cases, and supported by functional studies.

PMID:35750291 recently reported two patients from unrelated families with different variants from MPV17 gene.

PMID:29282788 summarised the clinical features of 100 affected individuals with a total of 48 pathogenic variants in MPV17 gene, of which 25 new individuals with nine novel variants were reported in this publication.

This gene-disease association was already reported in both OMIM and G2P.; to: Comment on rating: The rating should be GREEN as this gene has been implicated in Navajo neurohepatopathy (MIM #256810) from multiple (>3) unrelated cases, and supported by functional studies.

PMID:35750291 recently reported two patients from unrelated families with different variants from MPV17 gene.

PMID:29282788 summarised the clinical features of 100 affected individuals with a total of 48 pathogenic variants in MPV17 gene, of which 25 new individuals with nine novel variants were reported in this publication. About a third of these individuals have feeding difficulties and gastrointestinal dysmotility manifesting as gastroesophagal reflux, recurrent vomiting, and diarrhoea.

This gene-disease association was already reported in both OMIM and G2P.
Paediatric pseudo-obstruction syndrome v0.152 TPM3 Achchuthan Shanmugasundram reviewed gene: TPM3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Paediatric pseudo-obstruction syndrome v0.152 TK2 Achchuthan Shanmugasundram Phenotypes for gene: TK2 were changed from to Mitochondrial DNA depletion syndrome 2 (myopathic type), OMIM:609560
Paediatric pseudo-obstruction syndrome v0.151 TK2 Achchuthan Shanmugasundram Publications for gene: TK2 were set to
Paediatric pseudo-obstruction syndrome v0.150 TK2 Achchuthan Shanmugasundram Mode of inheritance for gene: TK2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.149 TK2 Achchuthan Shanmugasundram Classified gene: TK2 as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.149 TK2 Achchuthan Shanmugasundram Gene: tk2 has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.148 TK2 Achchuthan Shanmugasundram reviewed gene: TK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23385875; Phenotypes: Mitochondrial DNA depletion syndrome 2 (myopathic type), OMIM:609560; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.148 SURF1 Achchuthan Shanmugasundram Phenotypes for gene: SURF1 were changed from to Mitochondrial complex IV deficiency, nuclear type 1, OMIM:220110
Paediatric pseudo-obstruction syndrome v0.147 SURF1 Achchuthan Shanmugasundram edited their review of gene: SURF1: Changed phenotypes to: Mitochondrial complex IV deficiency, nuclear type 1, OMIM:220110
Paediatric pseudo-obstruction syndrome v0.147 SURF1 Achchuthan Shanmugasundram reviewed gene: SURF1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Paediatric pseudo-obstruction syndrome v0.147 SUCLG1 Achchuthan Shanmugasundram Phenotypes for gene: SUCLG1 were changed from to Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria), OMIM:245400
Paediatric pseudo-obstruction syndrome v0.146 SUCLG1 Achchuthan Shanmugasundram Publications for gene: SUCLG1 were set to
Paediatric pseudo-obstruction syndrome v0.145 SUCLG1 Achchuthan Shanmugasundram Mode of inheritance for gene: SUCLG1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.144 SUCLG1 Achchuthan Shanmugasundram Classified gene: SUCLG1 as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.144 SUCLG1 Achchuthan Shanmugasundram Gene: suclg1 has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.143 SUCLG1 Achchuthan Shanmugasundram edited their review of gene: SUCLG1: Changed rating: GREEN
Paediatric pseudo-obstruction syndrome v0.143 SUCLG1 Achchuthan Shanmugasundram reviewed gene: SUCLG1: Rating: ; Mode of pathogenicity: None; Publications: 19526370, 20453710, 23385875, 26028457, 33230783, 35762302; Phenotypes: Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria), OMIM:245400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.143 SUCLA2 Achchuthan Shanmugasundram Phenotypes for gene: SUCLA2 were changed from to Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), OMIM:612073
Paediatric pseudo-obstruction syndrome v0.142 SUCLA2 Achchuthan Shanmugasundram Publications for gene: SUCLA2 were set to
Paediatric pseudo-obstruction syndrome v0.141 SUCLA2 Achchuthan Shanmugasundram Mode of inheritance for gene: SUCLA2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.140 SUCLA2 Achchuthan Shanmugasundram Classified gene: SUCLA2 as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.140 SUCLA2 Achchuthan Shanmugasundram Gene: sucla2 has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.139 SUCLA2 Achchuthan Shanmugasundram reviewed gene: SUCLA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23385875; Phenotypes: Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria), OMIM:612073; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.139 SOX10 Achchuthan Shanmugasundram Phenotypes for gene: SOX10 were changed from to PCWH syndrome, OMIM:609136; Waardenburg syndrome, type 4C, OMIM:613266
Paediatric pseudo-obstruction syndrome v0.138 SOX10 Achchuthan Shanmugasundram Publications for gene: SOX10 were set to
Paediatric pseudo-obstruction syndrome v0.137 SOX10 Achchuthan Shanmugasundram Mode of inheritance for gene: SOX10 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.136 SOX10 Achchuthan Shanmugasundram Classified gene: SOX10 as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.136 SOX10 Achchuthan Shanmugasundram Gene: sox10 has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.135 SOX10 Achchuthan Shanmugasundram reviewed gene: SOX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 12189494; Phenotypes: PCWH syndrome, OMIM:609136, Waardenburg syndrome, type 4C, OMIM:613266; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.135 SGO1 Achchuthan Shanmugasundram Phenotypes for gene: SGO1 were changed from to Chronic atrial and intestinal dysrhythmia, OMIM:616201
Paediatric pseudo-obstruction syndrome v0.134 SGO1 Achchuthan Shanmugasundram Publications for gene: SGO1 were set to
Paediatric pseudo-obstruction syndrome v0.133 SGO1 Achchuthan Shanmugasundram Mode of inheritance for gene: SGO1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.132 SGO1 Achchuthan Shanmugasundram Classified gene: SGO1 as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.132 SGO1 Achchuthan Shanmugasundram Gene: sgo1 has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.131 SGO1 Achchuthan Shanmugasundram reviewed gene: SGO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 25282101, 31848803; Phenotypes: Chronic atrial and intestinal dysrhythmia, OMIM:616201; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.131 SEMA3F Achchuthan Shanmugasundram Publications for gene: SEMA3F were set to
Paediatric pseudo-obstruction syndrome v0.130 SEMA3F Achchuthan Shanmugasundram Phenotypes for gene: SEMA3F were changed from to megacolon, MONDO:0001273
Paediatric pseudo-obstruction syndrome v0.129 SEMA3F Achchuthan Shanmugasundram Mode of inheritance for gene: SEMA3F was changed from to Unknown
Paediatric pseudo-obstruction syndrome v0.128 SEMA3F Achchuthan Shanmugasundram reviewed gene: SEMA3F: Rating: RED; Mode of pathogenicity: None; Publications: 30663199; Phenotypes: megacolon, MONDO:0001273; Mode of inheritance: None
Paediatric pseudo-obstruction syndrome v0.128 SDHA Achchuthan Shanmugasundram edited their review of gene: SDHA: Changed rating: RED
Paediatric pseudo-obstruction syndrome v0.128 SDHA Achchuthan Shanmugasundram commented on gene: SDHA
Paediatric pseudo-obstruction syndrome v0.128 SCN10A Achchuthan Shanmugasundram reviewed gene: SCN10A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Paediatric pseudo-obstruction syndrome v0.128 RRM2B Achchuthan Shanmugasundram Phenotypes for gene: RRM2B were changed from to Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy), OMIM:612075; Mitochondrial DNA depletion syndrome 8B (MNGIE type), OMIM:612075
Paediatric pseudo-obstruction syndrome v0.127 RRM2B Achchuthan Shanmugasundram Publications for gene: RRM2B were set to
Paediatric pseudo-obstruction syndrome v0.126 RRM2B Achchuthan Shanmugasundram Mode of inheritance for gene: RRM2B was changed from to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.125 RRM2B Achchuthan Shanmugasundram changed review comment from: Comment on list classification: This gene should be rated RED as this gene was associated with mitochondrial DNA depletion syndrome 8B (MNGIE type) (#612075) from only one patient from PMID:19667227.

This adult patient exhibited clinical findings strongly suggestive for MNGIE such as gastrointestinal dysmotility, cachexia and peripheral neuropathy. This patient also showed severe mtDNA depletion in muscle tissue and was identified with two variants in the RRM2B gene.

Although gastrointestinal phenotypes are found in some of the patients with mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy) (10 out of 31), these are limited to recurrent vomiting, feed intolerance, chronic diarrhea and cachexia and none of them had gastrointestinal dysmotility or pseudo-obstruction.

This gene is associated with relevant phenotypes in both OMIM and G2P.; to: Comment on list classification: This gene should be rated RED as this gene was associated with mitochondrial DNA depletion syndrome 8B (MNGIE type) (#612075) from only one patient from PMID:19667227.

This adult patient exhibited clinical findings strongly suggestive for MNGIE such as gastrointestinal dysmotility, cachexia and peripheral neuropathy. This patient also showed severe mtDNA depletion in muscle tissue and was identified with two variants in the RRM2B gene.

Although gastrointestinal phenotypes are found in some of the patients with mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy) (10 out of 31), these are limited to recurrent vomiting, feed intolerance, chronic diarrhea and cachexia and none of them had gastrointestinal dysmotility or pseudo-obstruction (PMID:24741716).

This gene is associated with relevant phenotypes in both OMIM and G2P.
Paediatric pseudo-obstruction syndrome v0.125 RRM2B Achchuthan Shanmugasundram edited their review of gene: RRM2B: Changed publications to: 19667227, 23385875, 24741716
Paediatric pseudo-obstruction syndrome v0.125 RRM2B Achchuthan Shanmugasundram reviewed gene: RRM2B: Rating: RED; Mode of pathogenicity: None; Publications: 19667227, 23385875; Phenotypes: Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy), OMIM:612075, Mitochondrial DNA depletion syndrome 8B (MNGIE type), OMIM:612075; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.125 RET Achchuthan Shanmugasundram Phenotypes for gene: RET were changed from to {Hirschsprung disease, susceptibility to, 1}, 142623; {Hirschsprung disease, protection against}, 142623
Paediatric pseudo-obstruction syndrome v0.124 RET Achchuthan Shanmugasundram Publications for gene: RET were set to
Paediatric pseudo-obstruction syndrome v0.123 RET Achchuthan Shanmugasundram Mode of inheritance for gene: RET was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.122 RET Achchuthan Shanmugasundram Classified gene: RET as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.122 RET Achchuthan Shanmugasundram Gene: ret has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.121 RET Achchuthan Shanmugasundram reviewed gene: RET: Rating: GREEN; Mode of pathogenicity: None; Publications: 21960833, 31848803, 34092334, 36521661; Phenotypes: {Hirschsprung disease, susceptibility to, 1}, 142623, {Hirschsprung disease, protection against}, 142623; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.121 RAD21 Achchuthan Shanmugasundram Phenotypes for gene: RAD21 were changed from to Mungan syndrome, OMIM:611376
Paediatric pseudo-obstruction syndrome v0.120 RAD21 Achchuthan Shanmugasundram Publications for gene: RAD21 were set to
Paediatric pseudo-obstruction syndrome v0.119 RAD21 Achchuthan Shanmugasundram Mode of inheritance for gene: RAD21 was changed from to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.118 RAD21 Achchuthan Shanmugasundram Classified gene: RAD21 as Amber List (moderate evidence)
Paediatric pseudo-obstruction syndrome v0.118 RAD21 Achchuthan Shanmugasundram Gene: rad21 has been classified as Amber List (Moderate Evidence).
Paediatric pseudo-obstruction syndrome v0.117 RAD21 Achchuthan Shanmugasundram Classified gene: RAD21 as Amber List (moderate evidence)
Paediatric pseudo-obstruction syndrome v0.117 RAD21 Achchuthan Shanmugasundram Gene: rad21 has been classified as Amber List (Moderate Evidence).
Paediatric pseudo-obstruction syndrome v0.116 RAD21 Achchuthan Shanmugasundram reviewed gene: RAD21: Rating: AMBER; Mode of pathogenicity: None; Publications: 14638363, 21832993, 25575569, 31848803, 32687945; Phenotypes: Mungan syndrome, OMIM:611376; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.116 PROKR2 Achchuthan Shanmugasundram Phenotypes for gene: PROKR2 were changed from to Hirschsprung disease, MONDO:0018309
Paediatric pseudo-obstruction syndrome v0.115 PROKR2 Achchuthan Shanmugasundram Publications for gene: PROKR2 were set to
Paediatric pseudo-obstruction syndrome v0.114 PROKR2 Achchuthan Shanmugasundram Mode of inheritance for gene: PROKR2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.113 PROKR2 Achchuthan Shanmugasundram Classified gene: PROKR2 as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.113 PROKR2 Achchuthan Shanmugasundram Gene: prokr2 has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.112 PROKR2 Achchuthan Shanmugasundram reviewed gene: PROKR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 21858136; Phenotypes: Hirschsprung disease, MONDO:0018309; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.112 PROKR1 Achchuthan Shanmugasundram Phenotypes for gene: PROKR1 were changed from to Hirschsprung disease, MONDO:0018309
Paediatric pseudo-obstruction syndrome v0.111 PROKR1 Achchuthan Shanmugasundram Publications for gene: PROKR1 were set to
Paediatric pseudo-obstruction syndrome v0.110 PROKR1 Achchuthan Shanmugasundram Mode of inheritance for gene: PROKR1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.109 PROKR1 Achchuthan Shanmugasundram Classified gene: PROKR1 as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.109 PROKR1 Achchuthan Shanmugasundram Gene: prokr1 has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.108 PROKR1 Achchuthan Shanmugasundram reviewed gene: PROKR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21858136; Phenotypes: Hirschsprung disease, MONDO:0018309; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.108 PROK1 Achchuthan Shanmugasundram Phenotypes for gene: PROK1 were changed from to Hirschsprung disease, MONDO:0018309
Paediatric pseudo-obstruction syndrome v0.107 PROK1 Achchuthan Shanmugasundram Publications for gene: PROK1 were set to
Paediatric pseudo-obstruction syndrome v0.106 PROK1 Achchuthan Shanmugasundram Mode of inheritance for gene: PROK1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.105 PROK1 Achchuthan Shanmugasundram Classified gene: PROK1 as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.105 PROK1 Achchuthan Shanmugasundram Gene: prok1 has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.104 PROK1 Achchuthan Shanmugasundram reviewed gene: PROK1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21858136; Phenotypes: Hirschsprung disease, MONDO:0018309; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.104 POLG Achchuthan Shanmugasundram Phenotypes for gene: POLG were changed from to Mitochondrial DNA depletion syndrome 4B (MNGIE type), OMIM:613662
Paediatric pseudo-obstruction syndrome v0.103 POLG Achchuthan Shanmugasundram Publications for gene: POLG were set to
Paediatric pseudo-obstruction syndrome v0.102 POLG Achchuthan Shanmugasundram Mode of inheritance for gene: POLG was changed from to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.101 POLG Achchuthan Shanmugasundram Classified gene: POLG as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.101 POLG Achchuthan Shanmugasundram Gene: polg has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.100 POLG Achchuthan Shanmugasundram reviewed gene: POLG: Rating: GREEN; Mode of pathogenicity: None; Publications: 12825077, 19307547, 21993618, 23385875, 31848803; Phenotypes: Mitochondrial DNA depletion syndrome 4B (MNGIE type), OMIM:613662; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.100 PDCL3 Achchuthan Shanmugasundram Phenotypes for gene: PDCL3 were changed from to Megacystis-microcolon-intestinal hypoperistalsis syndrome, MONDO:0025986
Paediatric pseudo-obstruction syndrome v0.99 PDCL3 Achchuthan Shanmugasundram Publications for gene: PDCL3 were set to
Paediatric pseudo-obstruction syndrome v0.98 PDCL3 Achchuthan Shanmugasundram Mode of inheritance for gene: PDCL3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.97 PDCL3 Achchuthan Shanmugasundram reviewed gene: PDCL3: Rating: RED; Mode of pathogenicity: None; Publications: 32621347; Phenotypes: megacystis-microcolon-intestinal hypoperistalsis syndrome, MONDO:0025986; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.97 NKX2-1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: Not associated with any relevant phenotype in OMIM or G2P. PMID:30663199 does not report any cases associated with NKX2-1 and a quick literature search did not find any literature making an association. So, this gene should be rated as RED.; to: Comment on list classification: The phenotypes that are reported in OMIM or G2P are not relevant to this panel. PMID:30663199 does not report any cases associated with NKX2-1 and a quick literature search did not find any literature making an association. So, this gene should be rated as RED.
Paediatric pseudo-obstruction syndrome v0.97 NRTN Achchuthan Shanmugasundram reviewed gene: NRTN: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Paediatric pseudo-obstruction syndrome v0.97 NKX2-1 Achchuthan Shanmugasundram reviewed gene: NKX2-1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Paediatric pseudo-obstruction syndrome v0.97 NDUFS1 Achchuthan Shanmugasundram reviewed gene: NDUFS1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Paediatric pseudo-obstruction syndrome v0.97 MYLK Achchuthan Shanmugasundram Phenotypes for gene: MYLK were changed from to Megacystis-microcolon-intestinal hypoperistalsis syndrome 1, OMIM:249210
Paediatric pseudo-obstruction syndrome v0.96 MYLK Achchuthan Shanmugasundram Publications for gene: MYLK were set to
Paediatric pseudo-obstruction syndrome v0.95 MYLK Achchuthan Shanmugasundram Mode of inheritance for gene: MYLK was changed from to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.94 MYLK Achchuthan Shanmugasundram Classified gene: MYLK as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.94 MYLK Achchuthan Shanmugasundram Gene: mylk has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.93 MYLK Achchuthan Shanmugasundram reviewed gene: MYLK: Rating: GREEN; Mode of pathogenicity: None; Publications: 28602422, 31848803, 33729000; Phenotypes: Megacystis-microcolon-intestinal hypoperistalsis syndrome 1, OMIM:249210; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.93 MYL9 Achchuthan Shanmugasundram Phenotypes for gene: MYL9 were changed from to Megacystis-microcolon-intestinal hypoperistalsis syndrome 4, OMIM:619365
Paediatric pseudo-obstruction syndrome v0.92 MYL9 Achchuthan Shanmugasundram Publications for gene: MYL9 were set to
Paediatric pseudo-obstruction syndrome v0.91 MYL9 Achchuthan Shanmugasundram Mode of inheritance for gene: MYL9 was changed from to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.90 MYL9 Achchuthan Shanmugasundram Classified gene: MYL9 as Amber List (moderate evidence)
Paediatric pseudo-obstruction syndrome v0.90 MYL9 Achchuthan Shanmugasundram Gene: myl9 has been classified as Amber List (Moderate Evidence).
Paediatric pseudo-obstruction syndrome v0.89 MYL9 Achchuthan Shanmugasundram reviewed gene: MYL9: Rating: AMBER; Mode of pathogenicity: None; Publications: 27481187, 31848803, 33031641, 33729000; Phenotypes: Megacystis-microcolon-intestinal hypoperistalsis syndrome 4, OMIM:619365; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.89 MYH11 Achchuthan Shanmugasundram Phenotypes for gene: MYH11 were changed from to Megacystis-microcolon-intestinal hypoperistalsis syndrome 2, OMIM:619351; Visceral myopathy 2, OMIM:619350
Paediatric pseudo-obstruction syndrome v0.88 MYH11 Achchuthan Shanmugasundram Publications for gene: MYH11 were set to
Paediatric pseudo-obstruction syndrome v0.87 MYH11 Achchuthan Shanmugasundram Mode of inheritance for gene: MYH11 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.86 MYH11 Achchuthan Shanmugasundram edited their review of gene: MYH11: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.86 MYH11 Achchuthan Shanmugasundram Classified gene: MYH11 as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.86 MYH11 Achchuthan Shanmugasundram Gene: myh11 has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.85 MYH11 Achchuthan Shanmugasundram reviewed gene: MYH11: Rating: GREEN; Mode of pathogenicity: None; Publications: 25407000, 29575632, 31044419, 31389005, 31427716, 31848803, 31944481, 33729000; Phenotypes: Megacystis-microcolon-intestinal hypoperistalsis syndrome 2, OMIM:619351, Visceral myopathy 2, OMIM:619350; Mode of inheritance: None
Paediatric pseudo-obstruction syndrome v0.85 MPV17 Achchuthan Shanmugasundram Phenotypes for gene: MPV17 were changed from to Mitochondrial DNA depletion syndrome 6 (hepatocerebral type); OMIM:256810
Paediatric pseudo-obstruction syndrome v0.84 MPV17 Achchuthan Shanmugasundram Publications for gene: MPV17 were set to
Paediatric pseudo-obstruction syndrome v0.83 MPV17 Achchuthan Shanmugasundram Classified gene: MPV17 as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.83 MPV17 Achchuthan Shanmugasundram Gene: mpv17 has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.82 MPV17 Achchuthan Shanmugasundram reviewed gene: MPV17: Rating: GREEN; Mode of pathogenicity: None; Publications: 23385875, 29282788, 35750291; Phenotypes: Mitochondrial DNA depletion syndrome 6 (hepatocerebral type), OMIM:256810; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.28 TUBB2B Arina Puzriakova Phenotypes for gene: TUBB2B were changed from Polymicrogyria, symmetric or asymmetric, 610031; POLYMICROGYRIA ASYMMETRIC (PMGA) to Cortical dysplasia, complex, with other brain malformations 7, OMIM:610031
Hereditary ataxia with onset in adulthood v3.6 TUBB2B Arina Puzriakova Phenotypes for gene: TUBB2B were changed from Complex cortical dysplasia with other brain abnormalities 7, 610031 to Cortical dysplasia, complex, with other brain malformations 7, OMIM:610031
Early onset or syndromic epilepsy v3.19 TUBB2B Arina Puzriakova Phenotypes for gene: TUBB2B were changed from Cortical dysplasia, complex, with other brain malformations 7, 610031 to Cortical dysplasia, complex, with other brain malformations 7, OMIM:610031
Fetal anomalies v2.8 TUBB2B Arina Puzriakova Phenotypes for gene: TUBB2B were changed from POLYMICROGYRIA ASYMMETRIC to Cortical dysplasia, complex, with other brain malformations 7, OMIM:610031
Cerebellar hypoplasia v1.72 TUBB2B Arina Puzriakova Phenotypes for gene: TUBB2B were changed from complex cortical dysplasia with other brain malformations-7 , 610031 to Cortical dysplasia, complex, with other brain malformations 7, OMIM:610031
Malformations of cortical development v3.9 TUBB2B Arina Puzriakova Phenotypes for gene: TUBB2B were changed from Polymicrogyria, symmetric or asymmetric 610031 to Cortical dysplasia, complex, with other brain malformations 7, OMIM:610031
Ataxia and cerebellar anomalies - narrow panel v3.21 TUBB2B Arina Puzriakova Phenotypes for gene: TUBB2B were changed from complex cortical dysplasia with other brain malformations-7 , 610031 to Cortical dysplasia, complex, with other brain malformations 7, OMIM:610031
Adult onset leukodystrophy v2.3 PRNP Eleanor Williams changed review comment from: Review submitted on behalf of David Lynch, James Polke, Henry Houlden, Lucy Jenkins. Mode of inheritance: AD. Phenotype: Cerebral amyloid angiopathy,PRNP-related. Evidence: MIM: 137440.; to: Review submitted on behalf of David Lynch, James Polke, Henry Houlden, Lucy Jenkins. Mode of inheritance: AD. Phenotype: Cerebral amyloid angiopathy, PRNP-related. Evidence: MIM: 137440.
Adult onset leukodystrophy v2.3 TTR Eleanor Williams reviewed gene: TTR: Rating: ; Mode of pathogenicity: ; Publications: 25802113, 31257920, 27466465, 34663645, 28991667, 35040071, 29779881, 34390072; Phenotypes: Cerebral amyloid angiopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset leukodystrophy v2.3 LAMB1 Eleanor Williams reviewed gene: LAMB1: Rating: ; Mode of pathogenicity: ; Publications: 34606115; Phenotypes: Cerebral small vessel disease, with leukoencephalopathy and hippocampal memory impairment; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset leukodystrophy v2.3 PSEN2 Eleanor Williams reviewed gene: PSEN2: Rating: ; Mode of pathogenicity: ; Publications: 9450781; Phenotypes: PSEN2 related cerebral amyloid angiopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset leukodystrophy v2.3 PSEN1 Eleanor Williams reviewed gene: PSEN1: Rating: ; Mode of pathogenicity: ; Publications: 34319632, 26888304, 11489138, 11395394; Phenotypes: PSEN1 related cerebral amyloid angiopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset leukodystrophy v2.3 PRNP Eleanor Williams reviewed gene: PRNP: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Cerebral amyloid angiopathy,PRNP-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset leukodystrophy v2.3 GSN Eleanor Williams reviewed gene: GSN: Rating: ; Mode of pathogenicity: ; Publications: 25097823; Phenotypes: Hereditary gelsolin amyloidosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset leukodystrophy v2.3 ITM2B Eleanor Williams reviewed gene: ITM2B: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Familial British Dementia/Familial Danish Dementia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset leukodystrophy v2.3 CST3 Eleanor Williams reviewed gene: CST3: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Cerebral amyloid angiopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset leukodystrophy v2.3 APP Eleanor Williams reviewed gene: APP: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: CEREBRAL AMYLOID ANGIOPATHY,APP-RELATED; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset leukodystrophy v2.2 TTR Eleanor Williams gene: TTR was added
gene: TTR was added to White matter disorders - adult onset. Sources: Expert list
Mode of inheritance for gene: TTR was set to
Adult onset leukodystrophy v2.2 PSEN2 Eleanor Williams gene: PSEN2 was added
gene: PSEN2 was added to White matter disorders - adult onset. Sources: Expert list
Mode of inheritance for gene: PSEN2 was set to
Adult onset leukodystrophy v2.2 PSEN1 Eleanor Williams gene: PSEN1 was added
gene: PSEN1 was added to White matter disorders - adult onset. Sources: Expert list
Mode of inheritance for gene: PSEN1 was set to
Adult onset leukodystrophy v2.2 PRNP Eleanor Williams gene: PRNP was added
gene: PRNP was added to White matter disorders - adult onset. Sources: Expert list
Mode of inheritance for gene: PRNP was set to
Adult onset leukodystrophy v2.2 GSN Eleanor Williams gene: GSN was added
gene: GSN was added to White matter disorders - adult onset. Sources: Expert list
Mode of inheritance for gene: GSN was set to
Adult onset leukodystrophy v2.2 ITM2B Eleanor Williams gene: ITM2B was added
gene: ITM2B was added to White matter disorders - adult onset. Sources: Expert list
Mode of inheritance for gene: ITM2B was set to
Adult onset leukodystrophy v2.2 CST3 Eleanor Williams gene: CST3 was added
gene: CST3 was added to White matter disorders - adult onset. Sources: Expert list
Mode of inheritance for gene: CST3 was set to
Adult onset leukodystrophy v2.2 APP Eleanor Williams gene: APP was added
gene: APP was added to White matter disorders - adult onset. Sources: Expert list
Mode of inheritance for gene: APP was set to
Neurological segmental overgrowth v2.2 TBC1D7 Arina Puzriakova Phenotypes for gene: TBC1D7 were changed from MGCPH; Macrocephaly/megalencephaly syndrome, autosomal recessive, 248000 to Macrocephaly/megalencephaly syndrome, autosomal recessive, OMIM:248000
Intellectual disability v4.27 TBC1D7 Arina Puzriakova Phenotypes for gene: TBC1D7 were changed from intellectual disability; macrocephaly; megalencephaly to Macrocephaly/megalencephaly syndrome, autosomal recessive, OMIM:248000
Malformations of cortical development v3.8 SLC35A2 Arina Puzriakova Tag Q4_22_expert_review was removed from gene: SLC35A2.
Tag mosaicism tag was added to gene: SLC35A2.
Tag somatic tag was added to gene: SLC35A2.
Malformations of cortical development v3.8 SLC35A2 Arina Puzriakova Phenotypes for gene: SLC35A2 were changed from Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) to Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE); Congenital disorder of glycosylation, type IIm, OMIM:300896
Malformations of cortical development v3.7 SLC35A2 Arina Puzriakova Publications for gene: SLC35A2 were set to 33407896
Malformations of cortical development v3.6 SLC35A2 Arina Puzriakova Classified gene: SLC35A2 as Amber List (moderate evidence)
Malformations of cortical development v3.6 SLC35A2 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to support this gene-disease association and regardless of ability to detect somatic variants via this panel, there are enough cases with germline variants to warrant inclusion with a Green classification. Somatic cases should be picked up via other routes such as R429 'Mosaic brain disorders - deep sequencing' which is catered to somatic variant detection.
Malformations of cortical development v3.6 SLC35A2 Arina Puzriakova Gene: slc35a2 has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v3.5 SLC35A2 Arina Puzriakova Tag Q4_22_promote_green tag was added to gene: SLC35A2.
Tag Q4_22_expert_review tag was added to gene: SLC35A2.
Adult onset neurodegenerative disorder v3.4 TTR Eleanor Williams reviewed gene: TTR: Rating: ; Mode of pathogenicity: ; Publications: 29779881, 31257920, 34390072, 27466465, 35040071, 25802113, 34663645, 28991667; Phenotypes: Cerebral amyloid angiopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset neurodegenerative disorder v3.4 LAMB1 Eleanor Williams reviewed gene: LAMB1: Rating: ; Mode of pathogenicity: ; Publications: 34606115; Phenotypes: Cerebral small vessel disease, with leukoencephalopathy and hippocampal memory impairment; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset neurodegenerative disorder v3.4 GSN Eleanor Williams reviewed gene: GSN: Rating: ; Mode of pathogenicity: ; Publications: 25097823; Phenotypes: Hereditary gelsolin amyloidosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset neurodegenerative disorder v3.4 CST3 Eleanor Williams reviewed gene: CST3: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Cerebral amyloid angiopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset neurodegenerative disorder v3.4 TREX1 Eleanor Williams reviewed gene: TREX1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Vasculopathy, retinal, with cerebral leukoencephalopathy and systemic manifestations; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset neurodegenerative disorder v3.4 GLA Eleanor Williams reviewed gene: GLA: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Fabry disease; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Adult onset neurodegenerative disorder v3.4 COL4A2 Eleanor Williams reviewed gene: COL4A2: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Brain small vessel disease 2; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset neurodegenerative disorder v3.4 COL4A1 Eleanor Williams reviewed gene: COL4A1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Brain small vessel disease with or without ocular anomalies; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset neurodegenerative disorder v3.4 CTSA Eleanor Williams reviewed gene: CTSA: Rating: ; Mode of pathogenicity: ; Publications: 35904593, 28702507, 27664989; Phenotypes: Cathepsin A-related arteriopathy with strokes and leukoencephalopathy (CARASAL); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Adult onset neurodegenerative disorder v3.3 TTR Eleanor Williams gene: TTR was added
gene: TTR was added to Neurodegenerative disorders - adult onset. Sources: Expert list
Mode of inheritance for gene: TTR was set to
Adult onset neurodegenerative disorder v3.3 LAMB1 Eleanor Williams gene: LAMB1 was added
gene: LAMB1 was added to Neurodegenerative disorders - adult onset. Sources: Expert list
Mode of inheritance for gene: LAMB1 was set to
Adult onset neurodegenerative disorder v3.3 GSN Eleanor Williams gene: GSN was added
gene: GSN was added to Neurodegenerative disorders - adult onset. Sources: Expert list
Mode of inheritance for gene: GSN was set to
Adult onset neurodegenerative disorder v3.3 CST3 Eleanor Williams gene: CST3 was added
gene: CST3 was added to Neurodegenerative disorders - adult onset. Sources: Expert list
Mode of inheritance for gene: CST3 was set to
Adult onset neurodegenerative disorder v3.3 GLA Eleanor Williams gene: GLA was added
gene: GLA was added to Neurodegenerative disorders - adult onset. Sources: Expert list
Mode of inheritance for gene: GLA was set to
Adult onset neurodegenerative disorder v3.3 COL4A2 Eleanor Williams gene: COL4A2 was added
gene: COL4A2 was added to Neurodegenerative disorders - adult onset. Sources: Expert list
Mode of inheritance for gene: COL4A2 was set to
Adult onset neurodegenerative disorder v3.3 COL4A1 Eleanor Williams gene: COL4A1 was added
gene: COL4A1 was added to Neurodegenerative disorders - adult onset. Sources: Expert list
Mode of inheritance for gene: COL4A1 was set to
Adult onset neurodegenerative disorder v3.3 CTSA Eleanor Williams gene: CTSA was added
gene: CTSA was added to Neurodegenerative disorders - adult onset. Sources: Expert list
Mode of inheritance for gene: CTSA was set to
Paediatric pseudo-obstruction syndrome v0.82 PHOX2B Sarah Leigh Added comment: Comment on mode of inheritance: The mode of inheritance of both monoalleic and biallelic has been selected as PubMed: 30672101 reports a family where monoallelic family members are unaffected, but the compound heterozygous patient is affected.
Paediatric pseudo-obstruction syndrome v0.82 PHOX2B Sarah Leigh Mode of inheritance for gene: PHOX2B was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.81 PHOX2B Sarah Leigh Classified gene: PHOX2B as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.81 PHOX2B Sarah Leigh Gene: phox2b has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.80 PHOX2B Sarah Leigh reviewed gene: PHOX2B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Paediatric pseudo-obstruction syndrome v0.80 PHOX2B Sarah Leigh Publications for gene: PHOX2B were set to 30672101; 29543228; 12438263
Paediatric pseudo-obstruction syndrome v0.79 PHOX2B Sarah Leigh Publications for gene: PHOX2B were set to 30672101
Paediatric pseudo-obstruction syndrome v0.78 PHOX2B Sarah Leigh Phenotypes for gene: PHOX2B were changed from Central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, OMIM:209880; central hypoventilation syndrome, congenital, MONDO:0800031 to Central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, OMIM:209880; central hypoventilation syndrome, congenital, MONDO:0800031; Neuroblastoma with Hirschsprung disease, OMIM:613013; neuroblastoma, susceptibility to, 2, MONDO:0700041
Paediatric pseudo-obstruction syndrome v0.77 PHOX2B Sarah Leigh Mode of inheritance for gene: PHOX2B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.76 PHOX2B Sarah Leigh Publications for gene: PHOX2B were set to
Paediatric pseudo-obstruction syndrome v0.75 PHOX2B Sarah Leigh Phenotypes for gene: PHOX2B were changed from to Central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, OMIM:209880; central hypoventilation syndrome, congenital, MONDO:0800031
Paediatric pseudo-obstruction syndrome v0.74 PHOX2B Sarah Leigh Mode of inheritance for gene: PHOX2B was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Retinal disorders v3.6 POMGNT2 Eleanor Williams reviewed gene: POMGNT2: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Muscle Eye Brain disease, Walker Warburg disease, limb girdle muscular dystrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v3.6 POMGNT1 Eleanor Williams reviewed gene: POMGNT1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: non-syndromic Retinitis Pigmentosa, Walker Warburg syndrome, Muscle-eye-brain disease, dystroglycanopathy, retinal detachment; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v3.6 STN1 Eleanor Williams reviewed gene: STN1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Coats plus syndrome, cerebroretinal microangiopathy with calcifications and cysts; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v3.6 COL11A1 Eleanor Williams reviewed gene: COL11A1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Stickler syndrome, Marshall syndrome,, beaded vitreous, early onset hearing loss, retinal detachment; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Retinal disorders v3.6 COL9A3 Eleanor Williams reviewed gene: COL9A3: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: stickler syndrome, retinal degeneration, retinal detachment; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Retinal disorders v3.6 COL9A2 Eleanor Williams reviewed gene: COL9A2: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Stickler Syndrome, high myopia, retinal detachment,; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v3.6 COL9A1 Eleanor Williams reviewed gene: COL9A1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Stickler Syndrome, high myopia, retinal detachment, sensorineural hearing loss; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v3.6 COL2A1 Eleanor Williams reviewed gene: COL2A1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: retinal detachment, Stickler syndrome, cleft palate, hearing impairment, cataract,; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Retinal disorders v3.5 POMGNT2 Eleanor Williams gene: POMGNT2 was added
gene: POMGNT2 was added to Retinal disorders. Sources: Expert list
Mode of inheritance for gene: POMGNT2 was set to
Retinal disorders v3.5 STN1 Eleanor Williams gene: STN1 was added
gene: STN1 was added to Retinal disorders. Sources: Expert list
Mode of inheritance for gene: STN1 was set to
Retinal disorders v3.5 COL9A3 Eleanor Williams gene: COL9A3 was added
gene: COL9A3 was added to Retinal disorders. Sources: Expert list
Mode of inheritance for gene: COL9A3 was set to
Intellectual disability v4.26 PAFAH1B1 Arina Puzriakova Phenotypes for gene: PAFAH1B1 were changed from PAFAH1B1-Associated Lissencephaly/Subcortical Band Heterotopia; LISSENCEPHALY TYPE 1 (LIS1) to Lissencephaly 1, OMIM:607432; Subcortical laminar heterotopia, OMIM:607432
Early onset or syndromic epilepsy v3.18 PAFAH1B1 Arina Puzriakova Phenotypes for gene: PAFAH1B1 were changed from Lissencephaly 1 607432 to Lissencephaly 1, OMIM:607432; Subcortical laminar heterotopia, OMIM:607432
Fetal anomalies v2.7 PAFAH1B1 Arina Puzriakova Phenotypes for gene: PAFAH1B1 were changed from LISSENCEPHALY TYPE 1; SUBCORTICAL BAND HETEROTOPIA to Lissencephaly 1, OMIM:607432; Subcortical laminar heterotopia, OMIM:607432
Inherited white matter disorders v1.167 PAFAH1B1 Arina Puzriakova Phenotypes for gene: PAFAH1B1 were changed from Cerebral Malformation Disorders; Lissencephaly 1; Lissencephaly/Subcortical Band Heterotopia to Lissencephaly 1, OMIM:607432; Subcortical laminar heterotopia, OMIM:607432
Malformations of cortical development v3.5 PAFAH1B1 Arina Puzriakova Phenotypes for gene: PAFAH1B1 were changed from Lissencephaly 1 607432; Subcortical laminar heterotopia 607432 to Lissencephaly 1, OMIM:607432; Subcortical laminar heterotopia, OMIM:607432
White matter disorders and cerebral calcification - narrow panel v2.7 PAFAH1B1 Arina Puzriakova Phenotypes for gene: PAFAH1B1 were changed from Lissencephaly 1; Cerebral Malformation Disorders; Lissencephaly/Subcortical Band Heterotopia to Lissencephaly 1, OMIM:607432; Subcortical laminar heterotopia, OMIM:607432
Cerebral vascular malformations v2.66 PAFAH1B1 Arina Puzriakova Phenotypes for gene: PAFAH1B1 were changed from Cerebral Malformation Disorders to Lissencephaly 1, OMIM:607432; Subcortical laminar heterotopia, OMIM:607432
Early onset or syndromic epilepsy v3.17 NPRL2 Arina Puzriakova Phenotypes for gene: NPRL2 were changed from Epilepsy, familial focal, with variable foci 2, 617116 to Epilepsy, familial focal, with variable foci 2, OMIM:617116
Unexplained death in infancy and sudden unexplained death in childhood v3.0 Eleanor Williams Added Panel Unexplained death in infancy and childhood
Set child panels to: Genetic epilepsy syndromes; Inborn errors of metabolism; Long QT syndrome; Cardiomyopathies - including childhood onset
Set panel types to: Super Panel
Paediatric pseudo-obstruction syndrome v0.73 LMOD1 Achchuthan Shanmugasundram changed review comment from: Comment on classification of this gene: This gene should be rated GREEN, as this gene has been implicated in megacystis microcolon intestinal hypoperistalsis syndrome in two unrelated patients and is supported by evidence from mouse model.

A dutch female infant identified with homozygous nonsense variant (p.R370X) died at 5 days of life. Both her parents were heterozygous for the same variant. The clinical presentations include distended and lax abdominal wall, with palpable intestines, bladder distention, bilateral distention of the proximal ureters, and hydronephrosis (PMID:28292896).

A male infant with compound heterozygous missense variants (p.T369M; p.R421H) was also presented with typical symptoms of pediatric intestinal pseudo-obstruction (PIPO) but without megacystis and microcolon (PMID:35170814).

A mouse model with a similar Lmod1 mutation, engineered with CRISPR-Cas9 genome editing, exhibited the same gastrointestinal and urinary bladder phenotypes as seen in the dutch female infant (PMID:28292896).; to: Comment on classification of this gene: This gene should be rated GREEN, as this gene has been implicated in megacystis microcolon intestinal hypoperistalsis syndrome in two unrelated patients and is supported by evidence from mouse model.

A dutch female infant identified with homozygous nonsense variant (p.R370X) died at 5 days of life. Both her parents were heterozygous for the same variant. The clinical presentations include distended and lax abdominal wall, with palpable intestines, bladder distention, bilateral distention of the proximal ureters, and hydronephrosis (PMID:28292896).

A male infant with compound heterozygous missense variants (p.T369M; p.R421H) was also presented with typical symptoms of pediatric intestinal pseudo-obstruction (PIPO) but without megacystis and microcolon (PMID:35170814).

A mouse model with a similar Lmod1 mutation, engineered with CRISPR-Cas9 genome editing, exhibited the same gastrointestinal and urinary bladder phenotypes as seen in the dutch female infant (PMID:28292896).

This gene-disease association has already been reported in OMIM.
Paediatric pseudo-obstruction syndrome v0.73 LMOD1 Achchuthan Shanmugasundram Publications for gene: LMOD1 were set to
Paediatric pseudo-obstruction syndrome v0.72 LMOD1 Achchuthan Shanmugasundram Phenotypes for gene: LMOD1 were changed from to Megacystis-microcolon-intestinal hypoperistalsis syndrome 3, OMIM:619362
Paediatric pseudo-obstruction syndrome v0.71 LMOD1 Achchuthan Shanmugasundram Mode of inheritance for gene: LMOD1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.70 LMOD1 Achchuthan Shanmugasundram Classified gene: LMOD1 as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.70 LMOD1 Achchuthan Shanmugasundram Gene: lmod1 has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.69 LMOD1 Achchuthan Shanmugasundram reviewed gene: LMOD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28292896, 35170814; Phenotypes: Megacystis-microcolon-intestinal hypoperistalsis syndrome 3, OMIM:619362; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.25 DCX Arina Puzriakova Phenotypes for gene: DCX were changed from Lissencephaly, X-linked, 300067Subcortical laminal heteropia, X-linked, 300067; SUBCORTICAL BAND HETEROTOPIA X-LINKED (SBHX) to Lissencephaly, X-linked, OMIM:300067; Subcortical laminal heterotopia, X-linked, OMIM:300067
Early onset or syndromic epilepsy v3.16 DCX Arina Puzriakova Phenotypes for gene: DCX were changed from Lissencephaly, X-linked 300067; Subcortical laminal heterotopia, X-linked 300067 to Lissencephaly, X-linked, OMIM:300067; Subcortical laminal heterotopia, X-linked, OMIM:300067
Fetal anomalies v2.6 DCX Arina Puzriakova Phenotypes for gene: DCX were changed from SUBCORTICAL BAND HETEROTOPIA X-LINKED; LISSENCEPHALY X-LINKED TYPE 1 to Lissencephaly, X-linked, OMIM:300067; Subcortical laminal heterotopia, X-linked, OMIM:300067
Inherited white matter disorders v1.166 DCX Arina Puzriakova Phenotypes for gene: DCX were changed from Cerebral Malformation Disorders; Lissencephaly, X-Linked, 1; Classic Lissencephaly/Subcortical Band Heterotopia; Lissencephaly, X-linked, 300067; Subcortical laminal heteropia, X-linked, 300067 to Lissencephaly, X-linked, OMIM:300067; Subcortical laminal heterotopia, X-linked, OMIM:300067
Malformations of cortical development v3.4 DCX Arina Puzriakova Phenotypes for gene: DCX were changed from Lissencephaly, X-linked 300067; Subcortical laminal heteropia, X-linked 300067; Classic Lissencephaly/Subcortical Band Heterotopia to Lissencephaly, X-linked, OMIM:300067; Subcortical laminal heterotopia, X-linked, OMIM:300067
White matter disorders and cerebral calcification - narrow panel v2.6 DCX Arina Puzriakova Phenotypes for gene: DCX were changed from Lissencephaly, X-Linked, 1; Subcortical laminal heteropia, X-linked, 300067; Cerebral Malformation Disorders; Lissencephaly, X-linked, 300067; Classic Lissencephaly/Subcortical Band Heterotopia to Lissencephaly, X-linked, OMIM:300067; Subcortical laminal heterotopia, X-linked, OMIM:300067
Cerebral vascular malformations v2.65 DCX Arina Puzriakova Phenotypes for gene: DCX were changed from Cerebral Malformation Disorders to Lissencephaly, X-linked, OMIM:300067; Subcortical laminal heterotopia, X-linked, OMIM:300067
Cerebral vascular malformations v2.64 DCX Arina Puzriakova Mode of inheritance for gene: DCX was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Paediatric pseudo-obstruction syndrome v0.69 DGUOK Arina Puzriakova Mode of inheritance for gene: DGUOK was changed from to BIALLELIC, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v3.5 DDX3X Arina Puzriakova Classified gene: DDX3X as Amber List (moderate evidence)
Childhood onset hereditary spastic paraplegia v3.5 DDX3X Arina Puzriakova Gene: ddx3x has been classified as Amber List (Moderate Evidence).
Childhood onset hereditary spastic paraplegia v3.4 DDX3X Arina Puzriakova Publications for gene: DDX3X were set to
Childhood onset hereditary spastic paraplegia v3.3 DDX3X Arina Puzriakova Classified gene: DDX3X as Red List (low evidence)
Childhood onset hereditary spastic paraplegia v3.3 DDX3X Arina Puzriakova Gene: ddx3x has been classified as Red List (Low Evidence).
Childhood onset hereditary spastic paraplegia v3.2 DDX3X Arina Puzriakova changed review comment from: This gene is associated with a syndromic ID phenotype. A subset (~45%) of affected individuals develop movement disorders. This can comprise progressive spasticity which in some cases forms a presenting feature that is as key as ID, indicating that inclusion of DDX3X on this panel is likely to be beneficial in a diagnostic setting. Therefore, recommending that this gene is rated Green at the next GMS panel update.
Sources: Literature; to: This gene is associated with a syndromic ID phenotype. A subset (~45%) of affected individuals develop a movement disorder. This can comprise progressive spasticity which in some cases forms a presenting feature that is as key as ID, indicating that inclusion of DDX3X on this panel is likely to be beneficial in a diagnostic setting. Therefore, recommending that this gene is rated Green at the next GMS panel update.
Sources: Literature
Childhood onset hereditary spastic paraplegia v3.2 DDX3X Arina Puzriakova edited their review of gene: DDX3X: Changed publications to: 26235985, 29490693, 30936465, 32852922
Childhood onset hereditary spastic paraplegia v3.2 DDX3X Arina Puzriakova gene: DDX3X was added
gene: DDX3X was added to Hereditary spastic paraplegia - childhood onset. Sources: Literature
Q4_22_promote_green tags were added to gene: DDX3X.
Mode of inheritance for gene: DDX3X was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: DDX3X were set to Intellectual developmental disorder, X-linked syndromic, Snijders Blok type, OMIM:300958
Review for gene: DDX3X was set to GREEN
Added comment: This gene is associated with a syndromic ID phenotype. A subset (~45%) of affected individuals develop movement disorders. This can comprise progressive spasticity which in some cases forms a presenting feature that is as key as ID, indicating that inclusion of DDX3X on this panel is likely to be beneficial in a diagnostic setting. Therefore, recommending that this gene is rated Green at the next GMS panel update.
Sources: Literature
Paediatric pseudo-obstruction syndrome v0.68 DDX3X Arina Puzriakova Publications for gene: DDX3X were set to
Paediatric pseudo-obstruction syndrome v0.67 DDX3X Arina Puzriakova Classified gene: DDX3X as Red List (low evidence)
Paediatric pseudo-obstruction syndrome v0.67 DDX3X Arina Puzriakova Added comment: Comment on list classification: This gene is associated with a syndromic ID phenotype. Gastrointestinal disturbances were exhibited by one patient with severe constipation and a recurrent paralytic ileus (PMID: 32896648), and another patient with persistent gastro-oesophageal reflux (PMID: 30734472) although the latter isn't within the scope of this panel. Based on only one individual found displaying a phenotype that is relevant to this panel, recommending this gene is rated Red until further cases are reported. Cases are more likely to be picked up via other routes such as the ID panel.
Paediatric pseudo-obstruction syndrome v0.67 DDX3X Arina Puzriakova Gene: ddx3x has been classified as Red List (Low Evidence).
Paediatric pseudo-obstruction syndrome v0.66 LIG3 Achchuthan Shanmugasundram Phenotypes for gene: LIG3 were changed from to Mitochondrial DNA depletion syndrome 20 (MNGIE type), OMIM:619780
Paediatric pseudo-obstruction syndrome v0.65 LIG3 Achchuthan Shanmugasundram Publications for gene: LIG3 were set to
Paediatric pseudo-obstruction syndrome v0.64 LIG3 Achchuthan Shanmugasundram Mode of inheritance for gene: LIG3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.63 LIG3 Achchuthan Shanmugasundram Classified gene: LIG3 as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.63 LIG3 Achchuthan Shanmugasundram Gene: lig3 has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.62 LIG3 Achchuthan Shanmugasundram changed review comment from: Comment on rating: The rating should be GREEN as this gene has been implicated in mitochondrial neurogastrointestinal encephalomyopathy syndrome (MIM #619780) from seven patients from three unrelated families, and supported by functional studies.

These patients harboured compound heterozygous variants (family 1: p.K537N & p.G964R; family 2: p.C999Y & p.R267Ter; family 3: p.P609L & p.R811Ter) and their clinical phenotypes resembled the mitochondrial MINGE disease in many aspects. Severe dysmotility of the gut was present in all patients and most patients fulfilled the diagnostic criteria for CIPO.

Evidence from skeletal muscle biopsies from patients from all three families showed mitochondrial dysfunction. In vitro assays in patient-derived cells showed a decrease in LIG3 protein levels and ligase activity. In addition, LIG3 gene defects result in mitochondrial DNA depletion.

In vivo modelling of LIG3 mutations in zebrafish model also reproduced the brain alterations and impaired gut transit.; to: Comment on rating: The rating should be GREEN as this gene has been implicated in mitochondrial neurogastrointestinal encephalomyopathy syndrome (MIM #619780) from seven patients from three unrelated families, and supported by functional studies.

These patients harboured compound heterozygous variants (family 1: p.K537N & p.G964R; family 2: p.C999Y & p.R267Ter; family 3: p.P609L & p.R811Ter) and their clinical phenotypes resembled the mitochondrial MINGE disease in many aspects. Severe dysmotility of the gut was present in all patients and most patients fulfilled the diagnostic criteria for CIPO.

Evidence from skeletal muscle biopsies from patients from all three families showed mitochondrial dysfunction. In vitro assays in patient-derived cells showed a decrease in LIG3 protein levels and ligase activity. In addition, LIG3 gene defects result in mitochondrial DNA depletion.

In vivo modelling of LIG3 mutations in zebrafish model also reproduced the brain alterations and impaired gut transit.

This gene has already been reported in OMIM.
Paediatric pseudo-obstruction syndrome v0.62 LIG3 Achchuthan Shanmugasundram reviewed gene: LIG3: Rating: GREEN; Mode of pathogenicity: None; Publications: 33855352; Phenotypes: Mitochondrial DNA depletion syndrome 20 (MNGIE type), OMIM:619780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.24 DDX3X Arina Puzriakova Phenotypes for gene: DDX3X were changed from Intellectual disability, Mental retardation, X-linked 102, 300958 to Intellectual developmental disorder, X-linked syndromic, Snijders Blok type, OMIM:300958
Clefting v3.3 DDX3X Arina Puzriakova Phenotypes for gene: DDX3X were changed from MENTAL RETARDATION, X-LINKED 102; MRX102 to Intellectual developmental disorder, X-linked syndromic, Snijders Blok type, OMIM:300958
Fetal anomalies v2.5 DDX3X Arina Puzriakova Phenotypes for gene: DDX3X were changed from INTELLECTUAL DIABILITY; Intellectual disability; Mental retardation, X-linked 102, 300958 to Intellectual developmental disorder, X-linked syndromic, Snijders Blok type, OMIM:300958
Early onset or syndromic epilepsy v3.15 DDX3X Arina Puzriakova Phenotypes for gene: DDX3X were changed from Mental retardation, X-linked 102, 300958 to Intellectual developmental disorder, X-linked syndromic, Snijders Blok type, OMIM:300958
Paediatric pseudo-obstruction syndrome v0.62 DDX3X Arina Puzriakova Phenotypes for gene: DDX3X were changed from Intellectual developmental disorder, X-linked syndromic, Snijders Blok type 300958 to Intellectual developmental disorder, X-linked syndromic, Snijders Blok type, OMIM:300958
Paediatric pseudo-obstruction syndrome v0.61 DDX3X Arina Puzriakova Mode of inheritance for gene: DDX3X was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Paediatric pseudo-obstruction syndrome v0.60 DDX3X Arina Puzriakova Phenotypes for gene: DDX3X were changed from to Intellectual developmental disorder, X-linked syndromic, Snijders Blok type 300958
Paediatric pseudo-obstruction syndrome v0.59 COX15 Arina Puzriakova Classified gene: COX15 as Red List (low evidence)
Paediatric pseudo-obstruction syndrome v0.59 COX15 Arina Puzriakova Added comment: Comment on list classification: Could not find clear evidence linking this gene with intestinal pseudo-obstruction and therefore recommending Red gene rating at this time.
Paediatric pseudo-obstruction syndrome v0.59 COX15 Arina Puzriakova Gene: cox15 has been classified as Red List (Low Evidence).
Paediatric pseudo-obstruction syndrome v0.58 L1CAM Achchuthan Shanmugasundram commented on gene: L1CAM: Added a 'monogenic-polygenic' tag based on patient in PMID:22344793 who carried both L1CAM and RET variants.
Paediatric pseudo-obstruction syndrome v0.58 L1CAM Achchuthan Shanmugasundram Tag monogenic-polygenic tag was added to gene: L1CAM.
Paediatric pseudo-obstruction syndrome v0.58 L1CAM Achchuthan Shanmugasundram Classified gene: L1CAM as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.58 L1CAM Achchuthan Shanmugasundram Gene: l1cam has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.57 L1CAM Achchuthan Shanmugasundram Mode of inheritance for gene: L1CAM was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Paediatric pseudo-obstruction syndrome v0.56 L1CAM Achchuthan Shanmugasundram Phenotypes for gene: L1CAM were changed from to Hydrocephalus with congenital idiopathic intestinal pseudoobstruction, OMIM:307000
Paediatric pseudo-obstruction syndrome v0.55 L1CAM Achchuthan Shanmugasundram Publications for gene: L1CAM were set to
Paediatric pseudo-obstruction syndrome v0.54 L1CAM Achchuthan Shanmugasundram reviewed gene: L1CAM: Rating: GREEN; Mode of pathogenicity: None; Publications: 28543993, 20860806, 22344793, 11857550, 15148591, 19641926, 9279760; Phenotypes: Hydrocephalus with congenital idiopathic intestinal pseudoobstruction, OMIM:307000; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Paediatric pseudo-obstruction syndrome v0.54 KIF26A Achchuthan Shanmugasundram Publications for gene: KIF26A were set to
Paediatric pseudo-obstruction syndrome v0.53 KIF26A Achchuthan Shanmugasundram reviewed gene: KIF26A: Rating: RED; Mode of pathogenicity: None; Publications: 19914172, 33542431; Phenotypes: ; Mode of inheritance: None
Paediatric pseudo-obstruction syndrome v0.53 COX15 Arina Puzriakova Mode of inheritance for gene: COX15 was changed from to BIALLELIC, autosomal or pseudoautosomal
Undiagnosed metabolic disorders v1.571 COX15 Arina Puzriakova Phenotypes for gene: COX15 were changed from Complex IV (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors); Isolated complex IV deficiency; Leigh syndrome due to cytochrome c oxidase deficiency, 256000Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2, 615119; Mitochondrial Diseases; Mitochondrial Respiratory Chain Complex IV Deficiency to Mitochondrial complex IV deficiency, nuclear type 6, OMIM:615119
Childhood onset dystonia, chorea or related movement disorder v2.3 COX15 Arina Puzriakova Phenotypes for gene: COX15 were changed from Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2, 615119 to Mitochondrial complex IV deficiency, nuclear type 6, OMIM:615119
Intellectual disability v4.23 COX15 Arina Puzriakova Phenotypes for gene: COX15 were changed from Leigh syndrome due to cytochrome c oxidase deficiency, 256000Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2, 615119; MITOCHONDRIAL COMPLEX IV DEFICIENCY (MT-C4D) to Mitochondrial complex IV deficiency, nuclear type 6, OMIM:615119
Paediatric or syndromic cardiomyopathy v2.4 COX15 Arina Puzriakova Phenotypes for gene: COX15 were changed from Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2, 615119; Leigh syndrome due to cytochrome c oxidase deficiency, 256000 to Mitochondrial complex IV deficiency, nuclear type 6, OMIM:615119
Mitochondrial disorders v3.4 COX15 Arina Puzriakova Phenotypes for gene: COX15 were changed from Isolated complex IV deficiency; Leigh syndrome due to cytochrome c oxidase deficiency, 256000; Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2, 615119; Mitochondrial Diseases; Mitochondrial Respiratory Chain Complex IV Deficiency to Mitochondrial complex IV deficiency, nuclear type 6, OMIM:615119
Adult onset dystonia, chorea or related movement disorder v2.3 COX15 Arina Puzriakova Phenotypes for gene: COX15 were changed from Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2, 615119 to Mitochondrial complex IV deficiency, nuclear type 6, OMIM:615119
Early onset or syndromic epilepsy v3.14 COX15 Arina Puzriakova Phenotypes for gene: COX15 were changed from Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2 615119; Leigh syndrome 256000 to Mitochondrial complex IV deficiency, nuclear type 6, OMIM:615119
Likely inborn error of metabolism v3.4 COX15 Arina Puzriakova Phenotypes for gene: COX15 were changed from Mitochondrial Diseases; Mitochondrial Respiratory Chain Complex IV Deficiency; Isolated complex IV deficiency; Complex IV (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors); Leigh syndrome due to cytochrome c oxidase deficiency, 256000; Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2, 615119 to Mitochondrial complex IV deficiency, nuclear type 6, OMIM:615119
Possible mitochondrial disorder - nuclear genes v2.3 COX15 Arina Puzriakova Phenotypes for gene: COX15 were changed from Leigh syndrome due to cytochrome c oxidase deficiency, 256000; Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2, 615119 to Mitochondrial complex IV deficiency, nuclear type 6, OMIM:615119
Structural basal ganglia disorders v1.35 COX15 Arina Puzriakova Phenotypes for gene: COX15 were changed from to Mitochondrial complex IV deficiency, nuclear type 6, OMIM:615119
Mitochondrial disorder with complex IV deficiency v2.3 COX15 Arina Puzriakova Phenotypes for gene: COX15 were changed from Leigh syndrome due to cytochrome c oxidase deficiency, 256000; Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2, 615119 to Mitochondrial complex IV deficiency, nuclear type 6, OMIM:615119
Inherited white matter disorders v1.165 COX15 Arina Puzriakova Phenotypes for gene: COX15 were changed from Mitochondrial Leukoencephalopathy; Mitochondrial complex IV disorders to Mitochondrial complex IV deficiency, nuclear type 6, OMIM:615119; Mitochondrial Leukoencephalopathy
White matter disorders and cerebral calcification - narrow panel v2.5 COX15 Arina Puzriakova Phenotypes for gene: COX15 were changed from Mitochondrial complex IV disorders; Mitochondrial Leukoencephalopathy to Mitochondrial complex IV deficiency, nuclear type 6, OMIM:615119; Mitochondrial Leukoencephalopathy
Paediatric pseudo-obstruction syndrome v0.52 COX15 Arina Puzriakova Phenotypes for gene: COX15 were changed from to Mitochondrial complex IV deficiency, nuclear type 6, OMIM:615119
Likely inborn error of metabolism v3.3 COX10 Arina Puzriakova Phenotypes for gene: COX10 were changed from Encephalopathy, progressive mitochondrial, with proximal renal tubulopathy due to cytochrome coxidase deficiency; Mitochondrial Diseases; Mitochondrial Respiratory Chain Complex IV Deficiency; Isolated complex IV deficiency; Complex IV (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors) to Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046; Encephalopathy, progressive mitochondrial, with proximal renal tubulopathy due to cytochrome coxidase deficiency
Undiagnosed metabolic disorders v1.570 COX10 Arina Puzriakova Phenotypes for gene: COX10 were changed from Complex IV (Mitochondrial respiratory chain disorders (caused by nuclear variants only), OXPHOS assembly factors); Isolated complex IV deficiency; Encephalopathy, progressive mitochondrial, with proximal renal tubulopathy due to cytochrome coxidase deficiency; Mitochondrial Diseases; Mitochondrial Respiratory Chain Complex IV Deficiency to Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046; Encephalopathy, progressive mitochondrial, with proximal renal tubulopathy due to cytochrome coxidase deficiency
Childhood onset dystonia, chorea or related movement disorder v2.2 COX10 Arina Puzriakova Phenotypes for gene: COX10 were changed from Mitochondrial complex IV deficiency, 220110; Leigh syndrome due to mitochondrial COX4 deficiency, 256000 to Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046
Paediatric or syndromic cardiomyopathy v2.3 COX10 Arina Puzriakova Phenotypes for gene: COX10 were changed from Mitochondrial complex IV deficiency, 220110 to Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046
Adult onset dystonia, chorea or related movement disorder v2.2 COX10 Arina Puzriakova Phenotypes for gene: COX10 were changed from Leigh syndrome due to mitochondrial COX4 deficiency, 256000; Mitochondrial complex IV deficiency, 220110 to Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046
Mitochondrial disorders v3.3 COX10 Arina Puzriakova Phenotypes for gene: COX10 were changed from Isolated complex IV deficiency; Encephalopathy, progressive mitochondrial, with proximal renal tubulopathy due to cytochrome coxidase deficiency; Mitochondrial Diseases; Mitochondrial Respiratory Chain Complex IV Deficiency to Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046
Intellectual disability v4.22 COX10 Arina Puzriakova Phenotypes for gene: COX10 were changed from LEIGH SYNDROME (LS) to Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046
Early onset or syndromic epilepsy v3.13 COX10 Arina Puzriakova Phenotypes for gene: COX10 were changed from to Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046
Early onset or syndromic epilepsy v3.12 COX10 Arina Puzriakova Mode of inheritance for gene: COX10 was changed from to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v2.4 COX10 Arina Puzriakova Phenotypes for gene: COX10 were changed from MITOCHONDRIAL COMPLEX IV DEFICIENCY; LEIGH SYNDROME to Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046
Possible mitochondrial disorder - nuclear genes v2.2 COX10 Arina Puzriakova Phenotypes for gene: COX10 were changed from Mitochondrial complex IV deficiency, 220110 to Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046
Mitochondrial disorder with complex IV deficiency v2.2 COX10 Arina Puzriakova Phenotypes for gene: COX10 were changed from Mitochondrial complex IV deficiency, 220110 to Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046
Structural basal ganglia disorders v1.34 COX10 Arina Puzriakova Phenotypes for gene: COX10 were changed from to Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046
Unexplained young onset end-stage renal disease v2.4 COX10 Arina Puzriakova Phenotypes for gene: COX10 were changed from Encephalopathy, progressive mitochondrial, with proximal renal tubulopathy due tocytochrome c oxidase deficiency to Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046; Encephalopathy, progressive mitochondrial, with proximal renal tubulopathy due tocytochrome c oxidase deficiency
CAKUT v1.173 COX10 Arina Puzriakova Phenotypes for gene: COX10 were changed from Encephalopathy, progressive mitochondrial, with proximal renal tubulopathy due tocytochrome c oxidase deficiency to Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046; Encephalopathy, progressive mitochondrial, with proximal renal tubulopathy due tocytochrome c oxidase deficiency
Unexplained kidney failure in young people v1.117 COX10 Arina Puzriakova Phenotypes for gene: COX10 were changed from Encephalopathy, progressive mitochondrial, with proximal renal tubulopathy due tocytochrome c oxidase deficiency to Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046; Encephalopathy, progressive mitochondrial, with proximal renal tubulopathy due tocytochrome c oxidase deficiency
Inherited white matter disorders v1.164 COX10 Arina Puzriakova Phenotypes for gene: COX10 were changed from Mitochondrial complex IV disorder; Mitochondrial Leukoencephalopathy; General Leukodystrophy & Mitochondrial Leukoencephalopathy to Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046; General Leukodystrophy & Mitochondrial Leukoencephalopathy
Paediatric pseudo-obstruction syndrome v0.51 GFRA1 Achchuthan Shanmugasundram Phenotypes for gene: GFRA1 were changed from to Susceptibility to Hirschsprung disease, MONDO:0100179
Paediatric pseudo-obstruction syndrome v0.50 GFRA1 Achchuthan Shanmugasundram Publications for gene: GFRA1 were set to
White matter disorders and cerebral calcification - narrow panel v2.4 COX10 Arina Puzriakova Phenotypes for gene: COX10 were changed from General Leukodystrophy & Mitochondrial Leukoencephalopathy; Mitochondrial Leukoencephalopathy; Mitochondrial complex IV disorder to Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046; General Leukodystrophy & Mitochondrial Leukoencephalopathy
Paediatric pseudo-obstruction syndrome v0.49 GFRA1 Achchuthan Shanmugasundram Mode of inheritance for gene: GFRA1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Paediatric pseudo-obstruction syndrome v0.48 GFRA1 Achchuthan Shanmugasundram Classified gene: GFRA1 as Amber List (moderate evidence)
Paediatric pseudo-obstruction syndrome v0.48 GFRA1 Achchuthan Shanmugasundram Gene: gfra1 has been classified as Amber List (Moderate Evidence).
Paediatric pseudo-obstruction syndrome v0.47 GFRA1 Achchuthan Shanmugasundram Tag watchlist tag was added to gene: GFRA1.
Paediatric pseudo-obstruction syndrome v0.47 GFRA1 Achchuthan Shanmugasundram changed review comment from: Added watchlist tag as panel 63 to be notified of additional cases.; to: Added watchlist tag as in panel 63 to be notified of additional cases.
Paediatric pseudo-obstruction syndrome v0.47 GFRA1 Achchuthan Shanmugasundram changed review comment from: Comment on classification of this gene: Tis gene should be rated AMBER as curated in Familial Hirschsprung Disease panel (https://panelapp.genomicsengland.co.uk/panels/63/gene/GFRA1/). There is only limited literature evidence to support a causation role in Hirschsprung disease.

This gene is not associated with Susceptibility to Hirschsprung disease in OMIM yet.; to: Comment on classification of this gene: This gene should be rated AMBER as curated in Familial Hirschsprung Disease panel (https://panelapp.genomicsengland.co.uk/panels/63/gene/GFRA1/). There is only limited literature evidence to support a causation role in Hirschsprung disease.

This gene has not yet been associated with Susceptibility to Hirschsprung disease in OMIM.
Familial Hirschsprung Disease v1.9 GFRA1 Achchuthan Shanmugasundram Deleted their review
Paediatric pseudo-obstruction syndrome v0.47 GFRA1 Achchuthan Shanmugasundram commented on gene: GFRA1: Added watchlist tag as panel 63 to be notified of additional cases.
Paediatric pseudo-obstruction syndrome v0.47 COX10 Arina Puzriakova Classified gene: COX10 as Red List (low evidence)
Paediatric pseudo-obstruction syndrome v0.47 COX10 Arina Puzriakova Added comment: Comment on list classification: Could not find clear evidence linking this gene with intestinal pseudo-obstruction and therefore recommending Red gene rating at this time.
Paediatric pseudo-obstruction syndrome v0.47 COX10 Arina Puzriakova Gene: cox10 has been classified as Red List (Low Evidence).
Paediatric pseudo-obstruction syndrome v0.46 GFRA1 Achchuthan Shanmugasundram reviewed gene: GFRA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 28543993, 27370713, 9545641, 17507417, 12624147; Phenotypes: Susceptibility to Hirschsprung disease, MONDO:0100179; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Familial Hirschsprung Disease v1.9 GFRA1 Achchuthan Shanmugasundram commented on gene: GFRA1: Added watchlist tag as panel 63 to be notified of additional cases.
Familial Hirschsprung Disease v1.9 GFRA1 Achchuthan Shanmugasundram reviewed gene: GFRA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 28543993, 27370713, 9545641, 17507417, 12624147; Phenotypes: Susceptibility to Hirschsprung disease, MONDO:0100179; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Paediatric pseudo-obstruction syndrome v0.46 CHRNE Arina Puzriakova Publications for gene: CHRNE were set to
Paediatric pseudo-obstruction syndrome v0.45 C17orf107 Arina Puzriakova Publications for gene: C17orf107 were set to
Fetal anomalies v2.3 CHRNE Arina Puzriakova Phenotypes for gene: CHRNE were changed from Myasthenic syndrome, congenital, 4A, slow-channel, 605809; Myasthenic syndrome, congenital, 4B, fast-channel, 616324; Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency, 608931 to Myasthenic syndrome, congenital, 4A, slow-channel, OMIM:605809; Myasthenic syndrome, congenital, 4B, fast-channel, OMIM:616324; Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency, OMIM:608931
Arthrogryposis v4.3 CHRNE Arina Puzriakova Phenotypes for gene: CHRNE were changed from Myasthenic syndrome, congenital, 4A, slow-channel 605809; Myasthenic syndrome, congenital, 4B, fast-channel 616324; Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency 608931 to Myasthenic syndrome, congenital, 4A, slow-channel, OMIM:605809; Myasthenic syndrome, congenital, 4B, fast-channel, OMIM:616324; Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency, OMIM:608931
Paediatric pseudo-obstruction syndrome v0.44 C17orf107 Arina Puzriakova Phenotypes for gene: C17orf107 were changed from to Myasthenic syndrome, congenital, 4A, slow-channel, OMIM:605809; Myasthenic syndrome, congenital, 4B, fast-channel, OMIM:616324; Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency, OMIM:608931
Paediatric pseudo-obstruction syndrome v0.43 CHRNE Arina Puzriakova Phenotypes for gene: CHRNE were changed from to Myasthenic syndrome, congenital, 4A, slow-channel, OMIM:605809; Myasthenic syndrome, congenital, 4B, fast-channel, OMIM:616324; Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency, OMIM:608931
Paediatric pseudo-obstruction syndrome v0.42 CHRNE Arina Puzriakova Mode of inheritance for gene: CHRNE was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.41 CHRNE Arina Puzriakova Classified gene: CHRNE as Red List (low evidence)
Paediatric pseudo-obstruction syndrome v0.41 CHRNE Arina Puzriakova Added comment: Comment on list classification: C17orf107 [CHRNE] is associated with congenital myasthenic syndromes, however I could not find clear evidence of intestinal disturbance and therefore recommending a Red gene rating at this time.
Paediatric pseudo-obstruction syndrome v0.41 CHRNE Arina Puzriakova Gene: chrne has been classified as Red List (Low Evidence).
Paediatric pseudo-obstruction syndrome v0.40 C17orf107 Arina Puzriakova Classified gene: C17orf107 as Red List (low evidence)
Paediatric pseudo-obstruction syndrome v0.40 C17orf107 Arina Puzriakova Added comment: Comment on list classification: C17orf107 [CHRNE] is associated with congenital myasthenic syndromes, however I could not find clear evidence of intestinal disturbance and therefore recommending a Red gene rating at this time.
Paediatric pseudo-obstruction syndrome v0.40 C17orf107 Arina Puzriakova Gene: c17orf107 has been classified as Red List (Low Evidence).
Paediatric pseudo-obstruction syndrome v0.39 C17orf107 Arina Puzriakova Mode of inheritance for gene: C17orf107 was changed from to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.38 GDNF Achchuthan Shanmugasundram Phenotypes for gene: GDNF were changed from to {Hirschsprung disease, susceptibility to, 3}, OMIM:613711
Paediatric pseudo-obstruction syndrome v0.37 GDNF Achchuthan Shanmugasundram Mode of inheritance for gene: GDNF was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.36 GDNF Achchuthan Shanmugasundram reviewed gene: GDNF: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: {Hirschsprung disease, susceptibility to, 3}, OMIM:613711; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.36 FLNA Achchuthan Shanmugasundram changed review comment from: Comment on classification of this gene: The rating for this gene should be GREEN as this gene has been implicated in intestinal pseudo-obstruction, as identified from five unrelated families.

Four patients from family 1 reported with intestinal pseudo-obstruction in PMID:20871226 had diffuse abnormal layering of small intestinal smooth muscle (DAL). At least five males were affected in this family and they were all maternally-related. Both the mother and sister of patient 1 have normal intestinal motility and cranial magnetic resonance imaging, but the sister had a PDA and bifid uvula. Patient 5 from a second family was also reported with variant in FLNA gene (c.7021C>T; p.Gln2341Ter) and the parents also gave birth to a healthy female. Bot these cases suggest biallelic mode of inheritance in females.

2-bp deletion in exon 2 of the FLNA gene was found in the male proband and his second cousin and the variant was present in heterozygous state in the carrier females of the family (PMID:17357080). Similarly, a 4-bp deletion in exon 40 was identified in PMID:26059841, which results in translation of a mutant FLNA missing an internal region of 41 amino acids.

In another family, three males and four females were identified with a novel no-stop FLNA mutation (c.7941_7942delCT, p.(*2648Serext*100)). This variant causes classical X-linked periventricular nodular heterotopia (XL-PNH) in females and an unusual multi-organ phenotype in males (PMID:23873601).

This gene is associated to Intestinal pseudoobstruction, neuronal and Congenital short bowel syndrome in OMIM.; to: Comment on classification of this gene: The rating for this gene should be GREEN as this gene has been implicated in intestinal pseudo-obstruction, as identified from five unrelated families.

Four patients from family 1 reported with intestinal pseudo-obstruction in PMID:20871226 had diffuse abnormal layering of small intestinal smooth muscle (DAL). At least five males were affected in this family and they were all maternally-related. Both the mother and sister of patient 1 have normal intestinal motility and cranial magnetic resonance imaging, but the sister had a PDA and bifid uvula. Patient 5 from a second family was also reported with variant in FLNA gene (c.7021C>T; p.Gln2341Ter) and the parents also gave birth to a healthy female. Bot these cases suggest biallelic mode of inheritance in females.

2-bp deletion in exon 2 of the FLNA gene was found in the male proband and his second cousin and the variant was present in heterozygous state in the carrier females of the family (PMID:17357080). Similarly, a 4-bp deletion in exon 40 was identified in PMID:26059841, which results in translation of a mutant FLNA missing an internal region of 41 amino acids.

In another family, three males and four females were identified with a novel no-stop FLNA mutation (c.7941_7942delCT, p.(*2648Serext*100)). This variant causes classical X-linked periventricular nodular heterotopia (XL-PNH) in females and an unusual multi-organ phenotype in males (PMID:23873601).

This gene is associated with relevant phenotypes in both OMIM and Gene2Phenotype.
Paediatric pseudo-obstruction syndrome v0.36 FLNA Achchuthan Shanmugasundram changed review comment from: Comment on classification of this gene: The rating for this gene should be GREEN as this gene has been implicated in intestinal pseudo-obstruction, as identified from five unrelated families.

Four patients from family 1 reported with intestinal pseudo-obstruction in PMID:20871226 had diffuse abnormal layering of small intestinal smooth muscle (DAL). At least five males were affected in this family and they were all maternally-related. Both the mother and sister of patient 1 have normal intestinal motility and cranial magnetic resonance imaging, but the sister had a PDA and bifid uvula. Patient 5 from a second family was also reported with variant in FLNA gene (c.7021C>T; p.Gln2341Ter) and the parents also gave birth to a healthy female. Bot these cases suggest biallelic mode of inheritance in females.

2-bp deletion in exon 2 of the FLNA gene was found in the male proband and his second cousin and the variant was present in heterozygous state in the carrier females of the family (PMID:17357080). Similarly, a 4-bp deletion in exon 40 was identified in PMID:26059841, which results in translation of a mutant FLNA missing an internal region of 41 amino acids.

In another family, three males and four females were identified with a novel no-stop FLNA mutation (c.7941_7942delCT, p.(*2648Serext*100)). This variant causes classical X-linked periventricular nodular heterotopia (XL-PNH) in females and an unusual multi-organ phenotype in males (PMID:23873601).; to: Comment on classification of this gene: The rating for this gene should be GREEN as this gene has been implicated in intestinal pseudo-obstruction, as identified from five unrelated families.

Four patients from family 1 reported with intestinal pseudo-obstruction in PMID:20871226 had diffuse abnormal layering of small intestinal smooth muscle (DAL). At least five males were affected in this family and they were all maternally-related. Both the mother and sister of patient 1 have normal intestinal motility and cranial magnetic resonance imaging, but the sister had a PDA and bifid uvula. Patient 5 from a second family was also reported with variant in FLNA gene (c.7021C>T; p.Gln2341Ter) and the parents also gave birth to a healthy female. Bot these cases suggest biallelic mode of inheritance in females.

2-bp deletion in exon 2 of the FLNA gene was found in the male proband and his second cousin and the variant was present in heterozygous state in the carrier females of the family (PMID:17357080). Similarly, a 4-bp deletion in exon 40 was identified in PMID:26059841, which results in translation of a mutant FLNA missing an internal region of 41 amino acids.

In another family, three males and four females were identified with a novel no-stop FLNA mutation (c.7941_7942delCT, p.(*2648Serext*100)). This variant causes classical X-linked periventricular nodular heterotopia (XL-PNH) in females and an unusual multi-organ phenotype in males (PMID:23873601).

This gene is associated to Intestinal pseudoobstruction, neuronal and Congenital short bowel syndrome in OMIM.
Paediatric pseudo-obstruction syndrome v0.36 FOCAD Achchuthan Shanmugasundram Phenotypes for gene: FOCAD were changed from to Chronic intestinal pseudoobstruction, MONDO:0017574
Paediatric pseudo-obstruction syndrome v0.35 FOCAD Achchuthan Shanmugasundram Publications for gene: FOCAD were set to
Paediatric pseudo-obstruction syndrome v0.34 FOCAD Achchuthan Shanmugasundram reviewed gene: FOCAD: Rating: RED; Mode of pathogenicity: None; Publications: 31814461; Phenotypes: Chronic intestinal pseudoobstruction, MONDO:0017574; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.34 FLNA Achchuthan Shanmugasundram Phenotypes for gene: FLNA were changed from to Congenital short bowel syndrome, OMIM:300048; Intestinal pseudoobstruction, neuronal, OMIM:300048
Paediatric pseudo-obstruction syndrome v0.33 FLNA Achchuthan Shanmugasundram Publications for gene: FLNA were set to
Paediatric pseudo-obstruction syndrome v0.32 FLNA Achchuthan Shanmugasundram Mode of inheritance for gene: FLNA was changed from to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Paediatric pseudo-obstruction syndrome v0.31 FLNA Achchuthan Shanmugasundram Classified gene: FLNA as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.31 FLNA Achchuthan Shanmugasundram Gene: flna has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.30 FLNA Achchuthan Shanmugasundram reviewed gene: FLNA: Rating: GREEN; Mode of pathogenicity: None; Publications: 17357080, 20871226, 23873601, 26059841, 31848803, 33729000; Phenotypes: Congenital short bowel syndrome, OMIM:300048, Intestinal pseudoobstruction, neuronal, OMIM:300048; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Paediatric pseudo-obstruction syndrome v0.30 ERBB2 Achchuthan Shanmugasundram Publications for gene: ERBB2 were set to 33497358
Paediatric pseudo-obstruction syndrome v0.29 ERBB2 Achchuthan Shanmugasundram changed review comment from: Comment on classification of this gene: The rating for this gene should be RED, as the disease association was identified from only one family.

A Turkish female proband identified with biallelic variants (c.2129C>T/ p.Ala710Val) was reported with arthrogryposis, peripheral neuropathy, hearing loss and ptosis. Her brother with the same variant had similar clinical presentation with short-segment Hirschsprung disease (HSCR). In addition, histology revealed a lack of ganglion cells and a hyperplasia of nerve fibers in the colon resection specimen of the brother.

This gene-disease association is reported in OMIM, but not in Gene2Phenotype.; to: Comment on classification of this gene: The rating for this gene should be RED, as the disease association was identified from only one family.

A Turkish female proband identified with biallelic variants (c.2129C>T/ p.Ala710Val) was reported with arthrogryposis, peripheral neuropathy, hearing loss and ptosis. Her brother with the same variant had similar clinical presentation with short-segment Hirschsprung disease (HSCR). In addition, histology revealed a lack of ganglion cells and a hyperplasia of nerve fibers in the colon resection specimen of the brother.

This gene-disease association is reported in OMIM, but not in Gene2Phenotype.
Paediatric pseudo-obstruction syndrome v0.29 ERBB2 Achchuthan Shanmugasundram changed review comment from: Comment on classification of this gene: The rating for this gene should be RED, as the disease association was identified from only one family.

A Turkish female proband identified with biallelic variants (c.2129C>T/ p.Ala710Val) was reported with arthrogryposis, peripheral neuropathy, hearing loss and ptosis. Her brother with the same variant had similar clinical presentation with short-segment Hirschsprung disease (HSCR). In addition, histology revealed a lack of ganglion cells and a hyperplasia of nerve fibers in the colon resection specimen of the brother.; to: Comment on classification of this gene: The rating for this gene should be RED, as the disease association was identified from only one family.

A Turkish female proband identified with biallelic variants (c.2129C>T/ p.Ala710Val) was reported with arthrogryposis, peripheral neuropathy, hearing loss and ptosis. Her brother with the same variant had similar clinical presentation with short-segment Hirschsprung disease (HSCR). In addition, histology revealed a lack of ganglion cells and a hyperplasia of nerve fibers in the colon resection specimen of the brother.

This gene-disease association is reported in OMIM, but not in Gene2Phenotype.
Paediatric pseudo-obstruction syndrome v0.29 ERBB3 Achchuthan Shanmugasundram Publications for gene: ERBB3 were set to
Paediatric pseudo-obstruction syndrome v0.28 ERBB3 Achchuthan Shanmugasundram Phenotypes for gene: ERBB3 were changed from to Visceral neuropathy, familial, 1, autosomal recessive, OMIM:243180
Paediatric pseudo-obstruction syndrome v0.27 ERBB3 Achchuthan Shanmugasundram Mode of inheritance for gene: ERBB3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.26 ERBB3 Achchuthan Shanmugasundram Classified gene: ERBB3 as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.26 ERBB3 Achchuthan Shanmugasundram Gene: erbb3 has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.25 ERBB3 Achchuthan Shanmugasundram reviewed gene: ERBB3: Rating: GREEN; Mode of pathogenicity: None; Publications: 33497358; Phenotypes: Visceral neuropathy, familial, 1, autosomal recessive, OMIM:243180; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.25 COX10 Arina Puzriakova Mode of inheritance for gene: COX10 was changed from to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.24 COX10 Arina Puzriakova Phenotypes for gene: COX10 were changed from to Mitochondrial complex IV deficiency, nuclear type 3, OMIM:619046
Paediatric pseudo-obstruction syndrome v0.23 BCS1L Arina Puzriakova Classified gene: BCS1L as Red List (low evidence)
Paediatric pseudo-obstruction syndrome v0.23 BCS1L Arina Puzriakova Added comment: Comment on list classification: Could not find clear evidence linking this gene with intestinal pseudo-obstruction and therefore recommending Red gene rating at this time.
Paediatric pseudo-obstruction syndrome v0.23 BCS1L Arina Puzriakova Gene: bcs1l has been classified as Red List (Low Evidence).
Paediatric pseudo-obstruction syndrome v0.22 BCS1L Arina Puzriakova Mode of inheritance for gene: BCS1L was changed from to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.21 BCS1L Arina Puzriakova Phenotypes for gene: BCS1L were changed from to Mitochondrial complex III deficiency, nuclear type 1, OMIM:124000
Paediatric pseudo-obstruction syndrome v0.20 ERBB2 Achchuthan Shanmugasundram Publications for gene: ERBB2 were set to
Paediatric pseudo-obstruction syndrome v0.19 ERBB2 Achchuthan Shanmugasundram Phenotypes for gene: ERBB2 were changed from to Visceral neuropathy, familial, 2, autosomal recessive, OMIM:619465
Paediatric pseudo-obstruction syndrome v0.18 ERBB2 Achchuthan Shanmugasundram Mode of inheritance for gene: ERBB2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.17 ERBB2 Achchuthan Shanmugasundram reviewed gene: ERBB2: Rating: RED; Mode of pathogenicity: None; Publications: 33497358; Phenotypes: Visceral neuropathy, familial, 2, autosomal recessive, OMIM:619465; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.17 BCR Arina Puzriakova Classified gene: BCR as Red List (low evidence)
Paediatric pseudo-obstruction syndrome v0.17 BCR Arina Puzriakova Added comment: Comment on list classification: Not associated with any relevant phenotype in OMIM or G2P. Only a single patient has been reported in literature (PMID: 34190380) with paediatric intestinal pseudo-obstruction and a heterozygous de novo variant (c.3072+1G>A). Bcr null mice did display growth retardation and impaired gastrointestinal motility but additional patients required prior to adding as diagnostic-grade.
Paediatric pseudo-obstruction syndrome v0.17 BCR Arina Puzriakova Gene: bcr has been classified as Red List (Low Evidence).
Paediatric pseudo-obstruction syndrome v0.16 BCR Arina Puzriakova Phenotypes for gene: BCR were changed from to Paediatric intestinal pseudo-obstruction
Paediatric pseudo-obstruction syndrome v0.15 BCR Arina Puzriakova Mode of inheritance for gene: BCR was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.14 BCR Arina Puzriakova Publications for gene: BCR were set to
Paediatric pseudo-obstruction syndrome v0.13 ACTG2 Arina Puzriakova Publications for gene: ACTG2 were set to 24676022; 24337657; 33729000
Paediatric pseudo-obstruction syndrome v0.12 ACTG2 Arina Puzriakova Publications for gene: ACTG2 were set to 24676022; 24337657; 33729000; 31848803
Paediatric pseudo-obstruction syndrome v0.11 ACTG2 Arina Puzriakova Publications for gene: ACTG2 were set to
Paediatric pseudo-obstruction syndrome v0.10 ACTG2 Arina Puzriakova Classified gene: ACTG2 as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.10 ACTG2 Arina Puzriakova Gene: actg2 has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.9 ACTG2 Arina Puzriakova Mode of inheritance for gene: ACTG2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.8 ACTG2 Arina Puzriakova Phenotypes for gene: ACTG2 were changed from Megacystis-microcolon-intestinal hypoperistalsis syndrome 5, OMIM:619431 to Megacystis-microcolon-intestinal hypoperistalsis syndrome 5, OMIM:619431; Visceral myopathy 1, OMIM:155310
Paediatric pseudo-obstruction syndrome v0.7 ACTG2 Arina Puzriakova Phenotypes for gene: ACTG2 were changed from to Megacystis-microcolon-intestinal hypoperistalsis syndrome 5, OMIM:619431
Paediatric pseudo-obstruction syndrome v0.6 ACTA2 Arina Puzriakova Classified gene: ACTA2 as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.6 ACTA2 Arina Puzriakova Gene: acta2 has been classified as Green List (High Evidence).
Gastrointestinal neuromuscular disorders v1.23 ACTA2 Arina Puzriakova Phenotypes for gene: ACTA2 were changed from Multisystemic smooth muscle dysfunction syndrome, MIM# 613834 to Multisystemic smooth muscle dysfunction syndrome, OMIM:613834
Paediatric pseudo-obstruction syndrome v0.5 ACTA2 Arina Puzriakova Publications for gene: ACTA2 were set to
Gastrointestinal neuromuscular disorders v1.22 ACTA2 Arina Puzriakova Classified gene: ACTA2 as Green List (high evidence)
Gastrointestinal neuromuscular disorders v1.22 ACTA2 Arina Puzriakova Gene: acta2 has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.4 ACTA2 Arina Puzriakova commented on gene: ACTA2
Paediatric pseudo-obstruction syndrome v0.4 ACTA2 Arina Puzriakova Phenotypes for gene: ACTA2 were changed from to Multisystemic smooth muscle dysfunction syndrome, OMIM:613834
Paediatric pseudo-obstruction syndrome v0.3 ACTA2 Arina Puzriakova Mode of inheritance for gene: ACTA2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dilated and arrhythmogenic cardiomyopathy v2.2 SCN5A Arina Puzriakova Publications for gene: SCN5A were set to 20186049; 27532257
Paediatric or syndromic cardiomyopathy v2.2 SCN5A Arina Puzriakova Publications for gene: SCN5A were set to 24317018; doi:10. 1007/ s12265-016-9673-5
Retinal disorders v3.4 EYS Arina Puzriakova Phenotypes for gene: EYS were changed from Retinitis pigmentosa 25; Eye Disorders; Retinitis pigmentosa; Retinitis Pigmentosa, Recessive; Retinitis pigmentosa 25, 602772 to Retinitis pigmentosa 25, OMIM:602772
Retinal disorders v3.3 EYS Arina Puzriakova Publications for gene: EYS were set to
Paediatric pseudo-obstruction syndrome v0.2 ZEB2 Eleanor Williams reviewed gene: ZEB2: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Mowat-Wilson syndrome with a variable predisposition to HSCR; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 TYMP Eleanor Williams reviewed gene: TYMP: Rating: ; Mode of pathogenicity: ; Publications: 31848803; Phenotypes: Accumulation of thymidine in mitochondrial DNA leads to impaired function. Multi-system mitochondrial disease with progressive gastrointestinal dysmotility; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.2 TWNK Eleanor Williams reviewed gene: TWNK: Rating: ; Mode of pathogenicity: ; Publications: 23385875; Phenotypes: Feeding intolerance, irregular rhythm of respiration, hypoglycemia, lactic acidosis, liver cytolysis and neurological abnormalities.; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.2 TTC7A Eleanor Williams reviewed gene: TTC7A: Rating: ; Mode of pathogenicity: ; Publications: 31787977; Phenotypes: Lymphoproliferative syndrome and hypergammaglobulinemia and/or chronic intestinal pseudo-obstruction.; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 TPM3 Eleanor Williams reviewed gene: TPM3: Rating: ; Mode of pathogenicity: ; Publications: 30663199; Phenotypes: Megacolon; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 TK2 Eleanor Williams reviewed gene: TK2: Rating: ; Mode of pathogenicity: ; Publications: 23385875; Phenotypes: myopathic changes on EMG, Loss of motor function, progressive external ophthalmoplegia, respiratory failure; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.2 SURF1 Eleanor Williams reviewed gene: SURF1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Psychomotor regression, failure to thrive, hypotonia, dystonia, ataxia, peripheral neuropathy, ophthalmoparesis, nystagmus, optic atrophy; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 SUCLG1 Eleanor Williams reviewed gene: SUCLG1: Rating: ; Mode of pathogenicity: ; Publications: 23385875; Phenotypes: motor neuron changes on EMG, Decreased muscle tone, failure to thrive, microcephaly, GI dysmotility; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.2 SUCLA2 Eleanor Williams reviewed gene: SUCLA2: Rating: ; Mode of pathogenicity: ; Publications: 23385875; Phenotypes: motor neuron changes on EMG, Decreased muscle tone, failure to thrive, microcephaly, GI dysmotility; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.2 SOX10 Eleanor Williams reviewed gene: SOX10: Rating: ; Mode of pathogenicity: ; Publications: 29570554, 31848803; Phenotypes: Peripheral neuropathy with hypomyelination, sensorineural deafness and pseudo-obstruction; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.2 SGO1 Eleanor Williams reviewed gene: SGO1: Rating: ; Mode of pathogenicity: ; Publications: 31848803; Phenotypes: Accelerated cell cycle progression and enhanced activation of TGF-B signaling leading to changes in both the enteric nervous system and smooth muscle. ChronicAtrial andIntestinalDysrhythmia (CAID) syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.2 SEMA3F Eleanor Williams reviewed gene: SEMA3F: Rating: ; Mode of pathogenicity: ; Publications: 30663199; Phenotypes: Megacolon; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 SDHA Eleanor Williams reviewed gene: SDHA: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Psychomotor regression, failure to thrive, hypotonia, dystonia, ataxia, peripheral neuropathy, ophthalmoparesis, nystagmus, optic atrophy; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 SCN10A Eleanor Williams reviewed gene: SCN10A: Rating: ; Mode of pathogenicity: ; Publications: 30663199; Phenotypes: Colon sensory neurons activation; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 RRM2B Eleanor Williams reviewed gene: RRM2B: Rating: ; Mode of pathogenicity: ; Publications: 23385875; Phenotypes: Issues in maintenance of mtDNA dNTP pools; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 RET Eleanor Williams reviewed gene: RET: Rating: ; Mode of pathogenicity: ; Publications: 31848803; Phenotypes: Gain in function mutation associated with intestinal ganglioneuromas leading to increased cell number in the myenteric plexus and dysmotility; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.2 RAD21 Eleanor Williams reviewed gene: RAD21: Rating: ; Mode of pathogenicity: ; Publications: 31848803; Phenotypes: Pseudo-obstruction, megaduodenum, long segment Barretts esophagus and cardiac abnormalities; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.2 PROKR2 Eleanor Williams reviewed gene: PROKR2: Rating: ; Mode of pathogenicity: ; Publications: 21858136; Phenotypes: Long segment megacolon, HSCR; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.2 PROKR1 Eleanor Williams reviewed gene: PROKR1: Rating: ; Mode of pathogenicity: ; Publications: 21858136; Phenotypes: Long segment megacolon, HSCR; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.2 PROK1 Eleanor Williams reviewed gene: PROK1: Rating: ; Mode of pathogenicity: ; Publications: 21858136; Phenotypes: Long segment megacolon, HSCR; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.2 POLG Eleanor Williams reviewed gene: POLG: Rating: ; Mode of pathogenicity: ; Publications: 23385875, 31848803; Phenotypes: Associated with mitochondrial depletion and deletions. Severe hypotonia and generalized muscle weakness, severe abdominal distension and hypoactive bowel; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.2 PHOX2B Eleanor Williams reviewed gene: PHOX2B: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: monogenic syndrome with a variable predisposition to HSCR; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 PDCL3 Eleanor Williams reviewed gene: PDCL3: Rating: ; Mode of pathogenicity: ; Publications: 32621347; Phenotypes: Loss-of-function of this protein affects the contractility of smooth muscle tissues; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 NRTN Eleanor Williams reviewed gene: NRTN: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: 1 case reported.; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.2 NKX2-1 Eleanor Williams reviewed gene: NKX2-1: Rating: ; Mode of pathogenicity: ; Publications: 30663199; Phenotypes: Megacolon, oesophageal atresia; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 NDUFS1 Eleanor Williams reviewed gene: NDUFS1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Psychomotor regression, failure to thrive, hypotonia, dystonia, ataxia, peripheral neuropathy, ophthalmoparesis, nystagmus, optic atrophy; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 MYLK Eleanor Williams reviewed gene: MYLK: Rating: ; Mode of pathogenicity: ; Publications: 33729000, 31848803; Phenotypes: Abnormal MYLK leads to impaired smooth muscle cell contraction; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.2 MYL9 Eleanor Williams reviewed gene: MYL9: Rating: ; Mode of pathogenicity: ; Publications: 33729000, 31848803; Phenotypes: Abnormal MYL9 leads to impaired intestinal smooth muscle contractility; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.2 MYH11 Eleanor Williams reviewed gene: MYH11: Rating: ; Mode of pathogenicity: ; Publications: 33729000, 31848803; Phenotypes: Abnormal MYH11 in smooth muscle myosin leads to impaired contractility; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.2 MPV17 Eleanor Williams reviewed gene: MPV17: Rating: ; Mode of pathogenicity: ; Publications: 23385875; Phenotypes: Elevated transaminases, GGT, hyperbilirubinemia, failure to thrive; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.2 LMOD1 Eleanor Williams reviewed gene: LMOD1: Rating: ; Mode of pathogenicity: ; Publications: 33729000, 31848803; Phenotypes: Abnormal LMOD1 leads to impaired intestinal smooth muscle contractility; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.2 LIG3 Eleanor Williams reviewed gene: LIG3: Rating: ; Mode of pathogenicity: ; Publications: 33855352; Phenotypes: ; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 L1CAM Eleanor Williams reviewed gene: L1CAM: Rating: ; Mode of pathogenicity: ; Publications: 31848803; Phenotypes: Defect in the differentiation of the interstitial cells of Cajal leading to progressive distension and intermittent episodes of obstruction; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.2 KIF26A Eleanor Williams reviewed gene: KIF26A: Rating: ; Mode of pathogenicity: ; Publications: 30663199; Phenotypes: GDNF-Ret in ENS development; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 GFRA1 Eleanor Williams reviewed gene: GFRA1: Rating: ; Mode of pathogenicity: ; Publications: 30663199; Phenotypes: Effect on ENS development; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 GDNF Eleanor Williams reviewed gene: GDNF: Rating: ; Mode of pathogenicity: ; Publications: 21858136; Phenotypes: Long segment megacolon, HSCR; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.2 FOCAD Eleanor Williams reviewed gene: FOCAD: Rating: ; Mode of pathogenicity: ; Publications: 31814461; Phenotypes: familial intestinal degenerative neuropathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.2 FLNA Eleanor Williams reviewed gene: FLNA: Rating: ; Mode of pathogenicity: ; Publications: 33729000, 31848803; Phenotypes: Cytoskeletal abnormalities and potentially disrupts enteric-neuron structure and function. Seizures and progressive abdominal distension and obstruction; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Paediatric pseudo-obstruction syndrome v0.2 ERBB3 Eleanor Williams reviewed gene: ERBB3: Rating: ; Mode of pathogenicity: ; Publications: 33720042; Phenotypes: Aganglionosis, hypoganglionosis, and intestinal smooth muscle abnormalities; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 ERBB2 Eleanor Williams reviewed gene: ERBB2: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 EDNRB Eleanor Williams reviewed gene: EDNRB: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: monogenic syndrome with a variable predisposition to HSCR; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 EDN3 Eleanor Williams reviewed gene: EDN3: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: monogenic syndrome with a variable predisposition to HSCR; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 ECE1 Eleanor Williams reviewed gene: ECE1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Short segment megacolon, craniofacial defects; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.2 DLX2 Eleanor Williams reviewed gene: DLX2: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: massive proximal bowel distention attributed to abnormal motility; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 DLX1 Eleanor Williams reviewed gene: DLX1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: massive proximal bowel distention attributed to abnormal motility; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 DGUOK Eleanor Williams reviewed gene: DGUOK: Rating: ; Mode of pathogenicity: ; Publications: 23385875; Phenotypes: Elevated serum concentration of tyrosine/phenylalanine, elevation of liver enzymes, increased serum concentration of ferritin, deficiency in complexes I, III, IV; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.2 DDX3X Eleanor Williams reviewed gene: DDX3X: Rating: ; Mode of pathogenicity: ; Publications: 32896648; Phenotypes: Psychomotor retardation, severe constipation, and a recurrent paralytic ileus.; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 COX15 Eleanor Williams reviewed gene: COX15: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Psychomotor regression, failure to thrive, hypotonia, dystonia, ataxia, peripheral neuropathy, ophthalmoparesis, nystagmus, optic atrophy; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 COX10 Eleanor Williams reviewed gene: COX10: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Psychomotor regression, failure to thrive, hypotonia, dystonia, ataxia, peripheral neuropathy, ophthalmoparesis, nystagmus, optic atrophy; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 CHRNE Eleanor Williams reviewed gene: CHRNE: Rating: ; Mode of pathogenicity: ; Publications: 30663199; Phenotypes: Congenital myasthenia, cholinergic receptors; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 C17orf107 Eleanor Williams reviewed gene: C17orf107: Rating: ; Mode of pathogenicity: ; Publications: 30663199; Phenotypes: Congenital myasthenia, cholinergic receptors; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 BCS1L Eleanor Williams reviewed gene: BCS1L: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: Psychomotor regression, failure to thrive, hypotonia, dystonia, ataxia, peripheral neuropathy, ophthalmoparesis, nystagmus, optic atrophy; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 BCR Eleanor Williams reviewed gene: BCR: Rating: ; Mode of pathogenicity: ; Publications: 34190380; Phenotypes: Growth retardation and impaired gastrointestinal motility; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 ACTG2 Eleanor Williams reviewed gene: ACTG2: Rating: ; Mode of pathogenicity: ; Publications: 33729000, 31848803; Phenotypes: Altered ACTG2 protein in the muscularis propria leads to impaired contractility; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.2 ACTA2 Eleanor Williams reviewed gene: ACTA2: Rating: ; Mode of pathogenicity: ; Publications: 33729000; Phenotypes: Dysfunction of SMCs throughout the body, leading to aortic and cerebrovascular disease, fixed dilated pupils, hypotonic bladder, malrotation, and hypoperistalsis of the gut and pulmonary hypertension.; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.1 ZEB2 Eleanor Williams gene: ZEB2 was added
gene: ZEB2 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: ZEB2 was set to
Paediatric pseudo-obstruction syndrome v0.1 TYMP Eleanor Williams gene: TYMP was added
gene: TYMP was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: TYMP was set to
Paediatric pseudo-obstruction syndrome v0.1 TWNK Eleanor Williams gene: TWNK was added
gene: TWNK was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: TWNK was set to
Paediatric pseudo-obstruction syndrome v0.1 TTC7A Eleanor Williams gene: TTC7A was added
gene: TTC7A was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: TTC7A was set to
Paediatric pseudo-obstruction syndrome v0.1 TPM3 Eleanor Williams gene: TPM3 was added
gene: TPM3 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: TPM3 was set to
Paediatric pseudo-obstruction syndrome v0.1 TK2 Eleanor Williams gene: TK2 was added
gene: TK2 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: TK2 was set to
Paediatric pseudo-obstruction syndrome v0.1 SURF1 Eleanor Williams gene: SURF1 was added
gene: SURF1 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: SURF1 was set to
Paediatric pseudo-obstruction syndrome v0.1 SUCLG1 Eleanor Williams gene: SUCLG1 was added
gene: SUCLG1 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: SUCLG1 was set to
Paediatric pseudo-obstruction syndrome v0.1 SUCLA2 Eleanor Williams gene: SUCLA2 was added
gene: SUCLA2 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: SUCLA2 was set to
Paediatric pseudo-obstruction syndrome v0.1 SOX10 Eleanor Williams gene: SOX10 was added
gene: SOX10 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: SOX10 was set to
Paediatric pseudo-obstruction syndrome v0.1 SGO1 Eleanor Williams gene: SGO1 was added
gene: SGO1 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: SGO1 was set to
Paediatric pseudo-obstruction syndrome v0.1 SEMA3F Eleanor Williams gene: SEMA3F was added
gene: SEMA3F was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: SEMA3F was set to
Paediatric pseudo-obstruction syndrome v0.1 SDHA Eleanor Williams gene: SDHA was added
gene: SDHA was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: SDHA was set to
Paediatric pseudo-obstruction syndrome v0.1 SCN10A Eleanor Williams gene: SCN10A was added
gene: SCN10A was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: SCN10A was set to
Paediatric pseudo-obstruction syndrome v0.1 RRM2B Eleanor Williams gene: RRM2B was added
gene: RRM2B was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: RRM2B was set to
Paediatric pseudo-obstruction syndrome v0.1 RET Eleanor Williams gene: RET was added
gene: RET was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: RET was set to
Paediatric pseudo-obstruction syndrome v0.1 RAD21 Eleanor Williams gene: RAD21 was added
gene: RAD21 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: RAD21 was set to
Paediatric pseudo-obstruction syndrome v0.1 PROKR2 Eleanor Williams gene: PROKR2 was added
gene: PROKR2 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: PROKR2 was set to
Paediatric pseudo-obstruction syndrome v0.1 PROKR1 Eleanor Williams gene: PROKR1 was added
gene: PROKR1 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: PROKR1 was set to
Paediatric pseudo-obstruction syndrome v0.1 PROK1 Eleanor Williams gene: PROK1 was added
gene: PROK1 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: PROK1 was set to
Paediatric pseudo-obstruction syndrome v0.1 POLG Eleanor Williams gene: POLG was added
gene: POLG was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: POLG was set to
Paediatric pseudo-obstruction syndrome v0.1 PHOX2B Eleanor Williams gene: PHOX2B was added
gene: PHOX2B was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: PHOX2B was set to
Paediatric pseudo-obstruction syndrome v0.1 PDCL3 Eleanor Williams gene: PDCL3 was added
gene: PDCL3 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: PDCL3 was set to
Paediatric pseudo-obstruction syndrome v0.1 NRTN Eleanor Williams gene: NRTN was added
gene: NRTN was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: NRTN was set to
Paediatric pseudo-obstruction syndrome v0.1 NKX2-1 Eleanor Williams gene: NKX2-1 was added
gene: NKX2-1 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: NKX2-1 was set to
Paediatric pseudo-obstruction syndrome v0.1 NDUFS1 Eleanor Williams gene: NDUFS1 was added
gene: NDUFS1 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: NDUFS1 was set to
Paediatric pseudo-obstruction syndrome v0.1 MYLK Eleanor Williams gene: MYLK was added
gene: MYLK was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: MYLK was set to
Paediatric pseudo-obstruction syndrome v0.1 MYL9 Eleanor Williams gene: MYL9 was added
gene: MYL9 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: MYL9 was set to
Paediatric pseudo-obstruction syndrome v0.1 MYH11 Eleanor Williams gene: MYH11 was added
gene: MYH11 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: MYH11 was set to
Paediatric pseudo-obstruction syndrome v0.1 MPV17 Eleanor Williams gene: MPV17 was added
gene: MPV17 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: MPV17 was set to
Paediatric pseudo-obstruction syndrome v0.1 LMOD1 Eleanor Williams gene: LMOD1 was added
gene: LMOD1 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: LMOD1 was set to
Paediatric pseudo-obstruction syndrome v0.1 LIG3 Eleanor Williams gene: LIG3 was added
gene: LIG3 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: LIG3 was set to
Paediatric pseudo-obstruction syndrome v0.1 L1CAM Eleanor Williams gene: L1CAM was added
gene: L1CAM was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: L1CAM was set to
Paediatric pseudo-obstruction syndrome v0.1 KIF26A Eleanor Williams gene: KIF26A was added
gene: KIF26A was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: KIF26A was set to
Paediatric pseudo-obstruction syndrome v0.1 GFRA1 Eleanor Williams gene: GFRA1 was added
gene: GFRA1 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: GFRA1 was set to
Paediatric pseudo-obstruction syndrome v0.1 GDNF Eleanor Williams gene: GDNF was added
gene: GDNF was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: GDNF was set to
Paediatric pseudo-obstruction syndrome v0.1 FOCAD Eleanor Williams gene: FOCAD was added
gene: FOCAD was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: FOCAD was set to
Paediatric pseudo-obstruction syndrome v0.1 FLNA Eleanor Williams gene: FLNA was added
gene: FLNA was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: FLNA was set to
Paediatric pseudo-obstruction syndrome v0.1 ERBB3 Eleanor Williams gene: ERBB3 was added
gene: ERBB3 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: ERBB3 was set to
Paediatric pseudo-obstruction syndrome v0.1 ERBB2 Eleanor Williams gene: ERBB2 was added
gene: ERBB2 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: ERBB2 was set to
Paediatric pseudo-obstruction syndrome v0.1 EDNRB Eleanor Williams gene: EDNRB was added
gene: EDNRB was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: EDNRB was set to
Paediatric pseudo-obstruction syndrome v0.1 EDN3 Eleanor Williams gene: EDN3 was added
gene: EDN3 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: EDN3 was set to
Paediatric pseudo-obstruction syndrome v0.1 ECE1 Eleanor Williams gene: ECE1 was added
gene: ECE1 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: ECE1 was set to
Paediatric pseudo-obstruction syndrome v0.1 DLX2 Eleanor Williams gene: DLX2 was added
gene: DLX2 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: DLX2 was set to
Paediatric pseudo-obstruction syndrome v0.1 DLX1 Eleanor Williams gene: DLX1 was added
gene: DLX1 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: DLX1 was set to
Paediatric pseudo-obstruction syndrome v0.1 DGUOK Eleanor Williams gene: DGUOK was added
gene: DGUOK was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: DGUOK was set to
Paediatric pseudo-obstruction syndrome v0.1 DDX3X Eleanor Williams gene: DDX3X was added
gene: DDX3X was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: DDX3X was set to
Paediatric pseudo-obstruction syndrome v0.1 COX15 Eleanor Williams gene: COX15 was added
gene: COX15 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: COX15 was set to
Paediatric pseudo-obstruction syndrome v0.1 COX10 Eleanor Williams gene: COX10 was added
gene: COX10 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: COX10 was set to
Paediatric pseudo-obstruction syndrome v0.1 CHRNE Eleanor Williams gene: CHRNE was added
gene: CHRNE was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: CHRNE was set to
Paediatric pseudo-obstruction syndrome v0.1 C17orf107 Eleanor Williams gene: C17orf107 was added
gene: C17orf107 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: C17orf107 was set to
Paediatric pseudo-obstruction syndrome v0.1 BCS1L Eleanor Williams gene: BCS1L was added
gene: BCS1L was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: BCS1L was set to
Paediatric pseudo-obstruction syndrome v0.1 BCR Eleanor Williams gene: BCR was added
gene: BCR was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: BCR was set to
Paediatric pseudo-obstruction syndrome v0.1 ACTG2 Eleanor Williams gene: ACTG2 was added
gene: ACTG2 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: ACTG2 was set to
Paediatric pseudo-obstruction syndrome v0.1 ACTA2 Eleanor Williams gene: ACTA2 was added
gene: ACTA2 was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: ACTA2 was set to
Paediatric pseudo-obstruction syndrome v0.0 Eleanor Williams Added Panel Paediatric pseudo-obstruction syndrome
Congenital myopathy v3.11 FXR1 Arina Puzriakova Publications for gene: FXR1 were set to 30770808
Intellectual disability v4.21 SOX4 Arina Puzriakova Phenotypes for gene: SOX4 were changed from Coffin-Siris syndrome 10, 618506; Syndromic intellectual disability; Global developmental delay; Intellectual disability; Growth delay; Clinodactyly of the 5th finger; facial dysmorphism to Coffin-Siris syndrome 10, OMIM:618506; Syndromic intellectual disability; Global developmental delay; Intellectual disability; Growth delay; Clinodactyly of the 5th finger; facial dysmorphism
Intellectual disability v4.20 SOX4 Arina Puzriakova Publications for gene: SOX4 were set to 30661772
Nephrocalcinosis or nephrolithiasis v3.2 SLC26A6 Arina Puzriakova gene: SLC26A6 was added
gene: SLC26A6 was added to Nephrocalcinosis or nephrolithiasis. Sources: Literature
watchlist tags were added to gene: SLC26A6.
Mode of inheritance for gene: SLC26A6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SLC26A6 were set to 35115415
Phenotypes for gene: SLC26A6 were set to Enteric hyperoxaluria and nephrolithiasis
Added comment: Cornière et al. 2022 (PMID: 35115415) identified a single family with a heterozygous missense VUS (c.1519C>T/p.R507W) in the SLC26A6 gene. However, the variant was found in 5 out of 280 674 alleles reported in gnomAD (Europeans and South Asians). In vitro studies showed that the variant affects both SLC26A6 transport activity and membrane surface expression, in turn reducing Cl− dependant oxalate transport. Cotransfection studies indicated a dominant-negative effect on WT. Slc26a6 null mice similarly displayed hyperoxalemia and hyperoxaluria which were caused by defective intestinal back-secretion of dietary oxalate (PMID: 21170874; 32660969)

SLC26A6 is currently not associated with any human phenotype in OMIM or G2P.
Sources: Literature
Likely inborn error of metabolism v3.2 SLC26A6 Arina Puzriakova gene: SLC26A6 was added
gene: SLC26A6 was added to Inborn errors of metabolism. Sources: Literature
watchlist tags were added to gene: SLC26A6.
Mode of inheritance for gene: SLC26A6 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SLC26A6 were set to 35115415
Phenotypes for gene: SLC26A6 were set to Enteric hyperoxaluria and nephrolithiasis
Added comment: Cornière et al. 2022 (PMID: 35115415) identified a single family with a heterozygous missense VUS (c.1519C>T/p.R507W) in the SLC26A6 gene. However, the variant was found in 5 out of 280 674 alleles reported in gnomAD (Europeans and South Asians). In vitro studies showed that the variant affects both SLC26A6 transport activity and membrane surface expression, in turn reducing Cl− dependant oxalate transport. Cotransfection studies indicated a dominant-negative effect on WT. Slc26a6 null mice similarly displayed hyperoxalemia and hyperoxaluria which were caused by defective intestinal back-secretion of dietary oxalate (PMID: 21170874; 32660969)

SLC26A6 is currently not associated with any human phenotype in OMIM or G2P.
Sources: Literature
Intellectual disability v4.19 CASK Arina Puzriakova Publications for gene: CASK were set to
Cerebellar hypoplasia v1.71 CASK Arina Puzriakova Publications for gene: CASK were set to
Severe microcephaly v3.3 CASK Arina Puzriakova Publications for gene: CASK were set to
Ataxia and cerebellar anomalies - narrow panel v3.20 CASK Arina Puzriakova Publications for gene: CASK were set to 35149592
Malformations of cortical development v3.3 CASK Arina Puzriakova Publications for gene: CASK were set to 21954287; 20595373; 32700313; 33090494; 33272775
Ataxia and cerebellar anomalies - narrow panel v3.19 CASK Arina Puzriakova Publications for gene: CASK were set to
Intellectual disability v4.18 KLHL20 Arina Puzriakova Tag Q4_22_promote_green tag was added to gene: KLHL20.
Early onset or syndromic epilepsy v3.11 KLHL20 Arina Puzriakova Classified gene: KLHL20 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v3.11 KLHL20 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel review.
-----
Sleyp et al. 2022 (PMID: 36214804) reported on 14 patients with de novo missense variants who all presented with mild to severe ID, seizures, ASD, hyperactivity, and dysmorphic facial features. One variant (c.1069G>A, p.Gly357Arg) was recurrent in 11/14 cases but all variants clustered in the Kelch-type β-propeller domain (substrate binding surface) of the KLHL20 protein. No functional studies were performed but given the overlap in clinical presentation observed in patients with the same recurrent variant but also multiple different variants, its worth including as diagnostic-grade.
Early onset or syndromic epilepsy v3.11 KLHL20 Arina Puzriakova Gene: klhl20 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.18 KLHL20 Arina Puzriakova Classified gene: KLHL20 as Amber List (moderate evidence)
Intellectual disability v4.18 KLHL20 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel review.
-----
Sleyp et al. 2022 (PMID: 36214804) reported on 14 patients with de novo missense variants who all presented with mild to severe ID, seizures, ASD, hyperactivity, and dysmorphic facial features. One variant (c.1069G>A, p.Gly357Arg) was recurrent in 11/14 cases but all variants clustered in the Kelch-type β-propeller domain (substrate binding surface) of the KLHL20 protein. No functional studies were performed but given the overlap in clinical presentation observed in patients with the same recurrent variant but also multiple different variants, its worth including as diagnostic-grade.
Intellectual disability v4.18 KLHL20 Arina Puzriakova Gene: klhl20 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v3.10 KLHL20 Arina Puzriakova Tag Q4_22_promote_green tag was added to gene: KLHL20.
Infantile enterocolitis & monogenic inflammatory bowel disease v1.39 TGFBR2 Dmitrijs Rots reviewed gene: TGFBR2: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Arthrogryposis v4.2 KCNK3 Arina Puzriakova changed review comment from: Comment on list classification: Given the number of unrelated cases with a comparable phenotype, all shown to have variants that cluster near the X-gate and cause increased channel activation, this gene should be promoted to Green status at the next GMS panel update.

The overall phenotype is likely most compatible with the Paediatric disorders super panel, and addition to the ID panel will ensure this genes' inclusion.; to: Comment on list classification: Given the number of unrelated cases with a comparable phenotype (including arthrogryposis/flexion contractures/foot deformities), all shown to have variants that cluster near the X-gate and cause increased channel activation, this gene should be promoted to Green status at the next GMS panel update.
Arthrogryposis v4.2 KCNK3 Arina Puzriakova Entity copied from Intellectual disability v4.17
Arthrogryposis v4.2 KCNK3 Arina Puzriakova gene: KCNK3 was added
gene: KCNK3 was added to Arthrogryposis. Sources: Literature,Expert Review Amber
Q4_22_promote_green tags were added to gene: KCNK3.
Mode of inheritance for gene: KCNK3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KCNK3 were set to 36195757
Phenotypes for gene: KCNK3 were set to Developmental disorder with sleep apnea
Mode of pathogenicity for gene: KCNK3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v4.17 KCNK3 Arina Puzriakova Classified gene: KCNK3 as Amber List (moderate evidence)
Intellectual disability v4.17 KCNK3 Arina Puzriakova Added comment: Comment on list classification: Given the number of unrelated cases with a comparable phenotype, all shown to have variants that cluster near the X-gate and cause increased channel activation, this gene should be promoted to Green status at the next GMS panel update.

The overall phenotype is likely most compatible with the Paediatric disorders super panel, and addition to the ID panel will ensure this genes' inclusion.
Intellectual disability v4.17 KCNK3 Arina Puzriakova Gene: kcnk3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.16 KCNK3 Arina Puzriakova gene: KCNK3 was added
gene: KCNK3 was added to Intellectual disability. Sources: Literature
Q4_22_promote_green tags were added to gene: KCNK3.
Mode of inheritance for gene: KCNK3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: KCNK3 were set to 36195757
Phenotypes for gene: KCNK3 were set to Developmental disorder with sleep apnea
Mode of pathogenicity for gene: KCNK3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Added comment: Heterozygous variant in the KCNK3 gene already have a well-established link with pulmonary arterial hypertension (OMIM:615344).

However, Sormann et al. 2022 (PMID: 36195757) identified nine unrelated individuals harbouring one of six de novo missense variants in KCNK3 who presented with developmental delay and sleep apnea among other variable features (musculoskeletal and limb anomalies, abnormalities of male genitalia/groin and digestive disturbance). The variants were shown to cause defective X-gating leading to overactive channels that no longer respond to inhibition by G-protein-coupled receptor pathways (i.e. GOF), distinct from the PAH mechanism which is caused by LOF variants.
Sources: Literature
Pulmonary arterial hypertension v3.2 KCNK3 Arina Puzriakova Phenotypes for gene: KCNK3 were changed from Idiopathic pulmonary arterial hypertension; IPAH; Heritable pulmonary arterial hypertension; HPAH; Pulmonary arterial hypertension; Pulmonary hypertension, primary, 4, 615344 to Pulmonary hypertension, primary, 4, OMIM:615344
Congenital muscular dystrophy v3.17 POGLUT1 Sarah Leigh Tag watchlist was removed from gene: POGLUT1.
Tag Q4_22_promote_green tag was added to gene: POGLUT1.
Congenital muscular dystrophy v3.17 POGLUT1 Sarah Leigh edited their review of gene: POGLUT1: Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. PMID: 31897643 reports seven POGLUT1 variants in six families with Muscular dystrophy, limb-girdle, autosomal recessive 21, OMIM:617232. Supportive in vitro and in vivo functional studies were presented in PMID: 31897643.; Changed rating: GREEN
Congenital muscular dystrophy v3.17 POGLUT1 Sarah Leigh Publications for gene: POGLUT1 were set to 27807076; 33861953
Congenital muscular dystrophy v3.16 POGLUT1 Sarah Leigh Phenotypes for gene: POGLUT1 were changed from ?Muscular dystrophy, limb-girdle, autosomal recessive 21, 617232 to Muscular dystrophy, limb-girdle, autosomal recessive 21, OMIM:617232; autosomal recessive limb-girdle muscular dystrophy type 2R1, MONDO:0014977
Congenital muscular dystrophy v3.15 POGLUT1 Sarah Leigh Classified gene: POGLUT1 as Amber List (moderate evidence)
Congenital muscular dystrophy v3.15 POGLUT1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Congenital muscular dystrophy v3.15 POGLUT1 Sarah Leigh Gene: poglut1 has been classified as Amber List (Moderate Evidence).
Congenital muscular dystrophy v3.14 POGLUT1 Sarah Leigh Publications for gene: POGLUT1 were set to 27807076
Congenital muscular dystrophy v3.13 GGPS1 Sarah Leigh Publications for gene: GGPS1 were set to 32403198
Early onset or syndromic epilepsy v3.10 DNM1 Sarah Leigh Publications for gene: DNM1 were set to 25262651; 27066543; 33372033; 34172529
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.3 DPM3 Sarah Leigh Tag Q4_22_promote_green tag was added to gene: DPM3.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.3 DPM3 Sarah Leigh edited their review of gene: DPM3: Added comment: Associated with relevant phenotype in OMIM and as strong Gen2Phen gene. At least four variants have been reported in at least five cases, together with supportive functional studies (PMID: 19576565; 31469168).; Changed rating: GREEN
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.3 DPM3 Sarah Leigh Classified gene: DPM3 as Amber List (moderate evidence)
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.3 DPM3 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.3 DPM3 Sarah Leigh Gene: dpm3 has been classified as Amber List (Moderate Evidence).
Congenital muscular dystrophy v3.12 HNRNPA2B1 Sarah Leigh Tag Q4_22_promote_green tag was added to gene: HNRNPA2B1.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.2 DPM3 Sarah Leigh Publications for gene: DPM3 were set to 28803818; 19576565
Congenital muscular dystrophy v3.12 DPM3 Sarah Leigh Publications for gene: DPM3 were set to 19576565
Congenital muscular dystrophy v3.11 HNRNPA2B1 Sarah Leigh Classified gene: HNRNPA2B1 as Amber List (moderate evidence)
Congenital muscular dystrophy v3.11 HNRNPA2B1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Congenital muscular dystrophy v3.11 HNRNPA2B1 Sarah Leigh Gene: hnrnpa2b1 has been classified as Amber List (Moderate Evidence).
Congenital muscular dystrophy v3.10 HNRNPA2B1 Sarah Leigh Added comment: Comment on phenotypes: The OMIM phenotype for HNRNPA2B1 (?Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2, OMIM:615422) is based on one family. PMID: 35484142 presents further variants associated with an expanded phenotype.
Congenital muscular dystrophy v3.10 HNRNPA2B1 Sarah Leigh Phenotypes for gene: HNRNPA2B1 were changed from ?Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2, OMIM:615422; inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2, MONDO:0014178 to early-onset oculopharyngeal muscular dystrophy, muscular dystrophy, congenital myopathy
Congenital muscular dystrophy v3.9 HNRNPA2B1 Sarah Leigh edited their review of gene: HNRNPA2B1: Added comment: PMID: 35484142 reports nine heterozygous terminating HNRNPA2B1 variants in ten unrelated cases of early onset severe, progressive muscular dystrophy, reminiscent of oculopharyngeal muscular dystrophy (OPMD); Changed rating: GREEN; Changed publications to: 35484142; Changed phenotypes to: early-onset oculopharyngeal muscular dystrophy
Intellectual disability v4.15 RPL10 Dmitrijs Rots reviewed gene: RPL10: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 35876338; Phenotypes: ID, dysmorphic features, progressive postnatal microcephaly, and retinal anomalies; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ataxia and cerebellar anomalies - narrow panel v3.18 SPTAN1 Dmitrijs Rots gene: SPTAN1 was added
gene: SPTAN1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: SPTAN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPTAN1 were set to 36331550; 35150594
Phenotypes for gene: SPTAN1 were set to Ataxia; hereditary spastic paraplegia
Review for gene: SPTAN1 was set to GREEN
Added comment: Two large cohorts (36331550; 35150594) described >30 cases with hereditary ataxia and a variant in SPTAN1.
Sources: Literature
Early onset or syndromic epilepsy v3.9 FRMD5 Arina Puzriakova Classified gene: FRMD5 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v3.9 FRMD5 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update - at least 5 unrelated cases with seizures plus supportive fly model.
Early onset or syndromic epilepsy v3.9 FRMD5 Arina Puzriakova Gene: frmd5 has been classified as Amber List (Moderate Evidence).
Hereditary ataxia with onset in adulthood v3.5 ATP2B3 Dmitrijs Rots reviewed gene: ATP2B3: Rating: ; Mode of pathogenicity: None; Publications: 36207321, 28807751, 25953895; Phenotypes: Ataxia; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Ataxia and cerebellar anomalies - narrow panel v3.18 FRMD5 Arina Puzriakova Classified gene: FRMD5 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v3.18 FRMD5 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update - at least 7 unrelated cases with ataxia plus supportive fly model.
Ataxia and cerebellar anomalies - narrow panel v3.18 FRMD5 Arina Puzriakova Gene: frmd5 has been classified as Amber List (Moderate Evidence).
Intellectual disability v4.15 FRMD5 Arina Puzriakova Classified gene: FRMD5 as Amber List (moderate evidence)
Intellectual disability v4.15 FRMD5 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update - at least 8 unrelated cases plus supportive fly model.
Intellectual disability v4.15 FRMD5 Arina Puzriakova Gene: frmd5 has been classified as Amber List (Moderate Evidence).
Congenital muscular dystrophy v3.9 HNRNPA2B1 Sarah Leigh Phenotypes for gene: HNRNPA2B1 were changed from oculopharyngodistal myopathy, muscular dystrophy, congenital myopathy to ?Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2, OMIM:615422; inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2, MONDO:0014178
Early onset or syndromic epilepsy v3.8 FRMD5 Arina Puzriakova gene: FRMD5 was added
gene: FRMD5 was added to Genetic epilepsy syndromes. Sources: Literature
Q4_22_promote_green tags were added to gene: FRMD5.
Mode of inheritance for gene: FRMD5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FRMD5 were set to 36206744
Phenotypes for gene: FRMD5 were set to Neurodevelopmental disorder with eye movement abnormalities and ataxia, OMIM:620094
Review for gene: FRMD5 was set to GREEN
Added comment: Lu et al. 2022 (PMID: 36206744) report 8 unrelated individuals with de novo missense FRMD5 variants who presented with developmental delay (8/8), intellectual disability (7/7), ataxia (7/8), seizures (5/8), and abnormalities of eye movement (8/8). LOF mutant flies exhibited motor impairment, defective responses to light and heat-induced seizures. Fly phenotypes were rescued by expression of the wildtype gene but not by two of the patient missense mutants.

FRMD5 is associated with a relevant phenotype in OMIM (MIM# 620094) but is not yet listed in G2P.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v3.17 FRMD5 Arina Puzriakova gene: FRMD5 was added
gene: FRMD5 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Q4_22_promote_green tags were added to gene: FRMD5.
Mode of inheritance for gene: FRMD5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FRMD5 were set to 36206744
Phenotypes for gene: FRMD5 were set to Neurodevelopmental disorder with eye movement abnormalities and ataxia, OMIM:620094
Review for gene: FRMD5 was set to GREEN
Added comment: Lu et al. 2022 (PMID: 36206744) report 8 unrelated individuals with de novo missense FRMD5 variants who presented with developmental delay (8/8), intellectual disability (7/7), ataxia (7/8), seizures (5/8), and abnormalities of eye movement (8/8). LOF mutant flies exhibited motor impairment, defective responses to light and heat-induced seizures. Fly phenotypes were rescued by expression of the wildtype gene but not by two of the patient missense mutants.

FRMD5 is associated with a relevant phenotype in OMIM (MIM# 620094) but is not yet listed in G2P.
Sources: Literature
Intellectual disability v4.14 FRMD5 Arina Puzriakova gene: FRMD5 was added
gene: FRMD5 was added to Intellectual disability. Sources: Literature
Q4_22_promote_green tags were added to gene: FRMD5.
Mode of inheritance for gene: FRMD5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FRMD5 were set to 36206744
Phenotypes for gene: FRMD5 were set to Neurodevelopmental disorder with eye movement abnormalities and ataxia, OMIM:620094
Review for gene: FRMD5 was set to GREEN
Added comment: Lu et al. 2022 (PMID: 36206744) report 8 unrelated individuals with de novo missense FRMD5 variants who presented with developmental delay (8/8), intellectual disability (7/7), ataxia (7/8), seizures (5/8), and abnormalities of eye movement (8/8). LOF mutant flies exhibited motor impairment, defective responses to light and heat-induced seizures. Fly phenotypes were rescued by expression of the wildtype gene but not by two of the patient missense mutants.

FRMD5 is associated with a relevant phenotype in OMIM (MIM# 620094) but is not yet listed in G2P.
Sources: Literature
Congenital muscular dystrophy v3.8 HNRNPA2B1 Sarah Leigh Publications for gene: HNRNPA2B1 were set to https://www.nmd-journal.com/article/S0960-8966(20)30203-0/fulltext
Ataxia and cerebellar anomalies - narrow panel v3.16 CAPRIN1 Dmitrijs Rots gene: CAPRIN1 was added
gene: CAPRIN1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: CAPRIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAPRIN1 were set to 36136249
Phenotypes for gene: CAPRIN1 were set to Infantile-onset ataxia
Penetrance for gene: CAPRIN1 were set to Complete
Mode of pathogenicity for gene: CAPRIN1 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: CAPRIN1 was set to GREEN
Added comment: CAPRIN1 is reported in two indepedent cases with infantile-onset ataxia and cognitive decline (reported 2 de novo in two cases + functional evidence, so enough evidence for green rating).
Sources: Literature
Intellectual disability v4.13 CAPRIN1 Dmitrijs Rots reviewed gene: CAPRIN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 36136249; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v3.16 NPTX1 Dmitrijs Rots gene: NPTX1 was added
gene: NPTX1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: NPTX1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NPTX1 were set to 34788392; 35285082; 35560436
Phenotypes for gene: NPTX1 were set to Ataxia
Penetrance for gene: NPTX1 were set to unknown
Mode of pathogenicity for gene: NPTX1 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: NPTX1 was set to GREEN
Added comment: Multiple individiuals with de novo or inherited (segregating with the phenotype) NPTX1 reported in the literature with both late and infantile-onset ataxia. Enough evidence for green.

The phenotype is described in 34788392 as:
"The NPTX1-associated phenotype consists of a late-onset, slowly progressive, cerebellar ataxia, with downbeat nystagmus, cognitive impairment reminiscent of cerebellar cognitive affective syndrome, myoclonic tremor and mild cerebellar vermian atrophy on brain imaging."
Sources: Literature
Intellectual disability v4.13 BUB1 Sarah Leigh edited their review of gene: BUB1: Added comment: Not associated with a phenotype in OMIM, but has a moderate association with BUB1-related microcephaly and developmental disorder in Gen2Phen. PMID: 35044816 reports three BUB1 variants in two cases of developmental delay, including microcephaly, together with supportive functional studies.; Changed rating: GREEN
BAP1 associated tumour predisposition syndrome v0.0 Eleanor Williams Added Panel BAP1 associated tumour predisposition syndrome
Set list of related panels to R422
Autoimmune Polyendocrine Syndrome v0.0 Eleanor Williams Added Panel Autoimmune Polyendocrine Syndrome
Set list of related panels to R155
Autoimmune lymphoproliferative syndrome with defective apoptosis v0.0 Eleanor Williams Added Panel Autoimmune lymphoproliferative syndrome with defective apoptosis
Set list of related panels to R19
Ataxia telangiectasia - mutation testing v0.0 Eleanor Williams Added Panel Ataxia telangiectasia - mutation testing
Set list of related panels to R295
APC associated Polyposis v0.0 Eleanor Williams Added Panel APC associated Polyposis
Set list of related panels to R414
Alveolar capillary dysplasia with misalignment of pulmonary veins v0.0 Eleanor Williams Added Panel Alveolar capillary dysplasia with misalignment of pulmonary veins
Set list of related panels to R330
Alstrom syndrome v0.0 Eleanor Williams Added Panel Alstrom syndrome
Set list of related panels to R106
Albright hereditary osteodystrophy, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, acrodysostosis and osteoma cutis v0.0 Eleanor Williams Added Panel Albright hereditary osteodystrophy, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, acrodysostosis and osteoma cutis
Set list of related panels to R293
Agammaglobulinaemia with absent BTK expression v0.0 Eleanor Williams Added Panel Agammaglobulinaemia with absent BTK expression
Set list of related panels to R233
Acute intermittent porphyria v0.0 Eleanor Williams Added Panel Acute intermittent porphyria
Set list of related panels to R169
Congenital myaesthenic syndrome v3.3 TOR1AIP1 Arina Puzriakova changed review comment from: At least 5 individuals from 2 unrelated families reported (PMID: 33215087; 34164833) specifically with a myasthenic syndrome in association with different homozygous LoF variants in this gene (c.127delC, p.Pro43fs and c.63dupC, p.Arg22Glnfs*88, respectively). Electromyography in patients revealed decremental responses on repetitive nerve stimulation. Muscle biopsy from one proband showed the protein encoded by TOR1AIP1 was absent in myonuclei.
Knockout mice exhibited fatigable muscle weakness and also decrement on repetitive nerve stimulation. Neuromuscular junctions were enlarged and fragmented, and the number of subsynaptic nuclei was significantly increased signifying impaired synaptic transmission.; to: At least 5 individuals from 2 unrelated families reported (PMID: 33215087; 34164833) specifically with a myasthenic syndrome in association with different homozygous LoF variants in this gene (c.127delC, p.Pro43fs and c.63dupC, p.Arg22Glnfs*88, respectively). Electromyography in patients revealed decremental responses on repetitive nerve stimulation. Muscle biopsy from one proband showed the protein encoded by TOR1AIP1 was absent in myonuclei. Both variants were shown to truncate the muscle isoform (termed LAP1B) while the LAP1C isoform remained intact.
Knockout mice exhibited fatigable muscle weakness and also decrement on repetitive nerve stimulation. Neuromuscular junctions were enlarged and fragmented, and the number of subsynaptic nuclei was significantly increased signifying impaired synaptic transmission.
Intellectual disability v4.13 SLC35F1 Arina Puzriakova Classified gene: SLC35F1 as Red List (low evidence)
Intellectual disability v4.13 SLC35F1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). Rating Red as only a single patient with a heterozygous missense variant has been reported to date (PMID:33821533). Limited information on the SLC35F1 gene is known in general.
Intellectual disability v4.13 SLC35F1 Arina Puzriakova Gene: slc35f1 has been classified as Red List (Low Evidence).
Paediatric or syndromic cardiomyopathy v2.1 KBTBD13 Dmitrijs Rots gene: KBTBD13 was added
gene: KBTBD13 was added to Cardiomyopathies - including childhood onset. Sources: Literature
Mode of inheritance for gene: KBTBD13 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KBTBD13 were set to 36335629
Penetrance for gene: KBTBD13 were set to Incomplete
Mode of pathogenicity for gene: KBTBD13 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: KBTBD13 was set to GREEN
Added comment: 3 families with cardiomyopathy and other related cardiac phenotypes reported in 36335629 with mouse model. Enough evidence for green. All cases had p.R408C variant.
Sources: Literature
Malformations of cortical development v3.2 PAFAH1B1 Achchuthan Shanmugasundram Publications for gene: PAFAH1B1 were set to
Malformations of cortical development v3.1 PAFAH1B1 Achchuthan Shanmugasundram reviewed gene: PAFAH1B1: Rating: ; Mode of pathogenicity: None; Publications: 34635911; Phenotypes: ; Mode of inheritance: None
Early onset or syndromic epilepsy v3.7 GPHN Achchuthan Shanmugasundram Phenotypes for gene: GPHN were changed from Molybdenum cofactor deficiency C, OMIM:615501 to Molybdenum cofactor deficiency C, OMIM:615501; Developmental and epileptic encephalopathy, MONDO:0100062
Early onset or syndromic epilepsy v3.6 GPHN Achchuthan Shanmugasundram Publications for gene: GPHN were set to 26613940; 12684523; 11095995; 22040219; 24561070; 23393157
Early onset or syndromic epilepsy v3.5 GPHN Achchuthan Shanmugasundram reviewed gene: GPHN: Rating: GREEN; Mode of pathogenicity: None; Publications: 34617111; Phenotypes: Developmental and epileptic encephalopathy, MONDO:0100062; Mode of inheritance: None
Intellectual disability v4.12 BUB1 Sarah Leigh Tag Q4_22_MOI tag was added to gene: BUB1.
Tag Q4_22_promote_green tag was added to gene: BUB1.
Intellectual disability v4.12 BUB1 Sarah Leigh Classified gene: BUB1 as Amber List (moderate evidence)
Intellectual disability v4.12 BUB1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Intellectual disability v4.12 BUB1 Sarah Leigh Gene: bub1 has been classified as Amber List (Moderate Evidence).
Congenital myopathy v3.10 KY Sarah Leigh commented on gene: KY: Associated with Myopathy, myofibrillar, 7 (OMIM: 617114) in OMIM, but not associated with phenotype in Gen2Phen. At least 4 variants have been reported in unrelated cases. PMID: 30591934 demostrates segregation of KY c.415C>T (p.R139*) in the affected homozygous members of a consanguineous family, where the parents are heterozygotes and the unaffected sister is homozygous for the wild type allele. PMID 27485408 describes the spontaneously generated murine ortholog of variant Ky with postnatally developing kyphoscoliosis, the authors note the similarities between the patient and mouse muscle fibres.
Congenital myopathy v3.10 TNNC2 Sarah Leigh reviewed gene: TNNC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Clefting v3.2 MYCN Achchuthan Shanmugasundram gene: MYCN was added
gene: MYCN was added to Clefting. Sources: Literature
Mode of inheritance for gene: MYCN was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MYCN were set to 34590686
Phenotypes for gene: MYCN were set to Cleft lip with or without cleft palate, MONDO:0016034
Review for gene: MYCN was set to RED
Added comment: Comment on classification of this gene: This gene has been added with a RED rating to this panel, as identified from one case and supported by functional studies with mouse model.

Out of the 104 multiplex families with Mendelian non-syndromic cleft lip with or without cleft palate (NSCL/P), a novel pathogenic variant (c.703G>C/ p.A235P) has been identified in MYCN gene from one family. This variant was found in the proband and his affected mother and absent in the unaffected sister, showing co-segregation with phenotype in this family.

In addition, experimental evidence from conditional knockout mouse model showed that these mice displayed cleft palate, microglossia and micrognathia, resembling the Pierre Robin sequence (PRS) in humans.

This gene has not yet been associated with clefting either in OMIM or in Gene2Phenotype.
Sources: Literature
Congenital myopathy v3.10 UNC45B Sarah Leigh Tag Q4_22_promote_green tag was added to gene: UNC45B.
Tag Q4_22_expert_review tag was added to gene: UNC45B.
Tag Q4_22_NHS_review tag was added to gene: UNC45B.
Congenital myopathy v3.10 UNC45B Sarah Leigh commented on gene: UNC45B: Associated with relevant Myofibrillar myopathy 11 in OMIM and as strong Gen2Phen gene for UNC45B-associated Progressive Myopathy with Eccentric Cores. At least 7 variants have been reported in at least 10 unrelated families. SEgregation has been observed and functional studies suggest that reduced expression of UNC45B is associated with Myofibrillar myopathy 11. This review represents further information from subsequent case reports and the update of OMIM to allow OMIM asign a phenotype tp this gene.
Congenital myopathy v3.10 UNC45B Sarah Leigh Phenotypes for gene: UNC45B were changed from Progressive Myopathy with Eccentric Cores to Myofibrillar myopathy 11, OMIM:619178; myofibrillar myopathy 11, MONDO:0030927
Congenital myopathy v3.9 UNC45B Sarah Leigh Publications for gene: UNC45B were set to 33217308
Early onset or syndromic epilepsy v3.5 SNIP1 Sarah Leigh Publications for gene: SNIP1 were set to 22279524; 34570759
Mitochondrial disorders v3.2 TARS2 Achchuthan Shanmugasundram Phenotypes for gene: TARS2 were changed from Combined oxidative phosphorylation deficiency 21, OMIM:615918 to Combined oxidative phosphorylation deficiency 21, OMIM:615918, MONDO:0014398
Mitochondrial disorders v3.1 TARS2 Achchuthan Shanmugasundram reviewed gene: TARS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 34508595; Phenotypes: Combined oxidative phosphorylation deficiency 21, MIM# 615918, MONDO:0014398; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
White matter disorders and cerebral calcification - narrow panel v2.3 PDGFRB Achchuthan Shanmugasundram edited their review of gene: PDGFRB: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
White matter disorders and cerebral calcification - narrow panel v2.3 PDGFRB Achchuthan Shanmugasundram Publications for gene: PDGFRB were set to 23255827 - original family report and sproadic case report; 24796542 - an additional case report of a idiopathic basal ganglia calcification patient with the p.R695C mutation, which resulted in partial loss of autophosphorylation; 25292412 - functional studies; 26599395 - mouse models and functional studies; 26129893
White matter disorders and cerebral calcification - narrow panel v2.2 PDGFRB Achchuthan Shanmugasundram reviewed gene: PDGFRB: Rating: GREEN; Mode of pathogenicity: None; Publications: 34494111; Phenotypes: Basal ganglia calcification, idiopathic, 4, MIM# 615007, MONDO:0014004; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe microcephaly v3.2 TPR Achchuthan Shanmugasundram gene: TPR was added
gene: TPR was added to Severe microcephaly. Sources: Literature
Mode of inheritance for gene: TPR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TPR were set to 34494102
Phenotypes for gene: TPR were set to Microcephaly, MONDO:0001149
Review for gene: TPR was set to RED
Added comment: Comment on classification of this gene: This gene should be added with a RED rating as the association of TPR to microcephaly is based on biallelic variants identified from a report of two siblings.

Two siblings harbouring variants c.6625C>T/ p.Arg2209Ter (identified in heterozygous state in both siblings and father) and c.2610 + 5G > A (identified in heterozygous state in both siblings and mother) were reported with ataxia, microcephaly and severe intellectual disability. The occipitofrontal circumference (OFC) was at 3rd centile for individual 1 and at 10th centile for individual 2 and dropped to below 1st centile at eight months and five months respectively.

Functional analyses in patient fibroblasts provide evidence that the variants affect TPR splicing, reduce steady-state TPR levels, abnormal nuclear pore composition and density, and altered global RNA distribution.

This gene has not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v3.16 TPR Achchuthan Shanmugasundram edited their review of gene: TPR: Changed rating: RED
Ataxia and cerebellar anomalies - narrow panel v3.16 TPR Achchuthan Shanmugasundram gene: TPR was added
gene: TPR was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: TPR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TPR were set to 34494102
Phenotypes for gene: TPR were set to Cerebellar ataxia, MONDO:0000437
Added comment: Comment on classification of this gene: This gene should be added with a RED rating as the association of TPR to ataxia is based on biallelic variants identified from a report of two siblings.

Two siblings harbouring variants c.6625C>T/ p.Arg2209Ter (identified in heterozygous state in both siblings and father) and c.2610 + 5G > A (identified in heterozygous state in both siblings and mother) were reported with ataxia, microcephaly and severe intellectual disability.

Functional analyses in patient fibroblasts provide evidence that the variants affect TPR splicing, reduce steady-state TPR levels, abnormal nuclear pore composition and density, and altered global RNA distribution.

This gene has not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v4.11 TPR Achchuthan Shanmugasundram gene: TPR was added
gene: TPR was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: TPR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TPR were set to 34494102
Phenotypes for gene: TPR were set to Intellectual disability, MONDO:0001071
Review for gene: TPR was set to RED
Added comment: Comment on classification of this gene: This gene should be added with a RED rating as the association of TPR to intellectual disability is based on biallelic variants identified from a report of two siblings.

Two siblings harbouring variants c.6625C>T/ p.Arg2209Ter (identified in heterozygous state in both siblings and father) and c.2610 + 5G > A (identified in heterozygous state in both siblings and mother) were reported with ataxia, microcephaly and severe intellectual disability.

Functional analyses in patient fibroblasts provide evidence that the variants affect TPR splicing, reduce steady-state TPR levels, abnormal nuclear pore composition and density, and altered global RNA distribution.

This gene has not yet been associated with any phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Neurofibromatosis Type 1 v1.32 NF1 Achchuthan Shanmugasundram reviewed gene: NF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34476477; Phenotypes: Neurofibromatosis, type 1, MIM# 162200, MONDO:0018975, Renovascular hypertension, MONDO:0006947; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Renal ciliopathies v2.2 NPHP1 Achchuthan Shanmugasundram Publications for gene: NPHP1 were set to 15138899; 22982934; 15689444
Renal ciliopathies v2.1 NPHP1 Achchuthan Shanmugasundram reviewed gene: NPHP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34415307; Phenotypes: ; Mode of inheritance: None
Retinal disorders v3.2 NPHP1 Achchuthan Shanmugasundram Publications for gene: NPHP1 were set to
Retinal disorders v3.1 NPHP1 Achchuthan Shanmugasundram reviewed gene: NPHP1: Rating: ; Mode of pathogenicity: None; Publications: 34415307; Phenotypes: ; Mode of inheritance: None
Unexplained young onset end-stage renal disease v2.3 NPHP1 Achchuthan Shanmugasundram Publications for gene: NPHP1 were set to 266900; 34415307
Unexplained young onset end-stage renal disease v2.2 NPHP1 Achchuthan Shanmugasundram Publications for gene: NPHP1 were set to 266900
Unexplained young onset end-stage renal disease v2.1 NPHP1 Achchuthan Shanmugasundram reviewed gene: NPHP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34415307; Phenotypes: ; Mode of inheritance: None
Unexplained kidney failure in young people v1.116 NPHP1 Achchuthan Shanmugasundram reviewed gene: NPHP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34415307; Phenotypes: ; Mode of inheritance: None
Cystic kidney disease v3.2 NPHP1 Achchuthan Shanmugasundram Publications for gene: NPHP1 were set to
Cystic kidney disease v3.1 NPHP1 Achchuthan Shanmugasundram reviewed gene: NPHP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34415307; Phenotypes: ; Mode of inheritance: None
Tubulointerstitial kidney disease v2.2 NPHP1 Achchuthan Shanmugasundram Publications for gene: NPHP1 were set to
Tubulointerstitial kidney disease v2.1 NPHP1 Achchuthan Shanmugasundram reviewed gene: NPHP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34415307; Phenotypes: ; Mode of inheritance: None
Congenital muscular dystrophy v3.7 GOSR2 Achchuthan Shanmugasundram Tag Q4_22_promote_green tag was added to gene: GOSR2.
Congenital muscular dystrophy v3.7 GOSR2 Achchuthan Shanmugasundram Publications for gene: GOSR2 were set to 29855340
Congenital muscular dystrophy v3.6 GOSR2 Achchuthan Shanmugasundram Classified gene: GOSR2 as Amber List (moderate evidence)
Congenital muscular dystrophy v3.6 GOSR2 Achchuthan Shanmugasundram Gene: gosr2 has been classified as Amber List (Moderate Evidence).
Congenital muscular dystrophy v3.5 GOSR2 Achchuthan Shanmugasundram reviewed gene: GOSR2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29855340, 33639315, 34167170; Phenotypes: Congenital muscular dystrophy, MONDO:0019950; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v3.4 BET1 Achchuthan Shanmugasundram Phenotypes for gene: BET1 were changed from Epilepsy; congenical musculara dystrophy to Epilepsy, MONDO:0005027
Early onset or syndromic epilepsy v3.3 BET1 Achchuthan Shanmugasundram Publications for gene: BET1 were set to PMID: 34779586
Early onset or syndromic epilepsy v3.2 BET1 Achchuthan Shanmugasundram Classified gene: BET1 as Red List (low evidence)
Early onset or syndromic epilepsy v3.2 BET1 Achchuthan Shanmugasundram Gene: bet1 has been classified as Red List (Low Evidence).
Early onset or syndromic epilepsy v3.1 BET1 Achchuthan Shanmugasundram reviewed gene: BET1: Rating: RED; Mode of pathogenicity: None; Publications: 34779586; Phenotypes: Epilepsy, MONDO:0005027; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital muscular dystrophy v3.5 BET1 Achchuthan Shanmugasundram Tag Q4_22_promote_green tag was added to gene: BET1.
Congenital muscular dystrophy v3.5 BET1 Achchuthan Shanmugasundram Phenotypes for gene: BET1 were changed from Congenital muscular dystrophy with epilepsy to Congenital muscular dystrophy, MONDO:0019950
Congenital muscular dystrophy v3.4 BET1 Achchuthan Shanmugasundram Publications for gene: BET1 were set to
Congenital muscular dystrophy v3.3 BET1 Achchuthan Shanmugasundram Classified gene: BET1 as Amber List (moderate evidence)
Congenital muscular dystrophy v3.3 BET1 Achchuthan Shanmugasundram Gene: bet1 has been classified as Amber List (Moderate Evidence).
Congenital muscular dystrophy v3.3 BET1 Achchuthan Shanmugasundram Classified gene: BET1 as Amber List (moderate evidence)
Congenital muscular dystrophy v3.3 BET1 Achchuthan Shanmugasundram Gene: bet1 has been classified as Amber List (Moderate Evidence).
Congenital muscular dystrophy v3.3 BET1 Achchuthan Shanmugasundram Classified gene: BET1 as Amber List (moderate evidence)
Congenital muscular dystrophy v3.3 BET1 Achchuthan Shanmugasundram Gene: bet1 has been classified as Amber List (Moderate Evidence).
Congenital muscular dystrophy v3.2 BET1 Achchuthan Shanmugasundram Classified gene: BET1 as Amber List (moderate evidence)
Congenital muscular dystrophy v3.2 BET1 Achchuthan Shanmugasundram Gene: bet1 has been classified as Amber List (Moderate Evidence).
Congenital muscular dystrophy v3.2 BET1 Achchuthan Shanmugasundram Classified gene: BET1 as Amber List (moderate evidence)
Congenital muscular dystrophy v3.2 BET1 Achchuthan Shanmugasundram Gene: bet1 has been classified as Amber List (Moderate Evidence).
Congenital muscular dystrophy v3.1 BET1 Achchuthan Shanmugasundram reviewed gene: BET1: Rating: GREEN; Mode of pathogenicity: None; Publications: 34779586; Phenotypes: Congenital muscular dystrophy, MONDO:0019950; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.10 BAP1 Mafalda Gomes edited their review of gene: BAP1: Changed phenotypes to: Kury-Isidor syndrome, OMIM:619762
Early onset or syndromic epilepsy v3.1 BAP1 Mafalda Gomes edited their review of gene: BAP1: Changed phenotypes to: Kury-Isidor syndrome, OMIM:619762
Early onset or syndromic epilepsy v3.1 BAP1 Mafalda Gomes edited their review of gene: BAP1: Changed rating: GREEN
Early onset or syndromic epilepsy v3.1 BAP1 Mafalda Gomes gene: BAP1 was added
gene: BAP1 was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: BAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: BAP1 were set to 35051358
Added comment: Küry et al. (2022) performed trio-WES in a cohort with a rare syndromic NDD and identified de novo missense variants in 11 unrelated individuals. All individuals had DD or ID characterised notably by speech (11/11) and motor delay (6/11). Additional common characteristics were hypotonia, (7/11), seizures (6/11), and abnormal behaviour (8/10), including ASD, ADHD, and hypersensitivity. Almost all individuals showed dysmorphic facial features (10/11), and more than half (6/11) had skeletal malformations involving the hands, feet, or spine. Functional analysis showed that most of the variants cannot rescue the consequences of BAP1 inactivation, suggesting a loss-of-function mechanism. In T cells isolated from two affected children, H2A deubiquitination was impaired. In summary, this gene should be promoted to GREEN in this panel, with autosomal dominant mode of inheritance.
Sources: Literature
Intellectual disability v4.10 BAP1 Mafalda Gomes reviewed gene: BAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35051358; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb disorders v3.4 SUFU Arina Puzriakova Classified gene: SUFU as Amber List (moderate evidence)
Limb disorders v3.4 SUFU Arina Puzriakova Added comment: Comment on list classification: Recessive phenotype fits the scope of this panel; however only two cases have been reported to date in a single paper. Monoallelic form does not appear to feature skeletal abnormalities but rather is dominated by neurological phenotypes. Therefore maintaining Amber rating and biallelic MOI on this panel but adding a watchlist tag.
Limb disorders v3.4 SUFU Arina Puzriakova Gene: sufu has been classified as Amber List (Moderate Evidence).
Limb disorders v3.3 SUFU Arina Puzriakova Tag watchlist tag was added to gene: SUFU.
Limb disorders v3.3 SUFU Arina Puzriakova reviewed gene: SUFU: Rating: AMBER; Mode of pathogenicity: None; Publications: 21289193, 28965847, 33024317, 34675124; Phenotypes: Joubert syndrome 32, OMIM:617757; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Skeletal ciliopathies v2.3 SUFU Arina Puzriakova Classified gene: SUFU as Amber List (moderate evidence)
Skeletal ciliopathies v2.3 SUFU Arina Puzriakova Added comment: Comment on list classification: Recessive phenotype fits the scope of this panel; however only two cases have been reported to date in a single paper. Monoallelic form does not appear to feature skeletal abnormalities but rather is dominated by neurological phenotypes. Therefore maintaining Amber rating and biallelic MOI on this panel but adding a watchlist tag.
Skeletal ciliopathies v2.3 SUFU Arina Puzriakova Gene: sufu has been classified as Amber List (Moderate Evidence).
Skeletal ciliopathies v2.2 SUFU Arina Puzriakova Tag watchlist tag was added to gene: SUFU.
Skeletal ciliopathies v2.2 SUFU Arina Puzriakova reviewed gene: SUFU: Rating: AMBER; Mode of pathogenicity: None; Publications: 21289193, 28965847, 33024317, 34675124; Phenotypes: Joubert syndrome 32, OMIM:617757; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Rare multisystem ciliopathy disorders v1.168 SUFU Arina Puzriakova Publications for gene: SUFU were set to 28965847
Rare multisystem ciliopathy disorders v1.167 SUFU Arina Puzriakova Classified gene: SUFU as Green List (high evidence)
Rare multisystem ciliopathy disorders v1.167 SUFU Arina Puzriakova Added comment: Comment on list classification: Upgraded from Amber to Green under a monoallelic MOI - sufficient unrelated cases with heterozygous variants and a comparable phenotype within the Joubert spectrum.
Rare multisystem ciliopathy disorders v1.167 SUFU Arina Puzriakova Gene: sufu has been classified as Green List (High Evidence).
Rare multisystem ciliopathy disorders v1.166 SUFU Arina Puzriakova Added comment: Comment on mode of inheritance: Following consultation with Helen Brittain (Genomics England Clinical team) it was decided that based on the current evidence the MOI should be set to 'monoallelic' only for now but with a 'watchlist' tag to monitor for additional biallelic cases relating to a Joubert-like presentation.
Rare multisystem ciliopathy disorders v1.166 SUFU Arina Puzriakova Mode of inheritance for gene: SUFU was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rare multisystem ciliopathy disorders v1.165 SUFU Arina Puzriakova Tag watchlist was removed from gene: SUFU.
Tag watchlist_moi tag was added to gene: SUFU.
Rare multisystem ciliopathy disorders v1.165 SUFU Arina Puzriakova reviewed gene: SUFU: Rating: GREEN; Mode of pathogenicity: None; Publications: 21289193, 28965847, 33024317, 34675124; Phenotypes: Joubert syndrome 32, OMIM:617757; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v3.15 SUFU Arina Puzriakova Entity copied from Neurological ciliopathies v2.4
Ataxia and cerebellar anomalies - narrow panel v3.15 SUFU Arina Puzriakova gene: SUFU was added
gene: SUFU was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Expert list,Expert Review Amber
watchlist_moi, Q4_22_MOI, Q4_22_promote_green tags were added to gene: SUFU.
Mode of inheritance for gene: SUFU was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SUFU were set to 21289193; 28965847; 33024317; 34675124
Phenotypes for gene: SUFU were set to Joubert syndrome 32, OMIM:617757
Ophthalmological ciliopathies v2.4 SUFU Arina Puzriakova Publications for gene: SUFU were set to 28965847
Ophthalmological ciliopathies v2.3 SUFU Arina Puzriakova Classified gene: SUFU as Amber List (moderate evidence)
Ophthalmological ciliopathies v2.3 SUFU Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update under a MONOALLELIC inheritance pattern only, unless the NHS GMS working group disagree and feel the MOI should include both mono- and biallelic variants based on the current evidence.
Ophthalmological ciliopathies v2.3 SUFU Arina Puzriakova Gene: sufu has been classified as Amber List (Moderate Evidence).
Ophthalmological ciliopathies v2.2 SUFU Arina Puzriakova Added comment: Comment on mode of inheritance: Following consultation with Helen Brittain (Genomics England Clinical team) it was decided that based on the current evidence the MOI should be set to 'monoallelic' only for now but with a 'watchlist' tag to monitor for additional biallelic cases relating to a Joubert-like presentation.
Ophthalmological ciliopathies v2.2 SUFU Arina Puzriakova Mode of inheritance for gene: SUFU was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ophthalmological ciliopathies v2.1 SUFU Arina Puzriakova Tag watchlist_moi tag was added to gene: SUFU.
Tag Q4_22_MOI tag was added to gene: SUFU.
Tag Q4_22_promote_green tag was added to gene: SUFU.
Ophthalmological ciliopathies v2.1 SUFU Arina Puzriakova reviewed gene: SUFU: Rating: GREEN; Mode of pathogenicity: None; Publications: 21289193, 28965847, 33024317, 34675124; Phenotypes: Joubert syndrome 32, OMIM:617757; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Neurological ciliopathies v2.4 SUFU Arina Puzriakova Classified gene: SUFU as Amber List (moderate evidence)
Neurological ciliopathies v2.4 SUFU Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update under a MONOALLELIC inheritance pattern only, unless the NHS GMS working group disagree and feel the MOI should include both mono- and biallelic variants based on the current evidence.
Neurological ciliopathies v2.4 SUFU Arina Puzriakova Gene: sufu has been classified as Amber List (Moderate Evidence).
Neurological ciliopathies v2.3 SUFU Arina Puzriakova Added comment: Comment on mode of inheritance: Following consultation with Helen Brittain (Genomics England Clinical team) it was decided that based on the current evidence the MOI should be set to 'monoallelic' only for now but with a 'watchlist' tag to monitor for additional biallelic cases relating to a Joubert-like presentation.
Neurological ciliopathies v2.3 SUFU Arina Puzriakova Mode of inheritance for gene: SUFU was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Neurological ciliopathies v2.2 SUFU Arina Puzriakova Tag watchlist_moi tag was added to gene: SUFU.
Tag Q4_22_MOI tag was added to gene: SUFU.
Tag Q4_22_promote_green tag was added to gene: SUFU.
Neurological ciliopathies v2.2 SUFU Arina Puzriakova reviewed gene: SUFU: Rating: GREEN; Mode of pathogenicity: None; Publications: 21289193, 28965847, 33024317, 34675124; Phenotypes: Joubert syndrome 32, OMIM:617757; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v4.10 SUFU Arina Puzriakova edited their review of gene: SUFU: Changed publications to: 21289193, 28965847, 33024317, 34675124
Intellectual disability v4.10 SUFU Arina Puzriakova Penetrance for gene SUFU was set from to None
Intellectual disability v4.9 SUFU Arina Puzriakova Classified gene: SUFU as Amber List (moderate evidence)
Intellectual disability v4.9 SUFU Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update under a MONOALLELIC inheritance pattern only, unless the NHS GMS working group disagree and feel the MOI should include both mono- and biallelic variants based on the current evidence.
Intellectual disability v4.9 SUFU Arina Puzriakova Gene: sufu has been classified as Amber List (Moderate Evidence).
Neurological ciliopathies v2.2 SUFU Arina Puzriakova Publications for gene: SUFU were set to
Intellectual disability v4.8 SUFU Arina Puzriakova Publications for gene: SUFU were set to 21289193; 28965847; 33024317, 34675124
Intellectual disability v4.7 SUFU Arina Puzriakova Added comment: Comment on mode of inheritance: Following consultation with Helen Brittain (Genomics England Clinical team) it was decided that based on the current evidence the MOI should be set to 'monoallelic' only for now but with a 'watchlist' tag to monitor for additional biallelic cases relating to a Joubert-like presentation.
Intellectual disability v4.7 SUFU Arina Puzriakova Mode of inheritance for gene: SUFU was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v4.6 SUFU Arina Puzriakova Publications for gene: SUFU were set to 28965847; 30914295
Intellectual disability v4.5 SUFU Arina Puzriakova Phenotypes for gene: SUFU were changed from Joubert syndrome 32, 617757 to Joubert syndrome 32, OMIM:617757
Intellectual disability v4.4 SUFU Arina Puzriakova Tag Q4_22_MOI tag was added to gene: SUFU.
Intellectual disability v4.4 SUFU Arina Puzriakova Tag watchlist was removed from gene: SUFU.
Tag watchlist_moi tag was added to gene: SUFU.
Tag Q4_22_promote_green tag was added to gene: SUFU.
Intellectual disability v4.4 SUFU Arina Puzriakova edited their review of gene: SUFU: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v4.4 SUFU Arina Puzriakova reviewed gene: SUFU: Rating: GREEN; Mode of pathogenicity: None; Publications: 21289193, 28965847, 33024317, 34675124; Phenotypes: Joubert syndrome 32, OMIM:617757; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rhabdomyolysis and metabolic muscle disorders v2.3 MLIP Achchuthan Shanmugasundram Tag Q4_22_promote_green tag was added to gene: MLIP.
Rhabdomyolysis and metabolic muscle disorders v2.3 MLIP Achchuthan Shanmugasundram Classified gene: MLIP as Amber List (moderate evidence)
Rhabdomyolysis and metabolic muscle disorders v2.3 MLIP Achchuthan Shanmugasundram Gene: mlip has been classified as Amber List (Moderate Evidence).
Rhabdomyolysis and metabolic muscle disorders v2.2 MLIP Achchuthan Shanmugasundram gene: MLIP was added
gene: MLIP was added to Rhabdomyolysis and metabolic muscle disorders. Sources: Literature
Mode of inheritance for gene: MLIP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MLIP were set to 34581780; 34935254; 35672413; 35915960; 35942668
Phenotypes for gene: MLIP were set to Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis, MIM# 620138
Review for gene: MLIP was set to GREEN
Added comment: Comment on classification of this gene: The rating for this gene should be added as GREEN, as this gene has been implicated in rhabdomyolysis, as identified from biallelic variants from four unrelated cases from multiple ethnicities.

Seven patients from six families carrying six different biallelic (either homozygous or compound heterozygous) variants in MLIP gene were presented with a consistent phenotype including mild muscle weakness, exercise-induced muscle pain, variable susceptibility to episodes of rhabdomyolysis (reported in five individuals from four families), and persistent basal elevated serum creatine kinase (CK) levels. The age of onset of symptoms ranged from 8 months to 7 years (PMID:34581780). However, patients carrying biallelic variants in MLIP gene were not reported with rhabdomyolysis in other studies (PMID:34935254; PMID:35672413; PMID:35915960).

The association of MLIP to rhabdomyolysis has now been documented in OMIM (#620138).
Sources: Literature
Cardiac arrhythmias - additional genes v2.3 MLIP Achchuthan Shanmugasundram edited their review of gene: MLIP: Changed phenotypes to: Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis, MIM# 620138, Arrhythmia, HP:0011675
Cardiac arrhythmias - additional genes v2.3 MLIP Achchuthan Shanmugasundram Phenotypes for gene: MLIP were changed from Arrhythmia, HP:0011675 to Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis, MIM# 620138; Arrhythmia, HP:0011675
Congenital myopathy v3.8 MLIP Achchuthan Shanmugasundram Phenotypes for gene: MLIP were changed from Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis; MIM# 620138 to Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis, MIM# 620138
Congenital myopathy v3.7 MLIP Achchuthan Shanmugasundram edited their review of gene: MLIP: Changed phenotypes to: Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis, MIM# 620138
Acute rhabdomyolysis v1.4 MLIP Achchuthan Shanmugasundram Tag Q4_22_promote_green tag was added to gene: MLIP.
Acute rhabdomyolysis v1.4 MLIP Achchuthan Shanmugasundram Phenotypes for gene: MLIP were changed from Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis; MIM# 620138 to Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis, MIM# 620138
Acute rhabdomyolysis v1.3 MLIP Achchuthan Shanmugasundram Classified gene: MLIP as Amber List (moderate evidence)
Acute rhabdomyolysis v1.3 MLIP Achchuthan Shanmugasundram Gene: mlip has been classified as Amber List (Moderate Evidence).
Acute rhabdomyolysis v1.2 MLIP Achchuthan Shanmugasundram edited their review of gene: MLIP: Changed phenotypes to: Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis, MIM# 620138
Acute rhabdomyolysis v1.2 MLIP Achchuthan Shanmugasundram gene: MLIP was added
gene: MLIP was added to Acute rhabdomyolysis. Sources: Literature
Mode of inheritance for gene: MLIP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MLIP were set to 34581780; 34935254; 35672413; 35915960; 35942668
Phenotypes for gene: MLIP were set to Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis; MIM# 620138
Review for gene: MLIP was set to GREEN
Added comment: Comment on classification of this gene: The rating for this gene should be added as GREEN, as this gene has been implicated in rhabdomyolysis, as identified from biallelic variants from four unrelated cases from multiple ethnicities.

Seven patients from six families carrying six different biallelic (either homozygous or compound heterozygous) variants in MLIP gene were presented with a consistent phenotype including mild muscle weakness, exercise-induced muscle pain, variable susceptibility to episodes of rhabdomyolysis (reported in five individuals from four families), and persistent basal elevated serum creatine kinase (CK) levels. The age of onset of symptoms ranged from 8 months to 7 years (PMID:34581780). However, patients carrying biallelic variants in MLIP gene were not reported with rhabdomyolysis in other studies (PMID:34935254; PMID:35672413; PMID:35915960).

The association of MLIP to rhabdomyolysis has now been documented in OMIM (#620138).
Sources: Literature
Cardiac arrhythmias - additional genes v2.2 MLIP Achchuthan Shanmugasundram gene: MLIP was added
gene: MLIP was added to Cardiac arrhythmias - additional genes. Sources: Literature
Mode of inheritance for gene: MLIP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MLIP were set to 26436652; 32719146; 33802236; 34581780; 34935254
Phenotypes for gene: MLIP were set to Arrhythmia, HP:0011675
Review for gene: MLIP was set to RED
Added comment: Comment on classification of this gene: The rating for this gene should be added as RED, as the implication of this gene in cardiac arrhythmias was identified from biallelic variants from only one family (despite a mild ventricular dysfunction in another unrelated individual). However, this is well supported by results from functional studies from human tissue samples and mouse models.

Five individuals from two different pedigrees carrying two different novel homozygous nonsense variants were reported with myopathy characterized by hyperCKemia and with absence of rhabdomyolysis. The age of onset of symptoms for the single patient from family 1 is 2.5 years. All four individuals (age ranges from 24 to 37) from family 2 (Amish ancestry) were reported either with Sinus arrhythmia or Sinus bradycardia and one of these individuals displayed left ventricular hypertrophy. It was also found that there is founder effect for this allele in the Amish population in the resident county of these individuals (PMID:34935254).

Seven patients from six families carrying six different biallelic (either homozygous or compound heterozygous) variants in MLIP gene were presented with a consistent phenotype including mild muscle weakness, exercise-induced muscle pain, variable susceptibility to episodes of rhabdomyolysis, and persistent basal elevated serum creatine kinase (CK) levels. The age of onset of symptoms ranged from 8 months to 7 years. However, mild left ventricular dysfunction was reported only in one patient, despite the presence of mild structural abnormalities in two other patients (PMID:34581780).

The expression of MLIP was identified to be reduced in patients with dilated cardiomyopathy, as studied from LV samples from patients with terminal-stage heart failure. In addition, deletion of MLIP gene accelerated progress from hypertrophy to heart failure in several cardiomyopathy models and overexpression prevented pathologic remodelling and preserved cardiac function (PMID:26436652). MLIP has also been identified as a regulator of myoblast differentiation (PMID:33802236) and myonuclear positioning (PMID:32719146).
Sources: Literature
Congenital myopathy v3.7 MLIP Achchuthan Shanmugasundram Tag Q4_22_promote_green tag was added to gene: MLIP.
Congenital myopathy v3.7 MLIP Achchuthan Shanmugasundram Phenotypes for gene: MLIP were changed from MLIP-related myopathy with rhabdomyolysis to Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis; MIM# 620138
Congenital myopathy v3.6 MLIP Achchuthan Shanmugasundram Publications for gene: MLIP were set to 26436652; 32719146; 33802236; 34581780; 34935254; 35672413; 35915960; 35942668
Congenital myopathy v3.6 MLIP Achchuthan Shanmugasundram Publications for gene: MLIP were set to 26436652; 32719146; 33802236; 34581780; 34935254; 35672413; 35915960; 35942668
Congenital myopathy v3.6 MLIP Achchuthan Shanmugasundram Publications for gene: MLIP were set to 26436652; 32719146; 33802236; 34581780; 34935254; 35672413; 35915960; 35942668
Congenital myopathy v3.5 MLIP Achchuthan Shanmugasundram Publications for gene: MLIP were set to 26436652; 32719146; 33802236; 34581780; 34935254; 35672413; 35915960; 35942668
Congenital myopathy v3.5 MLIP Achchuthan Shanmugasundram Publications for gene: MLIP were set to 26436652; 32719146; 33802236; 34581780; 34935254; 35672413; 35915960; 35942668
Congenital myopathy v3.5 MLIP Achchuthan Shanmugasundram Publications for gene: MLIP were set to 34581780
Congenital myopathy v3.4 MLIP Achchuthan Shanmugasundram Classified gene: MLIP as Amber List (moderate evidence)
Congenital myopathy v3.4 MLIP Achchuthan Shanmugasundram Gene: mlip has been classified as Amber List (Moderate Evidence).
Congenital myopathy v3.3 MLIP Achchuthan Shanmugasundram Classified gene: MLIP as Amber List (moderate evidence)
Congenital myopathy v3.3 MLIP Achchuthan Shanmugasundram Gene: mlip has been classified as Amber List (Moderate Evidence).
Congenital myopathy v3.2 MLIP Achchuthan Shanmugasundram reviewed gene: MLIP: Rating: GREEN; Mode of pathogenicity: None; Publications: 26436652, 32719146, 33802236, 34581780, 34935254, 35672413, 35915960, 35942668; Phenotypes: Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis, MIM# 620138; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital myopathy v3.2 CCDC78 Achchuthan Shanmugasundram Tag Q4_22_MOI tag was added to gene: CCDC78.
Congenital myopathy v3.2 CCDC78 Achchuthan Shanmugasundram Tag Q4_22_expert_review tag was added to gene: CCDC78.
Congenital myopathy v3.2 CCDC78 Achchuthan Shanmugasundram Tag Q4_22_demote_amber tag was added to gene: CCDC78.
Congenital myopathy v3.2 CCDC78 Achchuthan Shanmugasundram Publications for gene: CCDC78 were set to 22818856
Congenital myopathy v3.1 CCDC78 Achchuthan Shanmugasundram reviewed gene: CCDC78: Rating: AMBER; Mode of pathogenicity: None; Publications: 22818856, 25635128; Phenotypes: centronuclear myopathy-4, MIM# 614807; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Optic neuropathy v3.5 SLC52A2 Achchuthan Shanmugasundram Phenotypes for gene: SLC52A2 were changed from Brown-Vialetto-Van Laere syndrome 2, 614707 to Brown-Vialetto-Van Laere syndrome 2, MIM# 614707, MONDO:0013867; Optic atrophy, MONDO:0003608
Optic neuropathy v3.4 SLC52A2 Achchuthan Shanmugasundram Publications for gene: SLC52A2 were set to 23243084; 22864630
Optic neuropathy v3.3 SLC52A2 Achchuthan Shanmugasundram reviewed gene: SLC52A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22740598, 22864630, 23243084, 24253200, 30343981, 30377535, 31868069, 35608644, 36186484; Phenotypes: Brown-Vialetto-Van Laere syndrome 2, MIM# 614707, MONDO:0013867, Optic atrophy, MONDO:0003608; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v3.3 SLC52A2 Achchuthan Shanmugasundram Phenotypes for gene: SLC52A2 were changed from Brown-Vialetto-Van Laere syndrome 2, OMIM:614707 to Brown-Vialetto-Van Laere syndrome 2, OMIM:614707, MONDO:0013867; Sensorineural hearing loss disorder, MONDO:0020678
Monogenic hearing loss v3.2 SLC52A2 Achchuthan Shanmugasundram Publications for gene: SLC52A2 were set to 22740598; 22864630; 23243084; 24253200
Monogenic hearing loss v3.1 SLC52A2 Achchuthan Shanmugasundram reviewed gene: SLC52A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22740598, 22864630, 23243084, 24253200, 30343981, 30377535, 31868069, 35608644, 36186484; Phenotypes: Brown-Vialetto-Van Laere syndrome 2, MIM# 614707, MONDO:0013867, Sensorineural hearing loss disorder, MONDO:0020678; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v2.7 SLC52A2 Achchuthan Shanmugasundram Tag treatable tag was added to gene: SLC52A2.
Hereditary neuropathy or pain disorder v2.7 SLC52A2 Achchuthan Shanmugasundram Phenotypes for gene: SLC52A2 were changed from to Brown-Vialetto-Van Laere syndrome 2, MIM# 614707, MONDO:0013867; Hereditary sensory and autonomic neuropathy, MONDO:0015364
Hereditary neuropathy or pain disorder v2.6 SLC52A2 Achchuthan Shanmugasundram Publications for gene: SLC52A2 were set to BVVL; Brown-Vialetto-Van Laere syndrome 2
Hereditary neuropathy or pain disorder v2.5 SLC52A2 Achchuthan Shanmugasundram reviewed gene: SLC52A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22740598, 22864630, 23243084, 24253200, 30343981, 30377535, 31868069, 32909658, 35608644, 36186484; Phenotypes: Brown-Vialetto-Van Laere syndrome 2, MIM# 614707, MONDO:0013867, Hereditary sensory and autonomic neuropathy, MONDO:0015364, Progressive bulbar palsy, MONDO:0008890; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v3.14 SLC52A2 Achchuthan Shanmugasundram Tag treatable tag was added to gene: SLC52A2.
Tag Q4_22_promote_green tag was added to gene: SLC52A2.
Paediatric motor neuronopathies v2.3 SLC52A2 Achchuthan Shanmugasundram Publications for gene: SLC52A2 were set to 23243084; 22864630
Paediatric motor neuronopathies v2.2 SLC52A2 Achchuthan Shanmugasundram Phenotypes for gene: SLC52A2 were changed from Brown-Vialetto-Van Laere syndrome 2, OMIM:614707 to Brown-Vialetto-Van Laere syndrome 2, MIM# 614707, MONDO:0013867; Hereditary sensory and autonomic neuropathy, MONDO:0015364
Paediatric motor neuronopathies v2.1 SLC52A2 Achchuthan Shanmugasundram reviewed gene: SLC52A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22740598, 22864630, 23243084, 24253200, 30343981, 30377535, 31868069, 32909658, 35608644, 36186484; Phenotypes: Brown-Vialetto-Van Laere syndrome 2, MIM# 614707, MONDO:0013867, Hereditary sensory and autonomic neuropathy, MONDO:0015364, Progressive bulbar palsy, MONDO:0008890; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v3.14 SLC52A2 Achchuthan Shanmugasundram Phenotypes for gene: SLC52A2 were changed from Brown-Vialetto-Van Laere syndrome 2, MIM# 614707 to Brown-Vialetto-Van Laere syndrome 2, MIM# 614707, MONDO:0013867; Cerebellar ataxia, MONDO:0000437
Ataxia and cerebellar anomalies - narrow panel v3.13 SLC52A2 Achchuthan Shanmugasundram Publications for gene: SLC52A2 were set to 30377535
Ataxia and cerebellar anomalies - narrow panel v3.12 SLC52A2 Achchuthan Shanmugasundram Classified gene: SLC52A2 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v3.12 SLC52A2 Achchuthan Shanmugasundram Gene: slc52a2 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v3.11 SLC52A2 Achchuthan Shanmugasundram reviewed gene: SLC52A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 22740598, 22864630, 23243084, 24253200, 30343981, 30377535, 31868069, 32909658, 35608644, 36186484; Phenotypes: Brown-Vialetto-Van Laere syndrome 2, MIM# 614707, MONDO:0013867, Cerebellar ataxia, MONDO:0000437; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v2.5 SLC25A46 Achchuthan Shanmugasundram Tag Q4_22_promote_green tag was added to gene: SLC25A46.
Hereditary neuropathy or pain disorder v2.5 SLC25A46 Achchuthan Shanmugasundram Phenotypes for gene: SLC25A46 were changed from Neuropathy, hereditary motor and sensory, type VIB, 616505; Optic atrophy and progressive visual loss in the 1st decade, then spasticity, cerebellar ataxia, sensory-motor axonal neuropathy to Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505; Pontocerebellar hypoplasia, type 1E, MIM# 619303, MONDO:0030260
Hereditary neuropathy or pain disorder v2.4 SLC25A46 Achchuthan Shanmugasundram Publications for gene: SLC25A46 were set to 26168012
Hereditary neuropathy or pain disorder v2.3 SLC25A46 Achchuthan Shanmugasundram reviewed gene: SLC25A46: Rating: GREEN; Mode of pathogenicity: None; Publications: 26168012, 27430653, 28376086, 28934388, 30178502; Phenotypes: Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505, Pontocerebellar hypoplasia, type 1E, MIM# 619303, MONDO:0030260; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v3.3 SLC25A46 Achchuthan Shanmugasundram Phenotypes for gene: SLC25A46 were changed from Neuropathy, hereditary motor and sensory, type VIB 616505 to Optic atrophy, MONDO:0003608; Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505; Pontocerebellar hypoplasia, type 1E, MIM# 619303, MONDO:0030260
Optic neuropathy v3.2 SLC25A46 Achchuthan Shanmugasundram Publications for gene: SLC25A46 were set to 26168012; 28369803
Optic neuropathy v3.1 SLC25A46 Achchuthan Shanmugasundram reviewed gene: SLC25A46: Rating: GREEN; Mode of pathogenicity: None; Publications: 26168012, 27430653, 28369803, 28376086, 28558379, 28934388, 30178502, 33816684; Phenotypes: Optic atrophy, MONDO:0003608, Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505, Pontocerebellar hypoplasia, type 1E, MIM# 619303, MONDO:0030260; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v3.5 SLC25A46 Achchuthan Shanmugasundram Phenotypes for gene: SLC25A46 were changed from Hereditary motor and sensory neuropathy type VIB, 616505 to Cerebellar ataxia, MONDO:0000437; Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505
Hereditary ataxia with onset in adulthood v3.4 SLC25A46 Achchuthan Shanmugasundram Publications for gene: SLC25A46 were set to
Hereditary ataxia with onset in adulthood v3.3 SLC25A46 Achchuthan Shanmugasundram reviewed gene: SLC25A46: Rating: GREEN; Mode of pathogenicity: None; Publications: 26168012, 28376086, 28558379, 28934388; Phenotypes: Adult-onset ataxia, Cerebellar ataxia, MONDO:0000437, Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v3.11 SLC25A46 Achchuthan Shanmugasundram changed review comment from: Comment on classification of this gene: The rating for this gene should be GREEN, as this gene has been implicated in ataxia, as identified from biallelic loss-of-function variants from at least 8 unrelated individuals/ families from multiple ethnicities and supported by results from animal models.

Two brothers of consanguineous parents of Pakistani origin were identified with homozygous variant in SLC25A46 (c.413T>G./ p.Leu138Arg). The younger of the two brothers was presented with balancing difficulties in infancy, prominent myoclonus, cerebellar ataxia, profound visual loss, rod cone dysfunction, exotropia, difficulty initiating saccades, mild spasticity, and axonal sensory-motor neuropathy leading to trophic changes. He also developed scoliosis and had cerebellar atrophy as well as T2/FLAIR (fluid-attenuated inversion recovery) hyperintensities and cavitations in the cerebellum. The older brother was mildly affected with similar clinical manifestations (PMID:27430653).

A study on patients from three North African families (Two siblings from Tunisian family and two unrelated Algerians) showed that the previously reported variant c.1018C>T/ p.Arg340Cys (displayed in Tunisian siblings and one Algerian patient) was associated with childhood onset, optic atrophy, gait and speech difficulties and wasting of the lower limbs, and the Algerian patient with the novel variant p.Trp160Ser did not present with optic atrophy, while all patients were presented with ataxia (PMID:28558379). Similarly, ataxia was also observed in Sardinian (p.Arg340Cys) and Palestinian (c.1005A>T/ p.Glu335Asp) patients from Abrams et al, 2015 (PMID:26168012).

A six year old boy with homozygous missense variant c.770G>A (p.Arg257Gln) was reported with optic atrophy, peripheral neuropathy, ataxia, but not cerebellar atrophy (PMID:30178502). p.Arg340Cys variant was also identified in the eleven year old male patient and in other unaffected family members, and the patient was presented with insidious onset, progressive vision loss and swaying since 8 years of age. The other presentations were gait ataxia, torticollis to left and tilt to right, head tremors and myoclonus (PMID:33816684).

Mouse models with loss-of-function mutation or lacking SLC25A46 gene manifest the main clinical features identified in patients such as ataxia, optic atrophy, cerebellar hypoplasia and peripheral neuropathy which were completely rescued by expression of human ortholog (PMID:28376086; PMID:28934388). The results suggest that the gene loss causes degeneration in neurons by affecting mitochondrial dynamics and energy production.

Loss-of-function in cultured cells and in zebrafish also led to increased mitochondrial connectivity, while severely affecting the development and maintenance of neurons in the zebrafish (PMID:26168012).

SLC25A46 has been associated with neuropathy, hereditary motor and sensory, type VIB in OMIM and Gene2Phenotype and with pontocerebellar hypoplasia, type 1E in OMIM.; to: Comment on classification of this gene:

The rating for this gene should be GREEN, as this gene has been identified to be implicated in cerebellar ataxia (MONDO:0000437) from biallelic loss-of-function variants from at least 8 unrelated individuals/ families and in pontocerebellar hypoplasia, type 1E (MIM# 619303) from biallelic loss-of-function variants from at least 6 unrelated individuals/ families. These cases were from multiple ethnicities and were supported by results from animal models.

In addition, this gene has also been identified to be implicated in cerebellar hypoplasia from monoallelic loss-of-function variants from a family of three siblings. As we currently do not have three unrelated cases for monoallelic inheritance, this gene is assigned only to biallelic MOI.

Cerebellar ataxia:

Two brothers of consanguineous parents of Pakistani origin were identified with homozygous variant in SLC25A46 (c.413T>G./ p.Leu138Arg). The younger of the two brothers was presented with balancing difficulties in infancy, prominent myoclonus, cerebellar ataxia, profound visual loss, rod cone dysfunction, exotropia, difficulty initiating saccades, mild spasticity, and axonal sensory-motor neuropathy leading to trophic changes. He also developed scoliosis and had cerebellar atrophy as well as T2/FLAIR (fluid-attenuated inversion recovery) hyperintensities and cavitations in the cerebellum. The older brother was mildly affected with similar clinical manifestations (PMID:27430653).

A study on patients from three North African families (Two siblings from Tunisian family and two unrelated Algerians) showed that the previously reported variant c.1018C>T/ p.Arg340Cys (displayed in Tunisian siblings and one Algerian patient) was associated with childhood onset, optic atrophy, gait and speech difficulties and wasting of the lower limbs, and the Algerian patient with the novel variant p.Trp160Ser did not present with optic atrophy, while all patients were presented with ataxia (PMID:28558379). Similarly, ataxia was also observed in Sardinian (p.Arg340Cys) and Palestinian (c.1005A>T/ p.Glu335Asp) patients from Abrams et al, 2015 (PMID:26168012).

A six year old boy with homozygous missense variant c.770G>A (p.Arg257Gln) was reported with optic atrophy, peripheral neuropathy, ataxia, but not cerebellar atrophy (PMID:30178502). p.Arg340Cys variant was also identified in the eleven year old male patient and in other unaffected family members, and the patient was presented with insidious onset, progressive vision loss and swaying since 8 years of age. The other presentations were gait ataxia, torticollis to left and tilt to right, head tremors and myoclonus (PMID:33816684).

Cerebellar hypoplasia:

Four infants from two different families with homozygous variants (family 1: c.1022T>C/ p.Leu341Pro; family 2: deletion of exon 1) were reported to have died soon after birth with a profound neurodevelopmental disorder associated with congenital pontocerebellar hypoplasia (PMID:27543974). The phenotypes are similar to a female infant from the United States with pontocerebellar atrophy who died at age 15 weeks. This infant reported by Abram et al (2015) exhibited compound heterozygous variants (c.882_885dupTTAC/ p.Asn296fs*297 & c.998C>T/ p.Pro333Leu) (PMID:26168012).

Four infants from two unrelated families of German and Italian descent were reported with PCH1E. All died in the first days or weeks of life. The German infants were identified with homozygous variant c.736A>T (p.Arg246Ter) and the Italian infants were identified with compound heterozygous variants c.42C>G (p.Tyr14Ter) & 462+ 1G>A (PMID:28653766).

Two siblings with bi-allelic compound heterozygous variants (a splicing variant - c.385-1G > A and a deletion) had a fulminant neonatal course. The mother of these siblings exhibited a heterozygous c.385-1G > A allele and the father had an 80-kb deletion spanning SLC25A46 and TMEM232 genes. Pontocerebellar hypoplasia was reported by postmortem brain CT imaging in one of the siblings (PMID:35012485).

Barth (1993) reported a Dutch family in which three siblings died within the first day of life due to lack of spontaneous respiration and profound muscle weakness (PMID:8147499). Although these infants displayed similarities to the clinical indications described by Wan et al, 2016 (PMID:27543974), they were identified to possess heterozygous variant leading to a premature stop codon (c.691C>T/ p.Arg231Ter) in exon 8 of the SLC25A46 gene (PMID:28637197).

Functional studies:

Mouse models with loss-of-function mutation or lacking SLC25A46 gene manifest the main clinical features identified in patients such as ataxia, optic atrophy, cerebellar hypoplasia and peripheral neuropathy which were completely rescued by expression of human ortholog (PMID:28376086; PMID:28934388). The results suggest that the gene loss causes degeneration in neurons by affecting mitochondrial dynamics and energy production.

Loss-of-function in cultured cells and in zebrafish also led to increased mitochondrial connectivity, while severely affecting the development and maintenance of neurons in the zebrafish (PMID:26168012).

SLC25A46 has been associated with neuropathy, hereditary motor and sensory, type VIB in OMIM and Gene2Phenotype and with pontocerebellar hypoplasia, type 1E in OMIM.
Ataxia and cerebellar anomalies - narrow panel v3.11 SLC25A46 Achchuthan Shanmugasundram Tag Q4_22_promote_green tag was added to gene: SLC25A46.
Ataxia and cerebellar anomalies - narrow panel v3.11 SLC25A46 Achchuthan Shanmugasundram Phenotypes for gene: SLC25A46 were changed from Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505 to Cerebellar ataxia, MONDO:0000437; Pontocerebellar hypoplasia, type 1E, MIM# 619303, MONDO:0030260; Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505
Ataxia and cerebellar anomalies - narrow panel v3.10 SLC25A46 Achchuthan Shanmugasundram Classified gene: SLC25A46 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v3.10 SLC25A46 Achchuthan Shanmugasundram Gene: slc25a46 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v3.9 SLC25A46 Achchuthan Shanmugasundram reviewed gene: SLC25A46: Rating: GREEN; Mode of pathogenicity: None; Publications: 26168012, 27430653, 28376086, 28558379, 28934388, 30178502, 33816684; Phenotypes: Cerebellar ataxia, MONDO:0000437, Pontocerebellar hypoplasia, type 1E, MIM# 619303, MONDO:0030260, Neuropathy, hereditary motor and sensory, type VIB, MIM# 616505; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v3.9 SCN2A Achchuthan Shanmugasundram Tag Q4_22_promote_green tag was added to gene: SCN2A.
Ataxia and cerebellar anomalies - narrow panel v3.9 SCN2A Achchuthan Shanmugasundram Phenotypes for gene: SCN2A were changed from Epileptic encephalopathy, early infantile, 11, MIM# 613721 to Episodic ataxia, type 9, MIM# 618924, MONDO:0030064; Developmental and epileptic encephalopathy 11, MIM# 613721, MONDO:0013388
Ataxia and cerebellar anomalies - narrow panel v3.8 SCN2A Achchuthan Shanmugasundram Publications for gene: SCN2A were set to 31924505; 32893078; 31904126
Ataxia and cerebellar anomalies - narrow panel v3.7 SCN2A Achchuthan Shanmugasundram Mode of pathogenicity for gene: SCN2A was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Ataxia and cerebellar anomalies - narrow panel v3.6 SCN2A Achchuthan Shanmugasundram Classified gene: SCN2A as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v3.6 SCN2A Achchuthan Shanmugasundram Gene: scn2a has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v3.5 SCN2A Achchuthan Shanmugasundram reviewed gene: SCN2A: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 20956790, 26291284, 26645390, 27159988, 27328862, 28065826, 30165711, 30741786, 30813219, 30928199, 32893078, 35219921; Phenotypes: Episodic ataxia, type 9, MIM# 618924, MONDO:0030064, Developmental and epileptic encephalopathy 11, MIM# 613721, MONDO:0013388; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset hereditary spastic paraplegia v2.3 COQ4 Achchuthan Shanmugasundram Tag Q4_22_promote_green tag was added to gene: COQ4.
Adult onset hereditary spastic paraplegia v2.3 COQ4 Achchuthan Shanmugasundram Classified gene: COQ4 as Amber List (moderate evidence)
Adult onset hereditary spastic paraplegia v2.3 COQ4 Achchuthan Shanmugasundram Gene: coq4 has been classified as Amber List (Moderate Evidence).
Adult onset hereditary spastic paraplegia v2.2 COQ4 Achchuthan Shanmugasundram gene: COQ4 was added
gene: COQ4 was added to Hereditary spastic paraplegia - adult onset. Sources: Literature
Mode of inheritance for gene: COQ4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ4 were set to 36047608
Phenotypes for gene: COQ4 were set to Adult-onset ataxia-spasticity spectrum disease; Hereditary spastic paraparesis, MONDO:0019064; Cerebellar ataxia, MONDO:0000437
Review for gene: COQ4 was set to GREEN
Added comment: Comment on classification of this gene: The rating for this gene should be added as GREEN, as this gene has been implicated in adult onset hereditary spastic paraplegia, as identified from biallelic variants from three unrelated individuals.

Six patients from four families with bi-allelic variants were reported with adult-Onset ataxia-spasticity spectrum phenotype. Out of these, three patients (c.305G>A & c.473G>A, c.434G>A & c.437T>G, c.376G>A & c.473G>A) were identified with hereditary spastic paraparesis and their age of onset ranged from 15 to 24 (PMID:36047608).

COQ4 was not associated with hereditary spastic paraparesis in OMIM or Gene2Phenotype. However, functional studies performed in patient-derived fibroblasts, yeasts and zebrafish larvae confirms the role of COQ4 in brain development. The coq4 F0 CRISPR zebrafish line particularly showed motor defects and cell reduction in a specific area of the hindbrain, a region reminiscent of the human cerebellum (PMID:33704555).
Sources: Literature
Hereditary ataxia with onset in adulthood v3.3 COQ4 Achchuthan Shanmugasundram Tag Q4_22_promote_green tag was added to gene: COQ4.
Hereditary ataxia with onset in adulthood v3.3 COQ4 Achchuthan Shanmugasundram Classified gene: COQ4 as Amber List (moderate evidence)
Hereditary ataxia with onset in adulthood v3.3 COQ4 Achchuthan Shanmugasundram Gene: coq4 has been classified as Amber List (Moderate Evidence).
Hereditary ataxia with onset in adulthood v3.2 COQ4 Achchuthan Shanmugasundram gene: COQ4 was added
gene: COQ4 was added to Hereditary ataxia - adult onset. Sources: Literature
Mode of inheritance for gene: COQ4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ4 were set to 36047608
Phenotypes for gene: COQ4 were set to Adult-onset ataxia-spasticity spectrum disease; Hereditary spastic paraparesis, MONDO:0019064; Cerebellar ataxia, MONDO:0000437
Review for gene: COQ4 was set to GREEN
Added comment: Comment on classification of this gene: The rating for this gene should be added as GREEN, as this gene has been implicated in adult-onset ataxia, as identified from biallelic variants from three unrelated individuals/ families.

Six patients from four families with bi-allelic variants were reported with adult-Onset ataxia-spasticity spectrum phenotype. Out of these, five patients from three families with bi-allelic variants (c.305G>A & c.473G>A, c.434G>A & c.437T>G, c.202+4A>C & c.202+4A>C) were identified with gait and/or limb ataxia. The severity of the phenotype ranged from mild (c.305G>A & c.473G>A) to more severe (c.202+4A>C & c.202+4A>C ) and the age of onset ranged from 15 to 34 (PMID:36047608).

COQ4 was not associated with adult-onset ataxia-spasticity spectrum disease in OMIM or Gene2Phenotype. However, functional studies performed in patient-derived fibroblasts, yeasts and zebrafish larvae confirms the role of COQ4 in brain development. The coq4 F0 CRISPR zebrafish line particularly showed motor defects and cell reduction in a specific area of the hindbrain, a region reminiscent of the human cerebellum (PMID:33704555).
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v3.5 COQ4 Achchuthan Shanmugasundram Tag treatable tag was added to gene: COQ4.
Tag Q4_22_promote_green tag was added to gene: COQ4.
Ataxia and cerebellar anomalies - narrow panel v3.5 COQ4 Achchuthan Shanmugasundram Phenotypes for gene: COQ4 were changed from Childhood onset ataxia to Childhood-onset spinocerebellar ataxia; Adult-onset ataxia-spasticity spectrum disease; Hereditary spastic paraparesis, MONDO:0019064; Cerebellar ataxia, MONDO:0000437
Ataxia and cerebellar anomalies - narrow panel v3.4 COQ4 Achchuthan Shanmugasundram Publications for gene: COQ4 were set to PMID: 30225196; 33704555; 30847826
Ataxia and cerebellar anomalies - narrow panel v3.3 COQ4 Achchuthan Shanmugasundram Classified gene: COQ4 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v3.3 COQ4 Achchuthan Shanmugasundram Gene: coq4 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v3.2 COQ4 Achchuthan Shanmugasundram reviewed gene: COQ4: Rating: GREEN; Mode of pathogenicity: None; Publications: 30225196, 30847826, 33215859, 33704555, 36047608; Phenotypes: Childhood-onset spinocerebellar ataxia, Adult-onset ataxia-spasticity spectrum disease, Hereditary spastic paraparesis, MONDO:0019064, Cerebellar ataxia, MONDO:0000437; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ectodermal dysplasia v2.3 SREBF1 Achchuthan Shanmugasundram Tag Q4_22_promote_green tag was added to gene: SREBF1.
Ectodermal dysplasia v2.3 SREBF1 Achchuthan Shanmugasundram Classified gene: SREBF1 as Amber List (moderate evidence)
Ectodermal dysplasia v2.3 SREBF1 Achchuthan Shanmugasundram Gene: srebf1 has been classified as Amber List (Moderate Evidence).
Ectodermal dysplasia v2.2 SREBF1 Achchuthan Shanmugasundram gene: SREBF1 was added
gene: SREBF1 was added to Ectodermal dysplasia. Sources: Literature
Mode of inheritance for gene: SREBF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SREBF1 were set to 31790666; 32497488; 32902915; 33253727; 33742461
Phenotypes for gene: SREBF1 were set to Ichthyosis, follicular, with atrichia and photophobia syndrome 2, MIM# 619016, MONDO:0100221; Mucoepithelial dysplasia, hereditary, MIM# 158310, MONDO:0008017
Review for gene: SREBF1 was set to GREEN
Added comment: Comment on classification of this gene: The rating for this gene should be added as GREEN, as this gene has been implicated in both hereditary hair and skin conditions, as identified from monoallelic variants from at least 18 unrelated individuals/ families from multiple ethnicities, and supported by results from in vitro functional studies.

As reviewed by Zornitza Stark, heterozygous variants in 11 unrelated, ethnically diverse individuals has resulted in IFAP syndrome (MIM# 619016), which is characterised generally by moderate or severe hypotrichosis or atrichia (hair), ichthyosis follicularis (skin), and photophobia, Meibomian gland dysfunction, keratitis and/or cataract (eye) (PMID:32497488). Similarly, autosomal-dominant IFAP syndrome was also observed in another report of a Japanese woman and her daughter displaying heterozygous variant c.1669C>T (p.Arg557Cys) in SREBF1 gene (PMID:33253727).

Seven patients from four families displaying heterozygous variants of SREBF1 gene (c.1669C>T (p.Arg557Cys) and c.1670G>A (p.Arg557His)) were reported with HMD (MIM# 158310), which is characterised by chronic keratitis, non-scarring alopecia, mucosal erythema, keratosis pilaris, perineal erythematous intertrigo, psoriatic-like perineal plaques, and involvement of the conjunctival mucosa (PMID:31790666). There are also two other reports of patients with c.1669C>T (p.Arg557Cys) variant displaying autosomal-dominant HMD (PMID:32902915, PMID:33742461). The clinical indications of IFAP and HMD suggests that these two diseases share a common clinical spectrum.

The association of both IFAP and HMD to SREBF1 has been documented in OMIM. In addition, results from in vitro investigation of SREBP1 variants confirms the essential role of SREBF1 in epidermal differentiation, skin barrier formation, hair growth, and eye function (PMID:32497488).
Sources: Literature
Ichthyosis and erythrokeratoderma v2.10 SREBF1 Achchuthan Shanmugasundram Tag Q4_22_promote_green tag was added to gene: SREBF1.
Ichthyosis and erythrokeratoderma v2.10 SREBF1 Achchuthan Shanmugasundram Phenotypes for gene: SREBF1 were changed from IFAP (ichthyosis follicularis, atrichia, and photophobia) syndrome to Ichthyosis, follicular, with atrichia and photophobia syndrome 2, MIM# 619016, MONDO:0100221; Hereditary mucoepithelial dysplasia, MIM# 158310, MONDO:0008017
Ichthyosis and erythrokeratoderma v2.9 SREBF1 Achchuthan Shanmugasundram Publications for gene: SREBF1 were set to 32497488
Ichthyosis and erythrokeratoderma v2.8 SREBF1 Achchuthan Shanmugasundram Classified gene: SREBF1 as Amber List (moderate evidence)
Ichthyosis and erythrokeratoderma v2.8 SREBF1 Achchuthan Shanmugasundram Gene: srebf1 has been classified as Amber List (Moderate Evidence).
Ichthyosis and erythrokeratoderma v2.7 SREBF1 Achchuthan Shanmugasundram reviewed gene: SREBF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31790666, 32497488, 32902915, 33253727, 33742461; Phenotypes: Ichthyosis, follicular, with atrichia and photophobia syndrome 2, MIM# 619016, MONDO:0100221, Hereditary mucoepithelial dysplasia, MIM# 158310, MONDO:0008017; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Palmoplantar keratodermas v2.4 PERP Achchuthan Shanmugasundram Tag Q4_22_promote_green tag was added to gene: PERP.
Palmoplantar keratodermas v2.4 PERP Achchuthan Shanmugasundram Phenotypes for gene: PERP were changed from Dominant and Recessive Keratoderma to Olmsted syndrome-2, MIM# 619208, MONDO:003091; Erythrokeratodermia variabilis et progressiva-7, MIM# 619209, MONDO:0030941; Ichthyosis, MONDO:0019269
Palmoplantar keratodermas v2.3 PERP Achchuthan Shanmugasundram Publications for gene: PERP were set to 30321533
Palmoplantar keratodermas v2.2 PERP Achchuthan Shanmugasundram Classified gene: PERP as Amber List (moderate evidence)
Palmoplantar keratodermas v2.2 PERP Achchuthan Shanmugasundram Gene: perp has been classified as Amber List (Moderate Evidence).
Palmoplantar keratodermas v2.1 PERP Achchuthan Shanmugasundram reviewed gene: PERP: Rating: GREEN; Mode of pathogenicity: None; Publications: 31898316, 30321533, 31361044, 34265120, 34863005, 32593191; Phenotypes: Olmsted syndrome-2, MIM# 619208, MONDO:003091, Erythrokeratodermia variabilis et progressiva-7, MIM# 619209, MONDO:0030941, Ichthyosis, MONDO:0019269, Alopecia universalis, Congenital hypotrichosis; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ichthyosis and erythrokeratoderma v2.7 PERP Achchuthan Shanmugasundram edited their review of gene: PERP: Changed phenotypes to: Olmsted syndrome-2, MIM# 619208, MONDO:003091, Erythrokeratodermia variabilis et progressiva-7, MIM# 619209, MONDO:0030941, Ichthyosis, MONDO:0019269, Alopecia universalis, congenital hypotrichosis
Ichthyosis and erythrokeratoderma v2.7 PERP Achchuthan Shanmugasundram Phenotypes for gene: PERP were changed from Olmsted syndrome-2, MIM# 619208, MONDO:003091; Erythrokeratodermia variabilis et progressiva-7, MIM# 619209, MONDO:0030941; ichthyosis, MONDO:0019269 to Olmsted syndrome-2, MIM# 619208, MONDO:003091; Erythrokeratodermia variabilis et progressiva-7, MIM# 619209, MONDO:0030941; Ichthyosis, MONDO:0019269
Ichthyosis and erythrokeratoderma v2.6 PERP Achchuthan Shanmugasundram Phenotypes for gene: PERP were changed from Olmsted syndrome-2, MIM# 619208, MONDO_003091; Erythrokeratodermia variabilis et progressiva-7, MIM# 619209, MONDO_0030941; ichthyosis, MONDO:0019269 to Olmsted syndrome-2, MIM# 619208, MONDO:003091; Erythrokeratodermia variabilis et progressiva-7, MIM# 619209, MONDO:0030941; ichthyosis, MONDO:0019269
Hereditary neuropathy or pain disorder v2.3 CADM3 Arina Puzriakova Classified gene: CADM3 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v2.3 CADM3 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). To date only one paper reports three families with the same missense variant in CADM3. A separate report and/or another variant causing disease would help corroborate this association and so rating Amber for now with a 'watchlist' tag.
Hereditary neuropathy or pain disorder v2.3 CADM3 Arina Puzriakova Gene: cadm3 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v2.2 CADM3 Arina Puzriakova Tag watchlist tag was added to gene: CADM3.
Ichthyosis and erythrokeratoderma v2.5 PERP Achchuthan Shanmugasundram Tag Q4_22_promote_green tag was added to gene: PERP.
Ichthyosis and erythrokeratoderma v2.5 PERP Achchuthan Shanmugasundram Phenotypes for gene: PERP were changed from Erythrokeratoderma, no OMIM # yet to Olmsted syndrome-2, MIM# 619208, MONDO_003091; Erythrokeratodermia variabilis et progressiva-7, MIM# 619209, MONDO_0030941; ichthyosis, MONDO:0019269
Ichthyosis and erythrokeratoderma v2.4 PERP Achchuthan Shanmugasundram Publications for gene: PERP were set to 31898316
Ichthyosis and erythrokeratoderma v2.3 PERP Achchuthan Shanmugasundram Mode of inheritance for gene: PERP was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ichthyosis and erythrokeratoderma v2.2 PERP Achchuthan Shanmugasundram Classified gene: PERP as Amber List (moderate evidence)
Ichthyosis and erythrokeratoderma v2.2 PERP Achchuthan Shanmugasundram Gene: perp has been classified as Amber List (Moderate Evidence).
Ichthyosis and erythrokeratoderma v2.1 PERP Achchuthan Shanmugasundram reviewed gene: PERP: Rating: GREEN; Mode of pathogenicity: None; Publications: 31898316, 30321533, 31361044, 34265120, 34863005, 32593191; Phenotypes: Olmsted syndrome-2, MIM# 619208, MONDO_003091, Erythrokeratodermia variabilis et progressiva-7, MIM# 619209, MONDO_0030941, ichthyosis, MONDO:0019269, Alopecia universalis, congenital hypotrichosis; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v2.2 CADM3 Arina Puzriakova Phenotypes for gene: CADM3 were changed from Charcot-Marie-Tooth disease to Charcot-Marie-Tooth disease, axonal, type 2FF, OMIM:619519
Congenital myaesthenic syndrome v3.3 TOR1AIP1 Arina Puzriakova changed review comment from: Associated with relevant phenotype in OMIM, but currently not in Gene2Phenotype.

At least 5 individuals from 2 unrelated families reported (PMID: 33215087; 34164833) specifically with a myasthenic syndrome in association with different homozygous LoF variants in this gene (c.127delC, p.Pro43fs and c.63dupC, p.Arg22Glnfs*88, respectively). Electromyography in patients revealed decremental responses on repetitive nerve stimulation. Muscle biopsy from one proband showed the protein encoded by TOR1AIP1 was absent in myonuclei.
Knockout mice exhibited fatigable muscle weakness and also decrement on repetitive nerve stimulation. Neuromuscular junctions were enlarged and fragmented, and the number of subsynaptic nuclei was significantly increased signifying impaired synaptic transmission.; to: At least 5 individuals from 2 unrelated families reported (PMID: 33215087; 34164833) specifically with a myasthenic syndrome in association with different homozygous LoF variants in this gene (c.127delC, p.Pro43fs and c.63dupC, p.Arg22Glnfs*88, respectively). Electromyography in patients revealed decremental responses on repetitive nerve stimulation. Muscle biopsy from one proband showed the protein encoded by TOR1AIP1 was absent in myonuclei.
Knockout mice exhibited fatigable muscle weakness and also decrement on repetitive nerve stimulation. Neuromuscular junctions were enlarged and fragmented, and the number of subsynaptic nuclei was significantly increased signifying impaired synaptic transmission.
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.
-----
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
Congenital myaesthenic syndrome v3.3 TOR1AIP1 Arina Puzriakova Classified gene: TOR1AIP1 as Amber List (moderate evidence)
Congenital myaesthenic syndrome v3.3 TOR1AIP1 Arina Puzriakova Added comment: Comment on list classification: At least two unrelated multiplex families reported with muscle fatigability, limb girdle weakness and impaired transmission at the neuromuscular synapse. Given the strong functional support including a concordant mouse model, this gene can be promoted to Green status on this panel at the next GMS panel update.
Congenital myaesthenic syndrome v3.3 TOR1AIP1 Arina Puzriakova Gene: tor1aip1 has been classified as Amber List (Moderate Evidence).
Congenital myaesthenic syndrome v3.2 TOR1AIP1 Arina Puzriakova Tag Q4_22_promote_green tag was added to gene: TOR1AIP1.
Congenital myaesthenic syndrome v3.2 TOR1AIP1 Arina Puzriakova Publications for gene: TOR1AIP1 were set to 24856141; 31299614
Congenital myaesthenic syndrome v3.1 TOR1AIP1 Arina Puzriakova edited their review of gene: TOR1AIP1: Changed publications to: 33215087, 34164833
Congenital myaesthenic syndrome v3.1 TOR1AIP1 Arina Puzriakova reviewed gene: TOR1AIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24856141, 27342937, 30723199, 31299614, 32055997; Phenotypes: Congenital myasthenic syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Osteogenesis imperfecta v3.3 SHOX Arina Puzriakova Mode of inheritance for gene: SHOX was changed from to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Fetal anomalies v2.2 SHOX Arina Puzriakova Phenotypes for gene: SHOX were changed from LANGER MESOMELIC DYSPLASIA; LERI-WEILL DYSCHONDROSTEOSIS to Langer mesomelic dysplasia, OMIM:249700 (PR); Leri-Weill dyschondrosteosis, OMIM:127300 (PD); Short stature, idiopathic familial, OMIM:300582
IUGR and IGF abnormalities v1.55 SHOX Arina Puzriakova Phenotypes for gene: SHOX were changed from to Langer mesomelic dysplasia, OMIM:249700 (PR); Leri-Weill dyschondrosteosis, OMIM:127300 (PD); Short stature, idiopathic familial, OMIM:300582
Osteogenesis imperfecta v3.2 SHOX Arina Puzriakova Phenotypes for gene: SHOX were changed from Short stature, idiopathic familial, 300582; Leri-Weill dyschondrosteosis, 127300; Langer mesomelic dysplasia, 249700; Proportionate Short Stature/Small for Gestational Age; Disproportionate Short Stature to Langer mesomelic dysplasia, OMIM:249700 (PR); Leri-Weill dyschondrosteosis, OMIM:127300 (PD); Short stature, idiopathic familial, OMIM:300582; Dorsolateral bowed, short radii; Bowing and curving of radius; Radioulnar shortening
Skeletal dysplasia v3.2 SHOX Arina Puzriakova Phenotypes for gene: SHOX were changed from Langer mesomelic dysplasia 249700; Short stature, idiopathic familial 300582; Leri-Weill dyschondrosteosis 127300 to Langer mesomelic dysplasia, OMIM:249700 (PR); Leri-Weill dyschondrosteosis, OMIM:127300 (PD); Short stature, idiopathic familial, OMIM:300582; Dorsolateral bowed, short radii; Bowing and curving of radius; Radioulnar shortening
Intellectual disability v4.4 SHOX Arina Puzriakova Phenotypes for gene: SHOX were changed from SHOX deficiency (with Intellectual disability) to Langer mesomelic dysplasia, OMIM:249700 (PR); Leri-Weill dyschondrosteosis, OMIM:127300 (PD); Short stature, idiopathic familial, OMIM:300582
Radial dysplasia v1.23 SHOX Arina Puzriakova Phenotypes for gene: SHOX were changed from Leri-Weill dyschondrosteosis, 127300; bowing of the radius; radioulnar shortening; Langer mesomelic dysplasia, 249700; curved radius; dorsolateral bowed, short radii to Langer mesomelic dysplasia, OMIM:249700 (PR); Leri-Weill dyschondrosteosis, OMIM:127300 (PD); Short stature, idiopathic familial, OMIM:300582; Dorsolateral bowed, short radii; Bowing and curving of radius; Radioulnar shortening
Limb disorders v3.3 SHOX Arina Puzriakova Phenotypes for gene: SHOX were changed from Langer mesomelic dysplasia, 249700; dorsolateral bowed, short radii; bowing of the radius; curved radius; radioulnar shortening; Leri-Weill dyschondrosteosis, 127300 to Langer mesomelic dysplasia, OMIM:249700 (PR); Leri-Weill dyschondrosteosis, OMIM:127300 (PD); Short stature, idiopathic familial, OMIM:300582; Dorsolateral bowed, short radii; Bowing and curving of radius; Radioulnar shortening
Limb disorders v3.2 SHOX Arina Puzriakova Mode of inheritance for gene: SHOX was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Intellectual disability v4.3 SHOX Arina Puzriakova Mode of inheritance for gene: SHOX was changed from Unknown to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Early onset or syndromic epilepsy v3.1 KLHL20 Dmitrijs Rots gene: KLHL20 was added
gene: KLHL20 was added to Genetic epilepsy syndromes. Sources: Literature
Mode of inheritance for gene: KLHL20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KLHL20 were set to 36214804
Phenotypes for gene: KLHL20 were set to developmental disorder with intellectual disability, epilepsy, and autism spectrum disorder
Mode of pathogenicity for gene: KLHL20 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: KLHL20 was set to GREEN
Added comment: 14 cases with mostly recurrent missense variant in this gene is reported.
Sources: Literature
Intellectual disability v4.2 KLHL20 Dmitrijs Rots gene: KLHL20 was added
gene: KLHL20 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: KLHL20 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KLHL20 were set to 36214804
Phenotypes for gene: KLHL20 were set to developmental disorder with intellectual disability, epilepsy, and autism spectrum disorder
Penetrance for gene: KLHL20 were set to unknown
Mode of pathogenicity for gene: KLHL20 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: KLHL20 was set to GREEN
Added comment: More 14 individuals with mostly recurrent missense variant reported in KLHL20
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v3.1 TBX1 Ronnie Wright reviewed gene: TBX1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.1 POGLUT1 Katherine Schon reviewed gene: POGLUT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31897643; Phenotypes: limb girdle weakness, thigh weakness, muscle MRI abnormality; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v2.1 GRM1 Zornitza Stark reviewed gene: GRM1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spinocerebellar ataxia, autosomal recessive 13 MIM#614831; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.2 PAX6 Tracy Lester reviewed gene: PAX6: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v4.2 RARB Zornitza Stark reviewed gene: RARB: Rating: GREEN; Mode of pathogenicity: None; Publications: 30880327, 30281527, 24075189, 27120018, 25457163, 17506106; Phenotypes: Microphthalmia, syndromic 12, MIM# 615524, Neurodevelopmental disorder; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Dilated Cardiomyopathy and conduction defects v1.81 PRDM16 Zornitza Stark reviewed gene: PRDM16: Rating: GREEN; Mode of pathogenicity: None; Publications: 29367541, 29447731, 30847666, 33082984, 32183154, 33500567, 34540771, 34350506, 34935411, 35862303, 32083975; Phenotypes: Cardiomyopathy, dilated, 1LL MIM#615373, Left ventricular noncompaction 8 MIM#615373; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v4.2 BLM Zornitza Stark reviewed gene: BLM: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Bloom syndrome, MIM# 210900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v4.2 PRSS12 Sarah Leigh Publications for gene: PRSS12 were set to
Adult onset neurodegenerative disorder v3.2 COG5 Arina Puzriakova Added comment: Comment on mode of inheritance: All cases reported to date have been associated with recessive inheritance with the exception of one family with "one potential heterozygous mutation" reported in 2017 (PMID: 28960046). As no further monoallelic cases have been reported since, updating the MOI from 'both mono- and biallelic' to 'biallelic' only until further evidence emerges supporting pathogenicity of heterozygous variants in this gene.
Adult onset neurodegenerative disorder v3.2 COG5 Arina Puzriakova Mode of inheritance for gene: COG5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia v1.313 COG5 Arina Puzriakova Added comment: Comment on mode of inheritance: All cases reported to date have been associated with recessive inheritance with the exception of one family with "one potential heterozygous mutation" reported in 2017 (PMID: 28960046). As no further monoallelic cases have been reported since, updating the MOI from 'both mono- and biallelic' to 'biallelic' only until further evidence emerges supporting pathogenicity of heterozygous variants in this gene.
Hereditary ataxia v1.313 COG5 Arina Puzriakova Mode of inheritance for gene: COG5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v3.2 COG5 Arina Puzriakova Mode of inheritance for gene: COG5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v3.1 COG5 Arina Puzriakova Tag watchlist_moi tag was added to gene: COG5.
Unexplained kidney failure in young people v1.116 FAN1 Yu Leng Phua reviewed gene: FAN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35931300; Phenotypes: interstitial nephritis, chronic kidney disease, Interstitial nephritis, karyomegalic 614817; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease v2.1 FAN1 Yu Leng Phua reviewed gene: FAN1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35931300; Phenotypes: interstitial nephritis, chronic kidney disease, Interstitial nephritis, karyomegalic 614817; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ectodermal dysplasia v2.1 LEF1 Yu Leng Phua reviewed gene: LEF1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35583550; Phenotypes: Radial ray defects, polydactyly, split hand/foot, ectodermal dysplasia; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hypotonic infant v18.2 Arina Puzriakova Panel version 18.1 has been signed off on 2022-11-30
Cardiac arrhythmias v11.2 Eleanor Williams Panel version 11.1 has been signed off on 2022-11-30
Childhood onset leukodystrophy v10.3 Arina Puzriakova Panel version 10.2 has been signed off on 2022-11-30
Sudden unexplained death or survivors of a cardiac event v17.4 Eleanor Williams Panel version 17.3 has been signed off on 2022-11-30
Other rare neuromuscular disorders v12.2 Arina Puzriakova Panel version 12.1 has been signed off on 2022-11-30
Rare multisystem ciliopathy Super panel v8.3 Arina Puzriakova Panel version 8.2 has been signed off on 2022-11-30
Sudden unexplained death or survivors of a cardiac event v17.3 Eleanor Williams List of related panels changed from Molecular autopsy; Sudden cardiac death; Sudden cardiac death PILOT; R138; 425 to Molecular autopsy; Sudden cardiac death; Sudden cardiac death PILOT; R138; R425
Hypogonadotropic hypogonadism (GMS) v2.3 Achchuthan Shanmugasundram Panel version 2.2 has been signed off on 2022-11-30
Cerebral malformation v8.3 Eleanor Williams Panel version 8.2 has been signed off on 2022-11-30
Hypogonadotropic hypogonadism (GMS) v2.2 Achchuthan Shanmugasundram Panel signed off version 2.0 has been removed
Paediatric disorders v24.3 Arina Puzriakova Panel version 24.2 has been signed off on 2022-11-30
Cystic renal disease v5.2 Eleanor Williams Panel version 5.1 has been signed off on 2022-11-30
Pulmonary fibrosis familial v1.4 Achchuthan Shanmugasundram Panel types changed to GMS Rare Disease; GMS signed-off
Panel version 1.3 has been signed off on 2022-11-30
Pulmonary fibrosis familial v1.3 Achchuthan Shanmugasundram Panel signed off version 1.0 has been removed
Pulmonary fibrosis familial v1.2 Achchuthan Shanmugasundram Panel signed off version 1.1 has been removed
Hereditary ataxia and cerebellar anomalies - childhood onset v9.2 Arina Puzriakova Panel version 9.1 has been signed off on 2022-11-30
Fetal anomalies v2.1 Eleanor Williams Panel version 2.0 has been signed off on 2022-11-30
Fetal anomalies v2.0 Eleanor Williams promoted panel to version 2.0
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v3.3 Eleanor Williams List of related panels changed from Familial hyperparathyroidism; Hypocalciuric hypercalcaemia; R151; R152 to Familial hyperparathyroidism; Hypocalciuric hypercalcaemia; R151
Panel version 3.2 has been signed off on 2022-11-30
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v3.2 Eleanor Williams Panel signed off version 3.0 has been removed
Auditory Neuropathy Spectrum Disorde v1.9 ATP11A Barbara Vona gene: ATP11A was added
gene: ATP11A was added to Auditory Neuropathy Spectrum Disorder. Sources: Literature
Mode of inheritance for gene: ATP11A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP11A were set to PMID: 36300302; 28601886
Phenotypes for gene: ATP11A were set to Auditory synaptopathy/neuropathy; AUNA2
Penetrance for gene: ATP11A were set to Complete
Mode of pathogenicity for gene: ATP11A was set to Other
Review for gene: ATP11A was set to RED
gene: ATP11A was marked as current diagnostic
Added comment: A large German family with auditory synaptopathy/neuropathy that originally mapped the AUNA2 locus to either chromosome 12q24 or 13q34 underwent genome sequencing. Affected individuals showed symmetrical, slowly progressive postlingual hearing loss starting late in the first decade that eventually advanced to to severe hearing impairment in the fifth decade. Auditory brainstem response thresholds were worse than otoacoustic emissions, suggesting a deficit in neural sound encoding. A 5.5 kb deletion encompassing the last coding exon of both RefSeq annotated ATP11A isoforms was found to segregate with the phenotype. RNA studies from an affected individual confirmed stable expression and both a deletion and activation of a cryptic splice acceptor that leads to inclusion of a pseudoexon and novel 38 amino acids at the C-terminus. ATP11A flippase activity was disrupted in mutant cells, compatible with a loss-of-function mechanism, although a gain of function of dominant negative effect could not be excluded. ATP11A is expressed in the mouse inner ear. Its function was explored in depth using a conditional knockout mouse that showed a progressive dysfunction or loss of spiral ganglion neurons. Additional families are needed to replicate an auditory synaptopathy/neuropathy phenotype.
Sources: Literature
Arrhythmogenic right ventricular cardiomyopathy v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2022-11-30
Arrhythmogenic right ventricular cardiomyopathy v3.0 Arina Puzriakova promoted panel to version 3.0
Severe early-onset obesity v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2022-11-30
Early onset or syndromic epilepsy v3.1 Catherine Snow Panel version 3.0 has been signed off on 2022-11-30
Early onset or syndromic epilepsy v3.0 Catherine Snow promoted panel to version 3.0
Severe early-onset obesity v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Familial melanoma v2.1 Catherine Snow Panel version 2.0 has been signed off on 2022-11-30
Familial melanoma v2.0 Catherine Snow promoted panel to version 2.0
Rare genetic inflammatory skin disorders v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2022-11-30
Cytopenia - NOT Fanconi anaemia v2.1 Catherine Snow Panel version 2.0 has been signed off on 2022-11-30
Rare genetic inflammatory skin disorders v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Cytopenia - NOT Fanconi anaemia v2.0 Catherine Snow promoted panel to version 2.0
Tubulointerstitial kidney disease v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2022-11-30
Tubulointerstitial kidney disease v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.1 Catherine Snow Panel version 2.0 has been signed off on 2022-11-30
Inherited phaeochromocytoma and paraganglioma excluding NF1 v2.0 Catherine Snow promoted panel to version 2.0
Structural eye disease v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2022-11-30
Structural eye disease v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Stickler syndrome v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2022-11-30
Endocrine neoplasia v2.1 Catherine Snow Panel version 2.0 has been signed off on 2022-11-30
Stickler syndrome v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Endocrine neoplasia v2.0 Catherine Snow promoted panel to version 2.0
Thrombophilia with a likely monogenic cause v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2022-11-30
Thrombophilia with a likely monogenic cause v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Differences in sex development v3.1 Catherine Snow Panel version 3.0 has been signed off on 2022-11-30
Thoracic aortic aneurysm or dissection (GMS) v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2022-11-30
Differences in sex development v3.0 Catherine Snow promoted panel to version 3.0
Thoracic aortic aneurysm or dissection (GMS) v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Neonatal diabetes v3.1 Catherine Snow Panel version 3.0 has been signed off on 2022-11-30
Laterality disorders and isomerism v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2022-11-30
Neonatal diabetes v3.0 Catherine Snow promoted panel to version 3.0
Laterality disorders and isomerism v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Nephrocalcinosis or nephrolithiasis v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2022-11-30
Ectodermal dysplasia v2.1 Catherine Snow Panel version 2.0 has been signed off on 2022-11-30
Nephrocalcinosis or nephrolithiasis v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Ectodermal dysplasia v2.0 Catherine Snow promoted panel to version 2.0
Acute rhabdomyolysis v1.1 Catherine Snow Panel types changed to GMS Rare Disease; GMS signed-off
Panel version 1.0 has been signed off on 2022-11-30
Acute rhabdomyolysis v1.0 Catherine Snow promoted panel to version 1.0
Paroxysmal central nervous system disorders v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2022-11-30
Autoinflammatory disorders v1.1 Catherine Snow Panel types changed to GMS Rare Disease; GMS signed-off
Panel version 1.0 has been signed off on 2022-11-30
Paroxysmal central nervous system disorders v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Autoinflammatory disorders v1.0 Catherine Snow promoted panel to version 1.0
Respiratory ciliopathies including non-CF bronchiectasis v2.1 Arina Puzriakova Panel version 2.0 has been signed off on 2022-11-30
Adult onset neurodegenerative disorder v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2022-11-30
Respiratory ciliopathies including non-CF bronchiectasis v2.0 Arina Puzriakova promoted panel to version 2.0
Pulmonary arterial hypertension v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2022-11-30
Adult onset neurodegenerative disorder v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Pulmonary arterial hypertension v3.0 Eleanor Williams promoted panel to version 3.0
Unexplained young onset end-stage renal disease v2.1 Arina Puzriakova Panel version 2.0 has been signed off on 2022-11-30
Pulmonary fibrosis familial v1.1 Catherine Snow Panel version 1.0 has been signed off on 2022-11-30
Unexplained young onset end-stage renal disease v2.0 Arina Puzriakova promoted panel to version 2.0
Pulmonary fibrosis familial v1.0 Catherine Snow promoted panel to version 1.0
Renal tubulopathies v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2022-11-30
Osteogenesis imperfecta v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2022-11-30
Corneal dystrophy v2.1 Catherine Snow Panel version 2.0 has been signed off on 2022-11-30
Renal tubulopathies v3.0 Arina Puzriakova promoted panel to version 3.0
Proteinuric renal disease v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2022-11-30
Osteogenesis imperfecta v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Corneal dystrophy v2.0 Catherine Snow promoted panel to version 2.0
Proteinuric renal disease v3.0 Eleanor Williams promoted panel to version 3.0
Retinal disorders v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2022-11-30
Possible mitochondrial disorder - nuclear genes v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2022-11-30
Retinal disorders v3.0 Arina Puzriakova promoted panel to version 3.0
Malignant hyperthermia v1.1 Catherine Snow Panel types changed to GMS Rare Disease; GMS signed-off
Panel version 1.0 has been signed off on 2022-11-30
Adult onset leukodystrophy v2.1 Eleanor Williams Panel version 2.0 has been signed off on 2022-11-30
Possible mitochondrial disorder - nuclear genes v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Adult onset leukodystrophy v2.0 Eleanor Williams promoted panel to version 2.0
Skeletal muscle channelopathy v2.1 Arina Puzriakova Panel version 2.0 has been signed off on 2022-11-30
Malignant hyperthermia v1.0 Catherine Snow promoted panel to version 1.0
Skeletal muscle channelopathy v2.0 Arina Puzriakova promoted panel to version 2.0
Rare anaemia v2.1 Eleanor Williams Panel version 2.0 has been signed off on 2022-11-30
Severe microcephaly v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2022-11-30
Rare anaemia v2.0 Eleanor Williams promoted panel to version 2.0
Severe microcephaly v3.0 Arina Puzriakova promoted panel to version 3.0
Pancreatitis v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2022-11-30
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.1 Catherine Snow Panel version 3.0 has been signed off on 2022-11-30
Bilateral congenital or childhood onset cataracts v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2022-11-30
Rare syndromic craniosynostosis or isolated multisuture synostosis v3.0 Catherine Snow promoted panel to version 3.0
Primary lymphoedema v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2022-11-30
Bilateral congenital or childhood onset cataracts v3.0 Arina Puzriakova promoted panel to version 3.0
Childhood onset dystonia, chorea or related movement disorder v2.1 Arina Puzriakova Panel version 2.0 has been signed off on 2022-11-30
Primary lymphoedema v3.0 Eleanor Williams promoted panel to version 3.0
Pancreatitis v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Childhood onset dystonia, chorea or related movement disorder v2.0 Arina Puzriakova promoted panel to version 2.0
Wilms tumour with features suggestive of predisposition v1.1 Catherine Snow Panel types changed to GMS Rare Disease; GMS signed-off
Panel version 1.0 has been signed off on 2022-11-30
Cholestasis v2.1 Arina Puzriakova Panel version 2.0 has been signed off on 2022-11-30
Pigmentary skin disorders v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2022-11-30
Childhood solid tumours v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2022-11-30
Cholestasis v2.0 Arina Puzriakova promoted panel to version 2.0
Wilms tumour with features suggestive of predisposition v1.0 Catherine Snow promoted panel to version 1.0
Pigmentary skin disorders v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Childhood solid tumours v3.0 Eleanor Williams promoted panel to version 3.0
Palmoplantar keratodermas v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2022-11-30
Congenital adrenal hypoplasia v3.1 Catherine Snow Panel version 3.0 has been signed off on 2022-11-30
Haematological malignancies cancer susceptibility v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2022-11-30
Palmoplantar keratodermas v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Congenital adrenal hypoplasia v3.0 Catherine Snow promoted panel to version 3.0
Haematological malignancies cancer susceptibility v3.0 Eleanor Williams promoted panel to version 3.0
Multiple monogenic benign skin tumours v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2022-11-30
Hereditary ataxia with onset in adulthood v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2022-11-30
Hereditary ataxia with onset in adulthood v3.0 Eleanor Williams promoted panel to version 3.0
Multiple monogenic benign skin tumours v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Inherited pancreatic cancer v2.1 Eleanor Williams Panel version 2.0 has been signed off on 2022-11-30
Mitochondrial DNA maintenance disorder v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2022-11-30
Inherited pancreatic cancer v2.0 Eleanor Williams promoted panel to version 2.0
Multi locus imprinting disorders v1.1 Catherine Snow Panel types changed to GMS Rare Disease; GMS signed-off
Panel version 1.0 has been signed off on 2022-11-30
Mitochondrial DNA maintenance disorder v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Paediatric or syndromic cardiomyopathy v2.1 Arina Puzriakova Panel version 2.0 has been signed off on 2022-11-30
Multi locus imprinting disorders v1.0 Catherine Snow promoted panel to version 1.0
Paediatric or syndromic cardiomyopathy v2.0 Arina Puzriakova promoted panel to version 2.0
Inherited predisposition to acute myeloid leukaemia (AML) v2.1 Eleanor Williams Panel version 2.0 has been signed off on 2022-11-30
Mitochondrial disorder with complex IV deficiency v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2022-11-30
Adult onset dystonia, chorea or related movement disorder v2.1 Arina Puzriakova Panel version 2.0 has been signed off on 2022-11-30
Inherited predisposition to acute myeloid leukaemia (AML) v2.0 Eleanor Williams promoted panel to version 2.0
Cutaneous photosensitivity with a likely genetic cause v2.1 Catherine Snow Panel version 2.0 has been signed off on 2022-11-30
Adult onset dystonia, chorea or related movement disorder v2.0 Arina Puzriakova promoted panel to version 2.0
Mitochondrial disorder with complex IV deficiency v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Cutaneous photosensitivity with a likely genetic cause v2.0 Catherine Snow promoted panel to version 2.0
Bardet Biedl syndrome v2.1 Arina Puzriakova Panel version 2.0 has been signed off on 2022-11-30
Hereditary haemorrhagic telangiectasia v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2022-11-30
Bardet Biedl syndrome v2.0 Arina Puzriakova promoted panel to version 2.0
Mitochondrial disorder with complex I deficiency v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2022-11-30
Hereditary haemorrhagic telangiectasia v3.0 Eleanor Williams promoted panel to version 3.0
Sporadic aniridia v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2022-11-30
Sporadic aniridia v3.0 Arina Puzriakova promoted panel to version 3.0
Mitochondrial disorder with complex I deficiency v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Childhood onset hereditary spastic paraplegia v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2022-11-30
Childhood onset hereditary spastic paraplegia v3.0 Eleanor Williams promoted panel to version 3.0
Albinism or congenital nystagmus v2.1 Arina Puzriakova Panel version 2.0 has been signed off on 2022-11-30
Inherited breast cancer and ovarian cancer v1.1 Catherine Snow Panel types changed to GMS Rare Disease; GMS signed-off
Panel version 1.0 has been signed off on 2022-11-30
Albinism or congenital nystagmus v2.0 Arina Puzriakova promoted panel to version 2.0
Arthrogryposis v4.1 Arina Puzriakova Panel version 4.0 has been signed off on 2022-11-30
Adult onset hereditary spastic paraplegia v2.1 Eleanor Williams Panel version 2.0 has been signed off on 2022-11-30
Inherited breast cancer and ovarian cancer v1.0 Catherine Snow promoted panel to version 1.0
Adult onset hereditary spastic paraplegia v2.0 Eleanor Williams promoted panel to version 2.0
Arthrogryposis v4.0 Arina Puzriakova promoted panel to version 4.0
Bleeding and platelet disorders v2.1 Arina Puzriakova Panel version 2.0 has been signed off on 2022-11-30
Hypophosphataemia or rickets v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2022-11-30
Bleeding and platelet disorders v2.0 Arina Puzriakova promoted panel to version 2.0
Short QT syndrome v3.1 Catherine Snow Panel version 3.0 has been signed off on 2022-11-30
Hypophosphataemia or rickets v3.0 Eleanor Williams promoted panel to version 3.0
Short QT syndrome v3.0 Catherine Snow promoted panel to version 3.0
Hypogonadotropic hypogonadism (GMS) v2.1 Eleanor Williams Panel version 2.0 has been signed off on 2022-11-30
Hypogonadotropic hypogonadism (GMS) v2.0 Eleanor Williams promoted panel to version 2.0
Lysosomal storage disorder v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2022-11-30
Catecholaminergic polymorphic VT v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2022-11-30
Lysosomal storage disorder v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Catecholaminergic polymorphic VT v3.0 Arina Puzriakova promoted panel to version 3.0
Hyperthyroidism v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2022-11-30
Hyperthyroidism v3.0 Eleanor Williams promoted panel to version 3.0
Brugada syndrome and cardiac sodium channel disease v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2022-11-30
Familial chylomicronaemia syndrome (FCS) v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2022-11-30
Brugada syndrome and cardiac sodium channel disease v3.0 Arina Puzriakova promoted panel to version 3.0
Familial chylomicronaemia syndrome (FCS) v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Ichthyosis and erythrokeratoderma v2.1 Eleanor Williams Panel version 2.0 has been signed off on 2022-11-30
Cardiac arrhythmias - additional genes v2.1 Arina Puzriakova Panel version 2.0 has been signed off on 2022-11-30
Ichthyosis and erythrokeratoderma v2.0 Eleanor Williams promoted panel to version 2.0
Cardiac arrhythmias - additional genes v2.0 Arina Puzriakova promoted panel to version 2.0
Lipodystrophy - childhood onset v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2022-11-30
Inherited ovarian cancer (without breast cancer) v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2022-11-30
Ataxia and cerebellar anomalies - narrow panel v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2022-11-30
Inherited ovarian cancer (without breast cancer) v3.0 Eleanor Williams promoted panel to version 3.0
Ataxia and cerebellar anomalies - narrow panel v3.0 Arina Puzriakova promoted panel to version 3.0
Lipodystrophy - childhood onset v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Progressive cardiac conduction disease v2.1 Catherine Snow Panel version 2.0 has been signed off on 2022-11-30
Clefting v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2022-11-30
Progressive cardiac conduction disease v2.0 Catherine Snow promoted panel to version 2.0
Mosaic skin disorders - deep sequencing v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2022-11-30
Clefting v3.0 Arina Puzriakova promoted panel to version 3.0
Congenital myaesthenic syndrome v3.1 Catherine Snow Panel version 3.0 has been signed off on 2022-11-30
Holoprosencephaly - NOT chromosomal v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2022-11-30
Mosaic skin disorders - deep sequencing v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Holoprosencephaly - NOT chromosomal v3.0 Eleanor Williams promoted panel to version 3.0
Congenital myaesthenic syndrome v3.0 Catherine Snow promoted panel to version 3.0
Likely inborn error of metabolism v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2022-11-30
Dilated and arrhythmogenic cardiomyopathy v2.1 Catherine Snow Panel version 2.0 has been signed off on 2022-11-30
Likely inborn error of metabolism v3.0 Eleanor Williams promoted panel to version 3.0
Dilated and arrhythmogenic cardiomyopathy v2.0 Catherine Snow promoted panel to version 2.0
Paediatric motor neuronopathies v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2022-11-30
Paediatric motor neuronopathies v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Neurological segmental overgrowth v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2022-11-30
Renal ciliopathies v2.1 Catherine Snow Panel version 2.0 has been signed off on 2022-11-30
Neurological segmental overgrowth v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Renal ciliopathies v2.0 Catherine Snow promoted panel to version 2.0
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2022-11-30
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v3.0 Arina Puzriakova promoted panel to version 3.0
White matter disorders and cerebral calcification - narrow panel v2.1 Catherine Snow Panel version 2.0 has been signed off on 2022-11-30
Intellectual disability v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2022-11-30
Ophthalmological ciliopathies v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2022-11-30
White matter disorders and cerebral calcification - narrow panel v2.0 Catherine Snow promoted panel to version 2.0
Intellectual disability v4.0 Eleanor Williams promoted panel to version 4.0
Ophthalmological ciliopathies v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Rhabdomyolysis and metabolic muscle disorders v2.1 Catherine Snow Panel version 2.0 has been signed off on 2022-11-30
Hypertrophic cardiomyopathy v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2022-11-30
Rhabdomyolysis and metabolic muscle disorders v2.0 Catherine Snow promoted panel to version 2.0
Hypertrophic cardiomyopathy v3.0 Eleanor Williams promoted panel to version 3.0
Neurological ciliopathies v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2022-11-30
Skeletal dysplasia v3.1 Catherine Snow Panel version 3.0 has been signed off on 2022-11-30
Skeletal dysplasia v3.0 Catherine Snow promoted panel to version 3.0
Neurological ciliopathies v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Hydrocephalus v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2022-11-30
Hydrocephalus v3.0 Eleanor Williams promoted panel to version 3.0
Skeletal ciliopathies v2.1 Catherine Snow Panel version 2.0 has been signed off on 2022-11-30
Skeletal ciliopathies v2.0 Catherine Snow promoted panel to version 2.0
Familial hyperparathyroidism or hypocalciuric hypercalcaemia v2.23 Arina Puzriakova Panel name changed from Familial hyperparathyroidism to Familial hyperparathyroidism or hypocalciuric hypercalcaemia
List of related panels changed from R151 to Familial hyperparathyroidism; Hypocalciuric hypercalcaemia; R151; R152
Paediatric disorders - additional genes v2.1 Achchuthan Shanmugasundram Panel version 2.0 has been signed off on 2022-11-30
Segmental overgrowth disorders - Deep sequencing v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2022-11-30
Segmental overgrowth disorders - Deep sequencing v3.0 Eleanor Williams promoted panel to version 3.0
Paediatric disorders - additional genes v2.0 Achchuthan Shanmugasundram promoted panel to version 2.0
Segmental overgrowth disorders - Deep sequencing v2.17 Eleanor Williams Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS signed-off
Distal myopathies v2.1 Catherine Snow Panel version 2.0 has been signed off on 2022-11-30
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2022-11-30
Distal myopathies v2.0 Catherine Snow promoted panel to version 2.0
Hydrocephalus v2.133 Eleanor Williams Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS signed-off
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Cystic kidney disease v3.1 Catherine Snow Panel version 3.0 has been signed off on 2022-11-30
Cystic kidney disease v3.0 Catherine Snow promoted panel to version 3.0
Optic neuropathy v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2022-11-30
Optic neuropathy v3.0 Arina Puzriakova promoted panel to version 3.0
Optic neuropathy v2.79 Arina Puzriakova List of related panels changed from Inherited optic neuropathies; R41; R42.2 to Inherited optic neuropathies; R41
Hereditary neuropathy or pain disorder v2.1 Eleanor Williams Panel version 2.0 has been signed off on 2022-11-30
Malformations of cortical development v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2022-11-30
Hereditary neuropathy or pain disorder v2.0 Eleanor Williams promoted panel to version 2.0
Malformations of cortical development v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Hereditary neuropathy or pain disorder v1.106 Eleanor Williams List of related panels changed from R78; Hereditary neuropathy or pain disorder – NOT PMP22 copy number to R78; Hereditary neuropathy or pain disorder - NOT PMP22 copy number
Congenital myopathy v3.1 Catherine Snow Panel version 3.0 has been signed off on 2022-11-30
Inherited polyposis and early onset colorectal cancer - germline testing v2.1 Arina Puzriakova Panel version 2.0 has been signed off on 2022-11-30
Inherited polyposis and early onset colorectal cancer - germline testing v2.0 Arina Puzriakova promoted panel to version 2.0
Inherited polyposis and early onset colorectal cancer - germline testing v1.33 Arina Puzriakova Panel name changed from Inherited polyposis to Inherited polyposis and early onset colorectal cancer - germline testing
List of related panels changed from R211; R209 to Inherited polyposis; R211
Congenital myopathy v3.0 Catherine Snow promoted panel to version 3.0
Limb disorders v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2022-11-30
Leber hereditary optic neuropathy v2.1 Eleanor Williams Panel version 2.0 has been signed off on 2022-11-30
Leber hereditary optic neuropathy v2.0 Eleanor Williams promoted panel to version 2.0
Limb disorders v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Leber hereditary optic neuropathy v1.14 Eleanor Williams List of related panels changed from R42 to R42.1
Congenital muscular dystrophy v3.1 Catherine Snow Panel version 3.0 has been signed off on 2022-11-30
Congenital muscular dystrophy v3.0 Catherine Snow promoted panel to version 3.0
Mitochondrial disorders v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2022-11-30
Congenital disorders of glycosylation v3.1 Catherine Snow Panel version 3.0 has been signed off on 2022-11-30
Congenital disorders of glycosylation v3.0 Catherine Snow promoted panel to version 3.0
Monogenic hearing loss v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2022-11-30
Monogenic hearing loss v3.0 Arina Puzriakova promoted panel to version 3.0
Fetal anomalies v1.993 Eleanor Williams List of related panels changed from R21; Fetal anomalies with a likely genetic cause to R21; Fetal anomalies with a likely genetic cause; Fetal anomalies with a likely genetic cause - non urgent; R412
Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; GMS signed-off
Monogenic hearing loss v2.249 Arina Puzriakova Panel name changed from Hearing loss to Monogenic hearing loss
List of related panels changed from Congenital hearing impairment; Autosomal dominant deafness; Congenital hearing impairment (profound/severe); R67 to Hearing loss; Congenital hearing impairment; Autosomal dominant deafness; Congenital hearing impairment (profound/severe); Non-syndromic hearing loss; R67
Sudden unexplained death or survivors of a cardiac event v10.2 Eleanor Williams Panel name changed from Sudden cardiac death to Sudden unexplained death or survivors of a cardiac event
List of related panels changed from Molecular autopsy; R138; R408 to Molecular autopsy; Sudden cardiac death; Sudden cardiac death PILOT; R138; 425
DDG2P v3.1 Catherine Snow Panel version 3.0 has been signed off on 2022-11-30
Mitochondrial disorders v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
DDG2P v3.0 Catherine Snow promoted panel to version 3.0
Intestinal failure or congenital diarrhoea v2.1 Arina Puzriakova Panel version 2.0 has been signed off on 2022-11-30
Long QT syndrome v3.1 Achchuthan Shanmugasundram Panel version 3.0 has been signed off on 2022-11-30
Intestinal failure or congenital diarrhoea v2.0 Arina Puzriakova promoted panel to version 2.0
Primary immunodeficiency or monogenic inflammatory bowel disease v3.1 Eleanor Williams Panel version 3.0 has been signed off on 2022-11-30
Intestinal failure or congenital diarrhoea v1.51 Arina Puzriakova Panel name changed from Intestinal failure to Intestinal failure or congenital diarrhoea
List of related panels changed from R331 to R331; Intestinal failure
Long QT syndrome v3.0 Achchuthan Shanmugasundram promoted panel to version 3.0
Primary immunodeficiency or monogenic inflammatory bowel disease v3.0 Eleanor Williams promoted panel to version 3.0
Primary immunodeficiency or monogenic inflammatory bowel disease v2.583 Eleanor Williams Panel name changed from Primary immunodeficiency to Primary immunodeficiency or monogenic inflammatory bowel disease
List of related panels changed from Primary immunodeficiency disorders; A- or hypo-gammaglobulinaemia; Congenital neutropaenia; Agranulocytosis; Combined B and T cell defect; Inherited complement deficiency; SCID; Primary immune disorder; Primary immunodeficiency; A-gammaglobulinaemia; Agammaglobulinaemia; hypo-gammaglobulinaemia; hypogammaglobulinemia; immune deficiency syndromes; Severe combined immunodeficiency; Congenital neutopenia; Familial haemophagocytic lymphohistiocytic disorders; Familial hemophagocytic lymphohistiocytic disorders; PID; Sepsis; Disseminated non-tuberculous mycobacterial infection; R15 to Primary immunodeficiency disorders; A- or hypo-gammaglobulinaemia; Congenital neutropaenia; Agranulocytosis; Combined B and T cell defect; Inherited complement deficiency; SCID; Primary immune disorder; Primary immunodeficiency; A-gammaglobulinaemia; Agammaglobulinaemia; hypo-gammaglobulinaemia; hypogammaglobulinemia; immune deficiency syndromes; Severe combined immunodeficiency; Congenital neutopenia; Familial haemophagocytic lymphohistiocytic disorders; Familial hemophagocytic lymphohistiocytic disorders; PID; Sepsis; Disseminated non-tuberculous mycobacterial infection; Primary immunodeficiency; R15
Intellectual disability v3.1771 RARB Dmitrijs Rots reviewed gene: RARB: Rating: ; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 27120018; Phenotypes: Intellectual Disability with Progressive Motor Impairment; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v2.582 IRF7 Dmitrijs Rots edited their review of gene: IRF7: Added comment: 7 families in total reported. Enough evidence for green classification.; Changed rating: GREEN; Changed publications to: 35986347, 35670811
Primary immunodeficiency or monogenic inflammatory bowel disease v2.582 KCNA5 Inga Nartisa gene: KCNA5 was added
gene: KCNA5 was added to Primary immunodeficiency. Sources: Literature,Expert Review
Mode of inheritance for gene: KCNA5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KCNA5 were set to PMID: 35748970; PMID: 34536415
Phenotypes for gene: KCNA5 were set to autoimmunity; autoinflammation
Review for gene: KCNA5 was set to GREEN
Added comment: Sources: Literature, Expert Review
Primary immunodeficiency or monogenic inflammatory bowel disease v2.582 DIAPH1 Inga Nartisa gene: DIAPH1 was added
gene: DIAPH1 was added to Primary immunodeficiency. Sources: Expert Review,Literature
Mode of inheritance for gene: DIAPH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DIAPH1 were set to PMID: 35748970; PMID: 33662367
Phenotypes for gene: DIAPH1 were set to microcephaly; epilepsy; cortical blindness; poor lymphocyte activation and proliferation, defective B-cell maturation, and lack of naive T cells.
Review for gene: DIAPH1 was set to GREEN
Added comment: Sources: Expert Review, Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v2.582 CHUK Inga Nartisa gene: CHUK was added
gene: CHUK was added to Primary immunodeficiency. Sources: Expert Review,Literature
Mode of inheritance for gene: CHUK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CHUK were set to PMID: 35748970; PMID: 34533979
Phenotypes for gene: CHUK were set to recurrent infections; skeletal abnormalities; absent secondary lymphoid structures; reduced B cell numbers; hypogammaglobulinemia; lymphocytic infiltration of intestine and liver
Review for gene: CHUK was set to GREEN
Added comment: Sources: Expert Review, Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v2.582 COPG1 Inga Nartisa gene: COPG1 was added
gene: COPG1 was added to Primary immunodeficiency. Sources: Expert Review,Literature
Mode of inheritance for gene: COPG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COPG1 were set to PMID: 35748970; PMID: 33529166
Phenotypes for gene: COPG1 were set to persistent bacterial infection; persistent viral infections; defective humoral and cellular immunity
Review for gene: COPG1 was set to GREEN
Added comment: Sources: Expert Review, Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v2.582 MAN2B2 Inga Nartisa gene: MAN2B2 was added
gene: MAN2B2 was added to Primary immunodeficiency. Sources: Other
Mode of inheritance for gene: MAN2B2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAN2B2 were set to PMID: 31775018
Review for gene: MAN2B2 was set to GREEN
Added comment: Sources: Other
Ataxia and cerebellar anomalies - narrow panel v2.318 COG5 Arina Puzriakova Mode of inheritance for gene: COG5 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.317 COG5 Arina Puzriakova Added comment: Comment on mode of inheritance: All cases reported to date have been associated with recessive inheritance with the exception of one family with "one potential heterozygous mutation" reported in 2017 (PMID: 28960046). As no further monoallelic cases have been reported since, updating the MOI from 'both mono- and biallelic' to 'biallelic' only until further evidence emerges supporting pathogenicity of heterozygous variants in this gene.
Ataxia and cerebellar anomalies - narrow panel v2.317 COG5 Arina Puzriakova Mode of inheritance for gene: COG5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v3.1771 FBXW7 Arina Puzriakova Phenotypes for gene: FBXW7 were changed from Neurodevelopmental abnormality; Global developmental delay; Intellectual disability; Macrocephaly; Microcephaly; Abnormality of brain morphology; Abnormality of the corpus callosum; Abnormality of the cerebellum; Abnormality of the cardiovascular system; Seizures; Strabismus; Abnormality of the palate to Developmental delay, hypotonia, and impaired language, OMIM:620012
Intellectual disability v3.1770 TAB2 Arina Puzriakova Phenotypes for gene: TAB2 were changed from Congenital heart defects, nonsyndromic, 2, 614980 to Congenital heart defects, nonsyndromic, 2, OMIM:614980
Paediatric or syndromic cardiomyopathy v1.83 TAB2 Arina Puzriakova Phenotypes for gene: TAB2 were changed from to Congenital heart defects, nonsyndromic, 2, OMIM:614980
Fetal anomalies v1.992 TAB2 Arina Puzriakova Phenotypes for gene: TAB2 were changed from CONGENITAL HEART DISEASE, NONSYNDROMIC, 2 to Congenital heart defects, nonsyndromic, 2, OMIM:614980
Hereditary neuropathy or pain disorder v1.105 ARHGEF10 Dmitrijs Rots reviewed gene: ARHGEF10: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary neuropathy v1.457 ARHGEF10 Dmitrijs Rots reviewed gene: ARHGEF10: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Leber hereditary optic neuropathy v1.13 DNAJC30 Eleanor Williams Classified gene: DNAJC30 as No list
Leber hereditary optic neuropathy v1.13 DNAJC30 Eleanor Williams Added comment: Comment on list classification: Demoting from Green to Grey as this gene has been removed from the R42 (Leber hereditary optic neuropathy) clinical indication in v4 of the National Genomic Test Directory (October 2022).
Leber hereditary optic neuropathy v1.13 DNAJC30 Eleanor Williams Gene: dnajc30 has been removed from the panel.
Retinal disorders v2.301 AIPL1 Arina Puzriakova Tag Q4_22_MOI tag was added to gene: AIPL1.
Retinal disorders v2.301 AIPL1 Arina Puzriakova edited their review of gene: AIPL1: Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Retinal disorders v2.301 AIPL1 Arina Puzriakova Added comment: Comment on phenotypes: Previous phenotypes (overwritten): Achromatopsia, Cone, and Cone-rod Dystrophy; Cone-rod dystrophy (AD); Leber congenital amaurosis 4 (AR); Retinitis pigmentosa, juvenile (AD); Leber Congenital Amaurosis; Leber congenital amaurosis; Leber congenital amaurosis 4, 604393; Retinitis pigmentosa, juvenile, 604393; Cone-rod dystrophy, 604393; Eye Disorders; Retinitis Pigmentosa, Dominant; Retinitis Pigmentosa, Recessive; Retinitis pigmentosa
Retinal disorders v2.301 AIPL1 Arina Puzriakova Phenotypes for gene: AIPL1 were changed from Achromatopsia, Cone, and Cone-rod Dystrophy; Cone-rod dystrophy (AD); Leber congenital amaurosis 4 (AR); Retinitis pigmentosa, juvenile (AD); Leber Congenital Amaurosis; Leber congenital amaurosis; Leber congenital amaurosis 4, 604393; Retinitis pigmentosa, juvenile, 604393; Cone-rod dystrophy, 604393; Eye Disorders; Retinitis Pigmentosa, Dominant; Retinitis Pigmentosa, Recessive; Retinitis pigmentosa to Cone-rod dystrophy, OMIM:604393; Retinitis pigmentosa, juvenile, OMIM:604393; Leber congenital amaurosis 4, OMIM:604393
Retinal disorders v2.300 AIPL1 Arina Puzriakova Publications for gene: AIPL1 were set to
Retinal disorders v2.299 AIPL1 Arina Puzriakova Added comment: Comment on mode of inheritance: MOI should be updated from 'biallelic' to 'both mono- and biallelic (but biallelic mutations cause a more SEVERE disease form) at the next GMS panel update.

This gene is typically associated with recessive inheritance of a Leber congenital amaurosis (LCA) phenotype. However, some patients with heterozygous variants have also been identified, usually presenting less severe phenotypes within the retinal dystrophy spectrum such as retinitis pigmentosa and rod-cone dystrophy/dysfunction - although heterozygous variants act with reduced penetrance (PMID: 10873396; 15249368; 21900377; 33067476)

Both MOIs are also listed in OMIM.
Retinal disorders v2.299 AIPL1 Arina Puzriakova Mode of inheritance for gene: AIPL1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Membranoproliferative glomerulonephritis including C3 glomerulopathy v2.28 CFH Eleanor Williams changed review comment from: Comment on mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; to: Comment on mode of inheritance: Changing the MOI to BIALLELIC, autosomal or pseudoautosomal as per the signed off version 2.13 (Oct 2020) and as agreed with NHSE.
Membranoproliferative glomerulonephritis including C3 glomerulopathy v2.28 CFH Eleanor Williams Added comment: Comment on mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Membranoproliferative glomerulonephritis including C3 glomerulopathy v2.28 CFH Eleanor Williams Mode of inheritance for gene: CFH was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Membranoproliferative glomerulonephritis including C3 glomerulopathy v2.27 DGKE Eleanor Williams Added comment: Comment on mode of inheritance: Changing the MOI to BIALLELIC, autosomal or pseudoautosomal as per the signed off version 2.13 (Oct 2020) and as agreed with NHSE.
Membranoproliferative glomerulonephritis including C3 glomerulopathy v2.27 DGKE Eleanor Williams Mode of inheritance for gene: DGKE was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.316 PITRM1 Eleanor Williams Tag gene-checked tag was added to gene: PITRM1.
Nephrocalcinosis or nephrolithiasis v2.40 WDR72 Detlef Bockenhauer gene: WDR72 was added
gene: WDR72 was added to Nephrocalcinosis or nephrolithiasis. Sources: Expert list
Mode of inheritance for gene: WDR72 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR72 were set to PMID: 30028003; 30779877; 31959358; 33033857
Phenotypes for gene: WDR72 were set to distal renal tubular acidosis; amelogenesis imperfecta
Penetrance for gene: WDR72 were set to Complete
Review for gene: WDR72 was set to GREEN
Added comment: Sources: Expert list
Primary immunodeficiency or monogenic inflammatory bowel disease v2.582 SASH3 Eleanor Williams commented on gene: SASH3
Primary immunodeficiency or monogenic inflammatory bowel disease v2.582 SASH3 Eleanor Williams Tag gene-checked was removed from gene: SASH3.
Severe microcephaly v2.322 PRIM1 Eleanor Williams commented on gene: PRIM1
Severe microcephaly v2.322 PRIM1 Eleanor Williams Phenotypes for gene: PRIM1 were changed from Microcephalic primordial dwarfism, MONDO:0017950 to Microcephalic primordial dwarfism, MONDO:0017950; Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, OMIM:620005
Severe microcephaly v2.321 PRIM1 Eleanor Williams Tag gene-checked was removed from gene: PRIM1.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.582 PRIM1 Eleanor Williams commented on gene: PRIM1
Primary immunodeficiency or monogenic inflammatory bowel disease v2.582 PRIM1 Eleanor Williams Phenotypes for gene: PRIM1 were changed from Microcephalic primordial dwarfism, MONDO:0017950 to Microcephalic primordial dwarfism, MONDO:0017950; Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, OMIM:620005
Primary immunodeficiency or monogenic inflammatory bowel disease v2.581 PRIM1 Eleanor Williams Tag gene-checked was removed from gene: PRIM1.
Fetal anomalies v1.991 PRIM1 Eleanor Williams commented on gene: PRIM1
Fetal anomalies v1.991 PRIM1 Eleanor Williams Phenotypes for gene: PRIM1 were changed from Microcephalic primordial dwarfism, MONDO:0017950 to Microcephalic primordial dwarfism, MONDO:0017950; Primordial dwarfism-immunodeficiency-lipodystrophy syndrome, OMIM:620005
Fetal anomalies v1.990 PRIM1 Eleanor Williams Tag gene-checked was removed from gene: PRIM1.
Intellectual disability v3.1769 JARID2 Eleanor Williams commented on gene: JARID2
Intellectual disability v3.1769 JARID2 Eleanor Williams Phenotypes for gene: JARID2 were changed from Intellectual disability; Neurodevelopmental syndrome to Intellectual disability; Neurodevelopmental syndrome; Developmental delay with variable intellectual disability and dysmorphic facies, OMIM:620098
Intellectual disability v3.1768 JARID2 Eleanor Williams Tag gene-checked was removed from gene: JARID2.
Intellectual disability v3.1768 HNRNPR Eleanor Williams commented on gene: HNRNPR
Intellectual disability v3.1768 HNRNPR Eleanor Williams Phenotypes for gene: HNRNPR were changed from Global developmental delay; Intellectual disability; Seizures; Postnatal microcephaly; Short digit to Global developmental delay; Intellectual disability; Seizures; Postnatal microcephaly; Short digit; Neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities, OMIM:620073
Intellectual disability v3.1767 HNRNPR Eleanor Williams Tag gene-checked was removed from gene: HNRNPR.
Early onset or syndromic epilepsy v2.607 HNRNPR Eleanor Williams commented on gene: HNRNPR
Early onset or syndromic epilepsy v2.607 HNRNPR Eleanor Williams Phenotypes for gene: HNRNPR were changed from Global developmental delay; Intellectual disability; Seizures; Postnatal microcephaly; Short digit to Global developmental delay; Intellectual disability; Seizures; Postnatal microcephaly; Short digit; Neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities, OMIM:620073
Early onset or syndromic epilepsy v2.606 HNRNPR Eleanor Williams Tag gene-checked was removed from gene: HNRNPR.
DDG2P v2.84 HNRNPR Eleanor Williams commented on gene: HNRNPR
DDG2P v2.84 HNRNPR Eleanor Williams Phenotypes for gene: HNRNPR were changed from INTELLECTUAL DISABILITY 616579 to Neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities, OMIM:620073
DDG2P v2.83 HNRNPR Eleanor Williams Tag gene-checked was removed from gene: HNRNPR.
Childhood onset dystonia, chorea or related movement disorder v1.265 HNRNPH1 Eleanor Williams commented on gene: HNRNPH1
Childhood onset dystonia, chorea or related movement disorder v1.265 HNRNPH1 Eleanor Williams Phenotypes for gene: HNRNPH1 were changed from HNRNPH1-related neurodevelopmental disorder to HNRNPH1-related neurodevelopmental disorder; Neurodevelopmental disorder with craniofacial dysmorphism and skeletal defects, OMIM:620083
Childhood onset dystonia, chorea or related movement disorder v1.264 HNRNPH1 Eleanor Williams Tag gene-checked was removed from gene: HNRNPH1.
Intellectual disability v3.1767 HNRNPH1 Eleanor Williams commented on gene: HNRNPH1
Intellectual disability v3.1767 HNRNPH1 Eleanor Williams Phenotypes for gene: HNRNPH1 were changed from HNRNPH1‐related syndromic intellectual disability to HNRNPH1‐related syndromic intellectual disability; Neurodevelopmental disorder with craniofacial dysmorphism and skeletal defects, OMIM:620083
Intellectual disability v3.1766 HNRNPH1 Eleanor Williams Tag gene-checked was removed from gene: HNRNPH1.
Early onset or syndromic epilepsy v2.606 HID1 Eleanor Williams commented on gene: HID1
Early onset or syndromic epilepsy v2.606 HID1 Eleanor Williams Phenotypes for gene: HID1 were changed from Syndromic infantile encephalopathy; Hypopituitarism to Syndromic infantile encephalopathy; Hypopituitarism; Developmental and epileptic encephalopathy 105 with hypopituitarism, OMIM:619983
Early onset or syndromic epilepsy v2.605 HID1 Eleanor Williams Tag gene-checked was removed from gene: HID1.
Pituitary hormone deficiency v2.103 HID1 Eleanor Williams commented on gene: HID1
Pituitary hormone deficiency v2.103 HID1 Eleanor Williams Phenotypes for gene: HID1 were changed from Syndromic infantile encephalopathy; Hypopituitarism to Syndromic infantile encephalopathy; Hypopituitarism; Developmental and epileptic encephalopathy 105 with hypopituitarism, OMIM:619983
Pituitary hormone deficiency v2.102 HID1 Eleanor Williams Tag gene-checked was removed from gene: HID1.
Intellectual disability v3.1766 HID1 Eleanor Williams commented on gene: HID1
Intellectual disability v3.1766 HID1 Eleanor Williams Phenotypes for gene: HID1 were changed from Syndromic infantile encephalopathy; Hypopituitarism to Syndromic infantile encephalopathy; Hypopituitarism; Developmental and epileptic encephalopathy 105 with hypopituitarism, OMIM:619983
Intellectual disability v3.1765 HID1 Eleanor Williams Tag gene-checked was removed from gene: HID1.
Childhood solid tumours cancer susceptibility v1.23 GPR161 Eleanor Williams commented on gene: GPR161
Childhood solid tumours cancer susceptibility v1.23 GPR161 Eleanor Williams Phenotypes for gene: GPR161 were changed from Predisposition to paediatric medulloblastoma to {Medulloblastoma predisposition syndrome}, OMIM:155255
Childhood solid tumours cancer susceptibility v1.22 GPR161 Eleanor Williams Tag gene-checked was removed from gene: GPR161.
Childhood solid tumours v2.38 GPR161 Eleanor Williams commented on gene: GPR161
Childhood solid tumours v2.38 GPR161 Eleanor Williams Phenotypes for gene: GPR161 were changed from Medulloblastoma predisposition to {Medulloblastoma predisposition syndrome}, OMIM:155255
Childhood solid tumours v2.37 GPR161 Eleanor Williams Tag gene-checked was removed from gene: GPR161.
Intellectual disability v3.1765 CACNA1I Eleanor Williams commented on gene: CACNA1I
Early onset or syndromic epilepsy v2.605 CACNA1I Eleanor Williams commented on gene: CACNA1I
Early onset or syndromic epilepsy v2.605 CACNA1I Eleanor Williams Phenotypes for gene: CACNA1I were changed from Neurodevelopmental disorder to Neurodevelopmental disorder with speech impairment and with or without seizures, OMIM:620114
Early onset or syndromic epilepsy v2.604 CACNA1I Eleanor Williams Tag gene-checked was removed from gene: CACNA1I.
Intellectual disability v3.1765 CACNA1I Eleanor Williams Phenotypes for gene: CACNA1I were changed from Neurodevelopmental disorder to Neurodevelopmental disorder with speech impairment and with or without seizures, OMIM:620114
Intellectual disability v3.1764 CACNA1I Eleanor Williams Tag gene-checked was removed from gene: CACNA1I.
Intellectual disability v3.1764 ARFGEF1 Eleanor Williams commented on gene: ARFGEF1
Intellectual disability v3.1764 ARFGEF1 Eleanor Williams Tag gene-checked was removed from gene: ARFGEF1.
Intellectual disability v3.1764 ARFGEF1 Eleanor Williams Phenotypes for gene: ARFGEF1 were changed from Intellectual disability, MONDO:0001071; Epilepsy, MONDO:0005027 to Intellectual disability, MONDO:0001071; Epilepsy, MONDO:0005027; Developmental delay, impaired speech, and behavioral abnormalities, with or without seizures, OMIM:619964
Early onset or syndromic epilepsy v2.604 ARFGEF1 Eleanor Williams commented on gene: ARFGEF1
Early onset or syndromic epilepsy v2.604 ARFGEF1 Eleanor Williams Tag gene-checked was removed from gene: ARFGEF1.
Early onset or syndromic epilepsy v2.604 ARFGEF1 Eleanor Williams Phenotypes for gene: ARFGEF1 were changed from Intellectual disability, MONDO:0001071; Epilepsy, MONDO:0005027 to Intellectual disability, MONDO:0001071; Epilepsy, MONDO:0005027; Developmental delay, impaired speech, and behavioral abnormalities, with or without seizures, OMIM:619964
Structural eye disease v1.152 DDX58 Eleanor Williams commented on gene: DDX58
Structural eye disease v1.152 DDX58 Eleanor Williams Tag new-gene-name tag was added to gene: DDX58.
Intellectual disability v3.1763 DDX58 Eleanor Williams commented on gene: DDX58
Intellectual disability v3.1763 DDX58 Eleanor Williams Tag new-gene-name tag was added to gene: DDX58.
DDG2P v2.83 DDX58 Eleanor Williams commented on gene: DDX58
DDG2P v2.83 DDX58 Eleanor Williams Tag new-gene-name tag was added to gene: DDX58.
COVID-19 research v1.134 DDX58 Eleanor Williams commented on gene: DDX58
COVID-19 research v1.134 DDX58 Eleanor Williams Tag new-gene-name tag was added to gene: DDX58.
Glaucoma (developmental) v1.42 DDX58 Eleanor Williams commented on gene: DDX58
Glaucoma (developmental) v1.42 DDX58 Eleanor Williams Tag new-gene-name tag was added to gene: DDX58.
Hereditary neuropathy or pain disorder v1.105 FAM126A Eleanor Williams commented on gene: FAM126A
Hereditary neuropathy or pain disorder v1.105 FAM126A Eleanor Williams Tag new-gene-name tag was added to gene: FAM126A.
Structural eye disease v1.152 FAM126A Eleanor Williams commented on gene: FAM126A
Structural eye disease v1.152 FAM126A Eleanor Williams Tag new-gene-name tag was added to gene: FAM126A.
Hereditary neuropathy v1.457 FAM126A Eleanor Williams commented on gene: FAM126A
Hereditary neuropathy v1.457 FAM126A Eleanor Williams Tag new-gene-name tag was added to gene: FAM126A.
DDG2P v2.83 FAM126A Eleanor Williams commented on gene: FAM126A
DDG2P v2.83 FAM126A Eleanor Williams Tag new-gene-name tag was added to gene: FAM126A.
Inherited white matter disorders v1.163 FAM126A Eleanor Williams commented on gene: FAM126A
Inherited white matter disorders v1.163 FAM126A Eleanor Williams Tag new-gene-name tag was added to gene: FAM126A.
Bilateral congenital or childhood onset cataracts v2.111 FAM126A Eleanor Williams commented on gene: FAM126A
Bilateral congenital or childhood onset cataracts v2.111 FAM126A Eleanor Williams Tag new-gene-name tag was added to gene: FAM126A.
Fetal anomalies v1.990 FAM126A Eleanor Williams commented on gene: FAM126A
Fetal anomalies v1.990 FAM126A Eleanor Williams Tag new-gene-name tag was added to gene: FAM126A.
Intellectual disability v3.1763 FAM126A Eleanor Williams commented on gene: FAM126A
Intellectual disability v3.1763 FAM126A Eleanor Williams Tag new-gene-name tag was added to gene: FAM126A.
White matter disorders and cerebral calcification - narrow panel v1.246 FAM126A Eleanor Williams commented on gene: FAM126A
White matter disorders and cerebral calcification - narrow panel v1.246 FAM126A Eleanor Williams Tag new-gene-name tag was added to gene: FAM126A.
Familial melanoma v1.14 TERT Arina Puzriakova Publications for gene: TERT were set to 23348503
Familial melanoma v1.13 TERT Arina Puzriakova Tag watchlist tag was added to gene: TERT.
Familial melanoma v1.13 TERT Arina Puzriakova reviewed gene: TERT: Rating: ; Mode of pathogenicity: None; Publications: 23348503, 23348506, 35912549; Phenotypes: {Melanoma, cutaneous malignant, 9}, OMIM:615134; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary ataxia with onset in adulthood v2.169 TERT Arina Puzriakova Publications for gene: TERT were set to
Hereditary ataxia with onset in adulthood v2.168 TERT Arina Puzriakova Classified gene: TERT as Green List (high evidence)
Hereditary ataxia with onset in adulthood v2.168 TERT Arina Puzriakova Added comment: Comment on list classification: This gene should be demoted from Green to Red at the next GMS panel update as there is no link with adult-onset ataxia associated with this gene.

Cerebellar hypoplasia (but without ataxia) has been identified in 2/5 unrelated AR cases to date, who displayed a phenotype of Hoyeraal-Hreidarsson syndrome, a severe variant of DKC (PMIDs: 17785587; 34890115). Furthermore, literature search only revealed a single adult patient (31 years old) who did not present any signs of ataxia (PMID: 18042801).
Hereditary ataxia with onset in adulthood v2.168 TERT Arina Puzriakova Gene: tert has been classified as Green List (High Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.316 TERT Arina Puzriakova changed review comment from: Cerebellar hypoplasia (without ataxia) has been identified in 2/5 unrelated AR cases who displayed a phenotype of Hoyeraal-Hreidarsson syndrome, a severe variant of DKC (PMIDs: 17785587; 34890115).

There is no link with AD form and given the various other non-relevant phenotypes linked to heterozygous variants, AR inheritance is appropriate for this panel.; to: Cerebellar hypoplasia (without ataxia) has been identified in 2/5 unrelated AR cases to date, who displayed a phenotype of Hoyeraal-Hreidarsson syndrome, a severe variant of DKC (PMIDs: 17785587; 34890115).

There is no link with AD form and given the various other non-relevant phenotypes linked to heterozygous variants, AR inheritance is appropriate for this panel.
Hereditary ataxia with onset in adulthood v2.167 TERT Arina Puzriakova Tag Q4_22_demote_red tag was added to gene: TERT.
Cerebellar hypoplasia v1.70 TERT Arina Puzriakova Publications for gene: TERT were set to 17785587; 16247010
Cerebellar hypoplasia v1.69 TERT Arina Puzriakova reviewed gene: TERT: Rating: AMBER; Mode of pathogenicity: None; Publications: 17785587, 34890115; Phenotypes: Dyskeratosis congenita, autosomal recessive 4, OMIM:613989; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.316 TERT Arina Puzriakova changed review comment from: Cerebellar hypoplasia (without ataxia) has been identified in 2/5 unrelated AR cases displaying a phenotype of Hoyeraal-Hreidarsson syndrome, a severe variant of DKC (PMIDs: 17785587; 34890115).

There is no link with AD form and given the various other non-relevant phenotypes linked to heterozygous variants, AR inheritance is appropriate for this panel.; to: Cerebellar hypoplasia (without ataxia) has been identified in 2/5 unrelated AR cases who displayed a phenotype of Hoyeraal-Hreidarsson syndrome, a severe variant of DKC (PMIDs: 17785587; 34890115).

There is no link with AD form and given the various other non-relevant phenotypes linked to heterozygous variants, AR inheritance is appropriate for this panel.
Ataxia and cerebellar anomalies - narrow panel v2.316 TERT Arina Puzriakova Tag watchlist tag was added to gene: TERT.
Ataxia and cerebellar anomalies - narrow panel v2.316 TERT Arina Puzriakova Classified gene: TERT as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v2.316 TERT Arina Puzriakova Gene: tert has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.315 TERT Arina Puzriakova reviewed gene: TERT: Rating: AMBER; Mode of pathogenicity: None; Publications: 17785587, 34890115; Phenotypes: Dyskeratosis congenita, autosomal recessive 4, OMIM:613989; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary ataxia with onset in adulthood v2.167 TERT Arina Puzriakova Phenotypes for gene: TERT were changed from Dyskeratosis congenita, 613989 to Dyskeratosis congenita, autosomal recessive 4, OMIM:613989
Ataxia and cerebellar anomalies - narrow panel v2.315 TERT Arina Puzriakova Deleted their review
Ataxia and cerebellar anomalies - narrow panel v2.315 TERT Arina Puzriakova Deleted their comment
Ataxia and cerebellar anomalies - narrow panel v2.315 TERT Arina Puzriakova Phenotypes for gene: TERT were changed from Dyskeratosis congenita, autosomal dominant 2, OMIM:613989; Dyskeratosis congenita, autosomal recessive 4, OMIM:613989 to Dyskeratosis congenita, autosomal recessive 4, OMIM:613989
Ataxia and cerebellar anomalies - narrow panel v2.314 TERT Arina Puzriakova Mode of inheritance for gene: TERT was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Cerebellar hypoplasia v1.69 TERT Arina Puzriakova Phenotypes for gene: TERT were changed from Dyskeratosis congenita, autosomal dominant 2, OMIM:613989; Dyskeratosis congenita, autosomal recessive 4, OMIM:613989 to Dyskeratosis congenita, autosomal recessive 4, OMIM:613989
Intellectual disability v3.1763 TERT Arina Puzriakova Phenotypes for gene: TERT were changed from Dyskeratosis congenita, autosomal recessive 4 to Dyskeratosis congenita, autosomal recessive 4, OMIM:613989
Adult solid tumours cancer susceptibility v2.24 TERT Arina Puzriakova Phenotypes for gene: TERT were changed from {Dyskeratosis congenita, autosomal recessive 4}, 613989; {Dyskeratosis congenita, autosomal dominant 2}, 613989 to Dyskeratosis congenita, autosomal dominant 2, OMIM:613989; Dyskeratosis congenita, autosomal recessive 4, OMIM:613989; Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1, OMIM:614742; {Leukemia, acute myeloid}, OMIM:601626; {Melanoma, cutaneous malignant, 9}, OMIM:615134
Cerebellar hypoplasia v1.68 TERT Arina Puzriakova Phenotypes for gene: TERT were changed from dyskeratosis congenita-2 to Dyskeratosis congenita, autosomal dominant 2, OMIM:613989; Dyskeratosis congenita, autosomal recessive 4, OMIM:613989
Skeletal dysplasia v2.228 TERT Arina Puzriakova Phenotypes for gene: TERT were changed from Dyskeratosis congenita, autosomal dominant 2 and autosomal recessive 4 613989 to Dyskeratosis congenita, autosomal dominant 2, OMIM:613989; Dyskeratosis congenita, autosomal recessive 4, OMIM:613989
Childhood solid tumours cancer susceptibility v1.22 TERT Arina Puzriakova Phenotypes for gene: TERT were changed from Dynkeratosis Congenita to Dyskeratosis congenita, autosomal dominant 2, OMIM:613989; Dyskeratosis congenita, autosomal recessive 4, OMIM:613989; Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1, OMIM:614742; {Leukemia, acute myeloid}, OMIM:601626; {Melanoma, cutaneous malignant, 9}, OMIM:615134
Primary immunodeficiency or monogenic inflammatory bowel disease v2.581 TERT Arina Puzriakova Phenotypes for gene: TERT were changed from Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation; microcephaly, neurodevelopmental delay; Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation; microcephaly, neurodevelopmental delay; Bone marrow failure to Dyskeratosis congenita, autosomal dominant 2, OMIM:613989; Dyskeratosis congenita, autosomal recessive 4, OMIM:613989
Pigmentary skin disorders v1.54 TERT Arina Puzriakova Phenotypes for gene: TERT were changed from DYSKERATOSIS CONGENITA, AUTOSOMAL DOMINANT 2; DKCA2, DYSKERATOSIS CONGENITA, AUTOSOMAL RECESSIVE 4, INCLUDED; Melanoma; Dyskeratosis congenita; DKCB4, INCLUDED to Dyskeratosis congenita, autosomal dominant 2, OMIM:613989; Dyskeratosis congenita, autosomal recessive 4, OMIM:613989
Familial melanoma v1.13 TERT Arina Puzriakova Phenotypes for gene: TERT were changed from to {Melanoma, cutaneous malignant, 9}, OMIM:615134
COVID-19 research v1.134 TERT Arina Puzriakova Phenotypes for gene: TERT were changed from Bone marrow failure; Bone marrow failure, pulmonary and hepatic fibrosis, nail dystrophy, leukoplakia, reticulate skin pigmentation; microcephaly, neurodevelopmental delay to Dyskeratosis congenita, autosomal dominant 2, OMIM:613989; Dyskeratosis congenita, autosomal recessive 4, OMIM:613989
Childhood solid tumours v2.37 TERT Arina Puzriakova Phenotypes for gene: TERT were changed from {Dyskeratosis congenita, autosomal recessive 4}, 613989; {Dyskeratosis congenita, autosomal dominant 2}, 613989 to Dyskeratosis congenita, autosomal dominant 2, OMIM:613989; Dyskeratosis congenita, autosomal recessive 4, OMIM:613989; Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1, OMIM:614742; {Leukemia, acute myeloid}, OMIM:601626; {Melanoma, cutaneous malignant, 9}, OMIM:615134
Ataxia and cerebellar anomalies - narrow panel v2.313 TERT Arina Puzriakova Classified gene: TERT as Red List (low evidence)
Ataxia and cerebellar anomalies - narrow panel v2.313 TERT Arina Puzriakova Added comment: Comment on list classification: Couldn't find any evidence linking TERT with ataxia and therefore demoting from Amber to Red.
Ataxia and cerebellar anomalies - narrow panel v2.313 TERT Arina Puzriakova Gene: tert has been classified as Red List (Low Evidence).
Ataxia and cerebellar anomalies - narrow panel v2.312 TERT Arina Puzriakova Mode of inheritance for gene: TERT was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v2.311 TERT Arina Puzriakova Phenotypes for gene: TERT were changed from dyskeratosis congenita-2 to Dyskeratosis congenita, autosomal dominant 2, OMIM:613989; Dyskeratosis congenita, autosomal recessive 4, OMIM:613989
Familial pulmonary fibrosis v1.30 TERT Arina Puzriakova Phenotypes for gene: TERT were changed from {Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1}, 614742; Familial Pulmonary Fibrosis; Pulmonary Fibrosis and Hermansky-Pudlak Syndrome; Pulmonary Disease to Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1, OMIM:614742
Cytopenia - NOT Fanconi anaemia v1.73 TERT Arina Puzriakova Phenotypes for gene: TERT were changed from {Pulmonary fibrosis, telomere-related, 1}, 614742; {Dyskeratosis congenita, autosomal dominant 2}, 613989; Coronary artery disease; {Melanoma, cutaneous malignant, 9}, 615134; 614742 Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1; Aplastic Anemia; 614742 {Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1}; {Leukemia, acute myeloid}, 601626; 613989 Dyskeratosis congenita; {Dyskeratosis congenita, autosomal recessive 4}, 613989 to Dyskeratosis congenita, autosomal dominant 2, OMIM:613989; Dyskeratosis congenita, autosomal recessive 4, OMIM:613989; Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1, OMIM:614742
Inherited predisposition to acute myeloid leukaemia (AML) v1.25 TERT Arina Puzriakova Phenotypes for gene: TERT were changed from {Leukemia, acute myeloid}, OMIM:601626; Dyskeratosis congenita, autosomal dominant 2, OMIM:613989; Dyskeratosis congenita, autosomal recessive 4, OMIM:613989 to {Leukemia, acute myeloid}, OMIM:601626; Dyskeratosis congenita, autosomal dominant 2, OMIM:613989; Dyskeratosis congenita, autosomal recessive 4, OMIM:613989; Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1, OMIM:614742
Haematological malignancies for rare disease v1.16 TERT Arina Puzriakova Phenotypes for gene: TERT were changed from {Leukemia, acute myeloid}, OMIM:601626; Dyskeratosis congenita, autosomal dominant 2, OMIM:613989; Dyskeratosis congenita, autosomal recessive 4, OMIM:613989 to {Leukemia, acute myeloid}, OMIM:601626; Dyskeratosis congenita, autosomal dominant 2, OMIM:613989; Dyskeratosis congenita, autosomal recessive 4, OMIM:613989; Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1, OMIM:614742
Haematological malignancies cancer susceptibility v2.39 TERT Arina Puzriakova Phenotypes for gene: TERT were changed from Class: BM failure syndrome (typ AR); Dyskeratosis congenita; MDS, AML; Bone marrow failure, macrocytosis; Skin, head and neck, and anogenital squamous cell cancers, Oral and GI squamous cell carcinoma to {Leukemia, acute myeloid}, OMIM:601626; Dyskeratosis congenita, autosomal dominant 2, OMIM:613989; Dyskeratosis congenita, autosomal recessive 4, OMIM:613989; Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1, OMIM:614742
Cytopenias and congenital anaemias v1.111 TERT Arina Puzriakova Phenotypes for gene: TERT were changed from Aplastic Anemia; Coronary artery disease; {Dyskeratosis congenita, autosomal recessive 4}, 613989; {Dyskeratosis congenita, autosomal dominant 2}, 613989; {Pulmonary fibrosis, telomere-related, 1}, 614742; {Leukemia, acute myeloid}, 601626; {Melanoma, cutaneous malignant, 9}, 615134 to Dyskeratosis congenita, autosomal dominant 2, OMIM:613989; Dyskeratosis congenita, autosomal recessive 4, OMIM:613989; Pulmonary fibrosis and/or bone marrow failure, telomere-related, 1, OMIM:614742 (AD)
Haematological malignancies for rare disease v1.15 TERT Arina Puzriakova Phenotypes for gene: TERT were changed from Class: BM failure syndrome (typ AR); Dyskeratosis congenita; MDS, AML; Bone marrow failure, macrocytosis; Skin, head and neck, and anogenital squamous cell cancers, Oral and GI squamous cell carcinoma to {Leukemia, acute myeloid}, OMIM:601626; Dyskeratosis congenita, autosomal dominant 2, OMIM:613989; Dyskeratosis congenita, autosomal recessive 4, OMIM:613989
Haematological malignancies cancer susceptibility v2.38 MBD4 Arina Puzriakova changed review comment from: Re-tagging on this panel following a separate Green expert review on a different GMS panel (R347, R211) to ensure that if the decision is made to include the gene, all panels are appropriately updated.; to: Re-tagging on this panel following a new Green expert review by Dr Claire Palles on a different GMS panel (R347, R211) to ensure that if the decision is made to include the gene, all panels are appropriately updated.

Loss of MBD4 leads to an accumulation of somatic CpG>TpG transitions, consistent with MBD4 function which involves repair of G:T mismatches resulting from deamination of 5'-methylcytosine. Germline MBD4 inactivation can therefore lead to somatic variation (i.e. CpG>TpG) in well-known cancer driver genes, in turn conferring cancer susceptibility. Although MBD4 itself does not directly drive oncogenesis, evidence suggests it may modify disease risk as shown by multiple cases reported in literature with this distinctive mutational signature.
Haematological malignancies cancer susceptibility v2.38 RAD21 Arina Puzriakova Tag missense tag was added to gene: RAD21.
Haematological malignancies cancer susceptibility v2.38 RAD21 Arina Puzriakova Mode of pathogenicity for gene: RAD21 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to None
Haematological malignancies cancer susceptibility v2.37 RAD21 Arina Puzriakova Tag Q4_22_promote_green tag was added to gene: RAD21.
Tag Q4_22_expert_review tag was added to gene: RAD21.
Haematological malignancies cancer susceptibility v2.37 RAD21 Arina Puzriakova Classified gene: RAD21 as Amber List (moderate evidence)
Haematological malignancies cancer susceptibility v2.37 RAD21 Arina Puzriakova Added comment: Comment on list classification: RAD21 will be flagged for expert review at the next GMS panel update to determine whether there is enough evidence to classify this gene as Green.

Somatic variants have been found in multiple AML cohorts (PMID: 34157074); however, only one recurrent germline variant (c.892C>T/G, p.P298S/A) was found in three unrelated children with lymphoblastic leukemia or lymphoma (PMID:35563565). The same variant was also found in an adult patient with a solid tumour (malignant peripheral nerve sheath tumour).
Functional studies showed the variant disrupted RAD21 gene expression and DNA damage response but did not perturb formation of the cohesin complex. Notably 2/3 patients harboured known pathogenic somatic KRAS hot-spot variants.

Heterozygous variants in the RAD21 gene are also associated with Cornelia-de-Lange syndrome (MIM# 614701) which is not known to confer cancer predisposition.
Haematological malignancies cancer susceptibility v2.37 RAD21 Arina Puzriakova Gene: rad21 has been classified as Amber List (Moderate Evidence).
Catecholaminergic polymorphic VT v2.21 CALM2 Sarah Leigh Phenotypes for gene: CALM2 were changed from catecholaminergic polymorphic ventricular tachycardia, MONDO:0017990 to Long QT syndrome 15, OMIM:616249; long QT syndrome 15, MONDO:0014550
Long QT syndrome v2.34 CALM2 Sarah Leigh Phenotypes for gene: CALM2 were changed from Long QT syndrome 15 to Long QT syndrome 15, OMIM:616249; long QT syndrome 15, MONDO:0014550
Catecholaminergic polymorphic VT v2.20 CALM2 Sarah Leigh Publications for gene: CALM2 were set to 27114410; 27100291; 24917665
Long QT syndrome v2.33 CALM2 Sarah Leigh Publications for gene: CALM2 were set to
Clefting v2.73 RAD21 Arina Puzriakova Classified gene: RAD21 as Amber List (moderate evidence)
Clefting v2.73 RAD21 Arina Puzriakova Gene: rad21 has been classified as Amber List (Moderate Evidence).
Clefting v2.72 RAD21 Arina Puzriakova gene: RAD21 was added
gene: RAD21 was added to Clefting. Sources: Literature
Q4_22_promote_green tags were added to gene: RAD21.
Mode of inheritance for gene: RAD21 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RAD21 were set to 22633399; 27882533; 31334757; 32193685
Phenotypes for gene: RAD21 were set to Cornelia de Lange syndrome 4, OMIM:614701
Review for gene: RAD21 was set to GREEN
Added comment: At least 33 unrelated families published with RAD21 alterations. Of these, 6 cases presented with cleft palate or submucous cleft palate. Although only displayed by a subset of patients, clefting is a congenital anomaly that may aid earlier diagnosis if other features such as ID have not yet become apparent. Therefore there would be value in including RAD21 on this panel with a Green rating.
Sources: Literature
Intellectual disability v3.1762 RAD21 Arina Puzriakova Publications for gene: RAD21 were set to
Skeletal dysplasia v2.227 RAD21 Arina Puzriakova Publications for gene: RAD21 were set to 22633399; 30716475; 24378232; 27882533; 27620904
Intellectual disability v3.1761 RAD21 Arina Puzriakova Phenotypes for gene: RAD21 were changed from Cornelia de Lange syndrome 4, 614701; COHESINOPATHY to Cornelia de Lange syndrome 4, OMIM:614701
Radial dysplasia v1.22 RAD21 Arina Puzriakova Classified gene: RAD21 as Amber List (moderate evidence)
Radial dysplasia v1.22 RAD21 Arina Puzriakova Added comment: Comment on list classification: Although limb abnormalities are a common feature of CdLS, only minor skeletal anomalies are associated with RAD21 variants. Other prominent features such as ID are more likely to prompt testing and therefore maintaining the Amber rating on skeletal panels for now.

Krab et al. 2020 (PMID: 32193685) collated details on 33 unrelated families (previously and newly published) with RAD21 alterations. In the 22 families with sufficient clinical data available, authors noted that major limb malformations are generally not present. However, minor skeletal anomalies such as clinodactyly of fifth finger (13), camptodactyly (3), scoliosis (2), hip dislocation/dysplasia (2) are reported.
Radial dysplasia v1.22 RAD21 Arina Puzriakova Gene: rad21 has been classified as Amber List (Moderate Evidence).
Radial dysplasia v1.21 RAD21 Arina Puzriakova Publications for gene: RAD21 were set to 22633399; 31334757; 32193685
Skeletal dysplasia v2.226 RAD21 Arina Puzriakova Classified gene: RAD21 as Amber List (moderate evidence)
Skeletal dysplasia v2.226 RAD21 Arina Puzriakova Added comment: Comment on list classification: Although limb abnormalities are a common feature of CdLS, only minor skeletal anomalies are associated with RAD21 variants. Other prominent features such as ID are more likely to prompt testing and therefore maintaining the Amber rating on skeletal panels for now.
Skeletal dysplasia v2.226 RAD21 Arina Puzriakova Gene: rad21 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v2.225 RAD21 Arina Puzriakova reviewed gene: RAD21: Rating: ; Mode of pathogenicity: None; Publications: 32193685; Phenotypes: Cornelia de Lange syndrome 4, OMIM:614701; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Radial dysplasia v1.20 RAD21 Arina Puzriakova Tag watchlist was removed from gene: RAD21.
Radial dysplasia v1.20 RAD21 Arina Puzriakova Publications for gene: RAD21 were set to 22633399; 31334757
Skeletal dysplasia v2.225 RAD21 Arina Puzriakova Phenotypes for gene: RAD21 were changed from Cornelia de Lange syndrome 4 614701 to Cornelia de Lange syndrome 4, OMIM:614701
Radial dysplasia v1.19 RAD21 Arina Puzriakova Phenotypes for gene: RAD21 were changed from Cornelia de Lange syndrome 4, 614701 to Cornelia de Lange syndrome 4, OMIM:614701
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
Deafness and congenital structural abnormalities v1.22 FOXI3 Arina Puzriakova Classified gene: FOXI3 as Green List (high evidence)
Deafness and congenital structural abnormalities v1.22 FOXI3 Arina Puzriakova Added comment: Comment on list classification: Promoting from Red to Green as 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.
Deafness and congenital structural abnormalities v1.22 FOXI3 Arina Puzriakova Gene: foxi3 has been classified as Green List (High Evidence).
Deafness and congenital structural abnormalities v1.21 FOXI3 Arina Puzriakova Publications for gene: FOXI3 were set to
Deafness and congenital structural abnormalities v1.20 FOXI3 Arina Puzriakova Mode of inheritance for gene: FOXI3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Deafness and congenital structural abnormalities v1.19 FOXI3 Arina Puzriakova reviewed gene: FOXI3: Rating: GREEN; Mode of pathogenicity: None; Publications: 36260083, 25655429, 18787161, 24650709; Phenotypes: Microtia with or without atresia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v1.990 KDM5C Arina Puzriakova Phenotypes for gene: KDM5C were changed from MENTAL RETARDATION SYNDROMIC X-LINKED JARID1C-RELATED to Mental retardation, X-linked, syndromic, Claes-Jensen type, OMIM:300534
Fetal anomalies v1.989 KDM5C Arina Puzriakova Publications for gene: KDM5C were set to
Fetal anomalies v1.988 KDM5C Arina Puzriakova Added comment: Comment on mode of inheritance: A subset of female carriers have been shown to have impaired intellectual development and/or developmental delay (PMIDs: 10982473; 16538222; 18697827; 19826449; 21575681; 32279304) showing that females can be symptomatic.

Therefore, the MOI should be updated from 'X-linked.. biallelic in females' to 'X-linked.. monoallelic in females may cause disease' at the next GMS panel update. This also reflects the current MOI on all other relevant panels.