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Fetal anomalies v5.16 UNC45A Achchuthan Shanmugasundram commented on gene: UNC45A
Fetal anomalies v5.16 UFSP2 Achchuthan Shanmugasundram commented on gene: UFSP2
Fetal anomalies v5.16 U2AF2 Achchuthan Shanmugasundram commented on gene: U2AF2
Fetal anomalies v5.16 TYROBP Achchuthan Shanmugasundram commented on gene: TYROBP
Fetal anomalies v5.16 TULP3 Achchuthan Shanmugasundram commented on gene: TULP3
Fetal anomalies v5.16 TUFM Achchuthan Shanmugasundram commented on gene: TUFM
Fetal anomalies v5.16 TTC25 Achchuthan Shanmugasundram commented on gene: TTC25
Fetal anomalies v5.16 TSHZ3 Achchuthan Shanmugasundram commented on gene: TSHZ3
Fetal anomalies v5.16 TRPM7 Achchuthan Shanmugasundram commented on gene: TRPM7
Fetal anomalies v5.16 TRIT1 Achchuthan Shanmugasundram commented on gene: TRIT1
Fetal anomalies v5.16 TREM2 Achchuthan Shanmugasundram commented on gene: TREM2
Fetal anomalies v5.16 TONSL Achchuthan Shanmugasundram commented on gene: TONSL
Fetal anomalies v5.16 TOMM7 Achchuthan Shanmugasundram commented on gene: TOMM7
Fetal anomalies v5.16 TOGARAM1 Achchuthan Shanmugasundram commented on gene: TOGARAM1
Fetal anomalies v5.16 TNRC6B Achchuthan Shanmugasundram commented on gene: TNRC6B
Fetal anomalies v5.16 TNFSF11 Achchuthan Shanmugasundram commented on gene: TNFSF11
Fetal anomalies v5.16 TNFRSF13B Achchuthan Shanmugasundram commented on gene: TNFRSF13B
Fetal anomalies v5.16 THSD1 Achchuthan Shanmugasundram commented on gene: THSD1
Fetal anomalies v5.16 TBR1 Achchuthan Shanmugasundram commented on gene: TBR1
Fetal anomalies v5.16 TAF8 Achchuthan Shanmugasundram commented on gene: TAF8
Fetal anomalies v5.16 TACR3 Achchuthan Shanmugasundram commented on gene: TACR3
Fetal anomalies v5.16 TAC3 Achchuthan Shanmugasundram commented on gene: TAC3
Fetal anomalies v5.16 STX5 Achchuthan Shanmugasundram commented on gene: STX5
Fetal anomalies v5.16 STAG1 Achchuthan Shanmugasundram commented on gene: STAG1
Fetal anomalies v5.16 SPIN4 Achchuthan Shanmugasundram commented on gene: SPIN4
Fetal anomalies v5.16 SNUPN Achchuthan Shanmugasundram commented on gene: SNUPN
Fetal anomalies v5.16 SNRPE Achchuthan Shanmugasundram commented on gene: SNRPE
Fetal anomalies v5.16 SNF8 Achchuthan Shanmugasundram commented on gene: SNF8
Fetal anomalies v5.16 SNAP25 Achchuthan Shanmugasundram commented on gene: SNAP25
Fetal anomalies v5.16 SMPD1 Achchuthan Shanmugasundram commented on gene: SMPD1
Fetal anomalies v5.16 SMOC2 Achchuthan Shanmugasundram commented on gene: SMOC2
Fetal anomalies v5.16 SLCO2A1 Achchuthan Shanmugasundram commented on gene: SLCO2A1
Fetal anomalies v5.16 SLC4A10 Achchuthan Shanmugasundram commented on gene: SLC4A10
Fetal anomalies v5.16 SLC35A1 Achchuthan Shanmugasundram commented on gene: SLC35A1
Fetal anomalies v5.16 SLC34A3 Achchuthan Shanmugasundram commented on gene: SLC34A3
Fetal anomalies v5.16 SLC34A1 Achchuthan Shanmugasundram commented on gene: SLC34A1
Fetal anomalies v5.16 SLC30A7 Achchuthan Shanmugasundram commented on gene: SLC30A7
Fetal anomalies v5.16 SLC25A4 Achchuthan Shanmugasundram commented on gene: SLC25A4
Fetal anomalies v5.16 SLC24A4 Achchuthan Shanmugasundram commented on gene: SLC24A4
Fetal anomalies v5.16 SIAH1 Achchuthan Shanmugasundram commented on gene: SIAH1
Fetal anomalies v5.16 SHROOM4 Achchuthan Shanmugasundram commented on gene: SHROOM4
Fetal anomalies v5.16 SHROOM3 Achchuthan Shanmugasundram commented on gene: SHROOM3
Fetal anomalies v5.16 SH3BP2 Achchuthan Shanmugasundram commented on gene: SH3BP2
Fetal anomalies v5.16 SGMS2 Achchuthan Shanmugasundram commented on gene: SGMS2
Fetal anomalies v5.16 SFRP4 Achchuthan Shanmugasundram commented on gene: SFRP4
Fetal anomalies v5.16 SETD1A Achchuthan Shanmugasundram commented on gene: SETD1A
Fetal anomalies v5.16 SCYL2 Achchuthan Shanmugasundram commented on gene: SCYL2
Fetal anomalies v5.16 SASS6 Achchuthan Shanmugasundram commented on gene: SASS6
Fetal anomalies v5.16 RSPRY1 Achchuthan Shanmugasundram commented on gene: RSPRY1
Fetal anomalies v5.16 RSPO2 Achchuthan Shanmugasundram commented on gene: RSPO2
Fetal anomalies v5.16 RRAS Achchuthan Shanmugasundram commented on gene: RRAS
Fetal anomalies v5.16 RRAGC Achchuthan Shanmugasundram commented on gene: RRAGC
Fetal anomalies v5.16 RPL13 Achchuthan Shanmugasundram commented on gene: RPL13
Fetal anomalies v5.16 ROBO2 Achchuthan Shanmugasundram commented on gene: ROBO2
Fetal anomalies v5.16 ROBO1 Achchuthan Shanmugasundram commented on gene: ROBO1
Fetal anomalies v5.16 RNU4-2 Achchuthan Shanmugasundram commented on gene: RNU4-2
Fetal anomalies v5.16 RINT1 Achchuthan Shanmugasundram commented on gene: RINT1
Fetal anomalies v5.16 RFWD3 Achchuthan Shanmugasundram commented on gene: RFWD3
Fetal anomalies v5.16 RASGRP2 Achchuthan Shanmugasundram commented on gene: RASGRP2
Fetal anomalies v5.16 RAP1B Achchuthan Shanmugasundram commented on gene: RAP1B: This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Fetal anomalies v5.16 RAB34 Achchuthan Shanmugasundram commented on gene: RAB34
Fetal anomalies v5.16 PUM1 Achchuthan Shanmugasundram commented on gene: PUM1
Fetal anomalies v5.16 PSMF1 Achchuthan Shanmugasundram commented on gene: PSMF1
Fetal anomalies v5.16 PSMC3 Achchuthan Shanmugasundram commented on gene: PSMC3
Fetal anomalies v5.16 PSMB9 Achchuthan Shanmugasundram commented on gene: PSMB9
Fetal anomalies v5.16 PRKG2 Achchuthan Shanmugasundram commented on gene: PRKG2
Fetal anomalies v5.16 PRKCSH Achchuthan Shanmugasundram commented on gene: PRKCSH
Fetal anomalies v5.16 PLS3 Achchuthan Shanmugasundram commented on gene: PLS3
Fetal anomalies v5.16 PLD1 Achchuthan Shanmugasundram commented on gene: PLD1
Fetal anomalies v5.16 PKDCC Achchuthan Shanmugasundram commented on gene: PKDCC
Fetal anomalies v5.16 PISD Achchuthan Shanmugasundram commented on gene: PISD
Fetal anomalies v5.16 PIP5K1C Achchuthan Shanmugasundram commented on gene: PIP5K1C
Fetal anomalies v5.16 PIGY Achchuthan Shanmugasundram commented on gene: PIGY
Fetal anomalies v5.16 PIGS Achchuthan Shanmugasundram commented on gene: PIGS
Fetal anomalies v5.16 PIGG Achchuthan Shanmugasundram commented on gene: PIGG
Fetal anomalies v5.16 PI4K2A Achchuthan Shanmugasundram commented on gene: PI4K2A
Fetal anomalies v5.16 PHLDB1 Achchuthan Shanmugasundram commented on gene: PHLDB1
Fetal anomalies v5.16 PAN2 Achchuthan Shanmugasundram commented on gene: PAN2
Fetal anomalies v5.16 NUP214 Achchuthan Shanmugasundram commented on gene: NUP214
Fetal anomalies v5.16 NUDT2 Achchuthan Shanmugasundram commented on gene: NUDT2
Fetal anomalies v5.16 NUAK2 Achchuthan Shanmugasundram commented on gene: NUAK2
Fetal anomalies v5.16 NSUN6 Achchuthan Shanmugasundram commented on gene: NSUN6
Fetal anomalies v5.16 NSUN2 Achchuthan Shanmugasundram commented on gene: NSUN2
Fetal anomalies v5.16 NPR3 Achchuthan Shanmugasundram commented on gene: NPR3
Fetal anomalies v5.16 NPNT Achchuthan Shanmugasundram commented on gene: NPNT
Fetal anomalies v5.16 NLRP3 Achchuthan Shanmugasundram commented on gene: NLRP3: This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Fetal anomalies v5.16 NHP2 Achchuthan Shanmugasundram commented on gene: NHP2
Fetal anomalies v5.16 NARS Achchuthan Shanmugasundram commented on gene: NARS
Fetal anomalies v5.16 MSTO1 Achchuthan Shanmugasundram commented on gene: MSTO1
Fetal anomalies v5.16 MMP2 Achchuthan Shanmugasundram commented on gene: MMP2
Fetal anomalies v5.16 MMP15 Achchuthan Shanmugasundram commented on gene: MMP15
Fetal anomalies v5.16 MIR17HG Achchuthan Shanmugasundram commented on gene: MIR17HG
Fetal anomalies v5.16 MDFIC Achchuthan Shanmugasundram commented on gene: MDFIC: This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Fetal anomalies v5.16 MBOAT7 Achchuthan Shanmugasundram commented on gene: MBOAT7
Fetal anomalies v5.16 MAX Achchuthan Shanmugasundram commented on gene: MAX
Fetal anomalies v5.16 MAPKBP1 Achchuthan Shanmugasundram commented on gene: MAPKBP1
Fetal anomalies v5.16 MAP4K4 Achchuthan Shanmugasundram commented on gene: MAP4K4
Fetal anomalies v5.16 LSM11 Achchuthan Shanmugasundram commented on gene: LSM11
Fetal anomalies v5.16 LRRK1 Achchuthan Shanmugasundram commented on gene: LRRK1
Fetal anomalies v5.16 LRIG2 Achchuthan Shanmugasundram commented on gene: LRIG2
Fetal anomalies v5.16 LRBA Achchuthan Shanmugasundram commented on gene: LRBA
Fetal anomalies v5.16 LRAT Achchuthan Shanmugasundram commented on gene: LRAT
Fetal anomalies v5.16 LPIN2 Achchuthan Shanmugasundram commented on gene: LPIN2
Fetal anomalies v5.16 LOX Achchuthan Shanmugasundram commented on gene: LOX
Fetal anomalies v5.16 LNPK Achchuthan Shanmugasundram commented on gene: LNPK
Fetal anomalies v5.16 LIPT2 Achchuthan Shanmugasundram commented on gene: LIPT2
Fetal anomalies v5.16 LIPN Achchuthan Shanmugasundram commented on gene: LIPN
Fetal anomalies v5.16 LINS1 Achchuthan Shanmugasundram commented on gene: LINS1
Fetal anomalies v5.16 LAMB2 Achchuthan Shanmugasundram commented on gene: LAMB2
Fetal anomalies v5.16 LAMA5 Achchuthan Shanmugasundram commented on gene: LAMA5
Fetal anomalies v5.16 KPTN Achchuthan Shanmugasundram commented on gene: KPTN
Fetal anomalies v5.16 KMT2B Achchuthan Shanmugasundram commented on gene: KMT2B
Fetal anomalies v5.16 KIF5B Achchuthan Shanmugasundram commented on gene: KIF5B
Fetal anomalies v5.16 KIF26A Achchuthan Shanmugasundram commented on gene: KIF26A
Fetal anomalies v5.16 KIF24 Achchuthan Shanmugasundram commented on gene: KIF24
Fetal anomalies v5.16 KDR Achchuthan Shanmugasundram commented on gene: KDR
Fetal anomalies v5.16 KDM5A Achchuthan Shanmugasundram commented on gene: KDM5A
Fetal anomalies v5.16 KDM2B Achchuthan Shanmugasundram commented on gene: KDM2B
Fetal anomalies v5.16 KDELR2 Achchuthan Shanmugasundram commented on gene: KDELR2
Fetal anomalies v5.16 KCNT1 Achchuthan Shanmugasundram commented on gene: KCNT1: This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Fetal anomalies v5.16 KCNN3 Achchuthan Shanmugasundram commented on gene: KCNN3
Fetal anomalies v5.16 KCNK9 Achchuthan Shanmugasundram commented on gene: KCNK9: This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Fetal anomalies v5.16 KCNK3 Achchuthan Shanmugasundram commented on gene: KCNK3
Fetal anomalies v5.16 KCNJ6 Achchuthan Shanmugasundram commented on gene: KCNJ6
Fetal anomalies v5.16 KCNC3 Achchuthan Shanmugasundram commented on gene: KCNC3
Fetal anomalies v5.16 ITCH Achchuthan Shanmugasundram commented on gene: ITCH
Fetal anomalies v5.16 INTS13 Achchuthan Shanmugasundram commented on gene: INTS13
Fetal anomalies v5.16 INTS11 Achchuthan Shanmugasundram commented on gene: INTS11
Fetal anomalies v5.16 INPP5K Achchuthan Shanmugasundram commented on gene: INPP5K
Fetal anomalies v5.16 IL1RN Achchuthan Shanmugasundram commented on gene: IL1RN
Fetal anomalies v5.16 IDH2 Achchuthan Shanmugasundram commented on gene: IDH2
Fetal anomalies v5.16 HECTD4 Achchuthan Shanmugasundram commented on gene: HECTD4
Fetal anomalies v5.16 HEATR3 Achchuthan Shanmugasundram commented on gene: HEATR3
Fetal anomalies v5.16 GTPBP1 Achchuthan Shanmugasundram commented on gene: GTPBP1
Fetal anomalies v5.16 GPC4 Achchuthan Shanmugasundram commented on gene: GPC4
Fetal anomalies v5.16 GPAA1 Achchuthan Shanmugasundram commented on gene: GPAA1
Fetal anomalies v5.16 GON4L Achchuthan Shanmugasundram commented on gene: GON4L
Fetal anomalies v5.16 GNB2 Achchuthan Shanmugasundram commented on gene: GNB2: This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Fetal anomalies v5.16 GNAQ Achchuthan Shanmugasundram commented on gene: GNAQ
Fetal anomalies v5.16 GNAI1 Achchuthan Shanmugasundram commented on gene: GNAI1
Fetal anomalies v5.16 GNA14 Achchuthan Shanmugasundram commented on gene: GNA14
Fetal anomalies v5.16 GNA11 Achchuthan Shanmugasundram commented on gene: GNA11
Fetal anomalies v5.16 GLIS2 Achchuthan Shanmugasundram commented on gene: GLIS2
Fetal anomalies v5.16 GDF2 Achchuthan Shanmugasundram commented on gene: GDF2
Fetal anomalies v5.16 GALNT3 Achchuthan Shanmugasundram commented on gene: GALNT3
Fetal anomalies v5.16 FZD6 Achchuthan Shanmugasundram commented on gene: FZD6
Fetal anomalies v5.16 FZD5 Achchuthan Shanmugasundram commented on gene: FZD5
Fetal anomalies v5.16 FUZ Achchuthan Shanmugasundram commented on gene: FUZ
Fetal anomalies v5.16 FTO Achchuthan Shanmugasundram commented on gene: FTO
Fetal anomalies v5.16 FRYL Achchuthan Shanmugasundram commented on gene: FRYL
Fetal anomalies v5.16 FOXP4 Achchuthan Shanmugasundram commented on gene: FOXP4
Fetal anomalies v5.16 FOXI3 Achchuthan Shanmugasundram commented on gene: FOXI3
Fetal anomalies v5.16 FOSL2 Achchuthan Shanmugasundram commented on gene: FOSL2
Fetal anomalies v5.16 FN1 Achchuthan Shanmugasundram commented on gene: FN1
Fetal anomalies v5.16 FLCN Achchuthan Shanmugasundram commented on gene: FLCN
Fetal anomalies v5.16 FILIP1 Achchuthan Shanmugasundram commented on gene: FILIP1
Fetal anomalies v5.16 FGF23 Achchuthan Shanmugasundram commented on gene: FGF23
Fetal anomalies v5.16 FGF16 Achchuthan Shanmugasundram commented on gene: FGF16
Fetal anomalies v5.16 FERMT3 Achchuthan Shanmugasundram commented on gene: FERMT3
Fetal anomalies v5.16 FAS Achchuthan Shanmugasundram commented on gene: FAS
Fetal anomalies v5.16 EXPH5 Achchuthan Shanmugasundram commented on gene: EXPH5
Fetal anomalies v5.16 ESAM Achchuthan Shanmugasundram commented on gene: ESAM: This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Fetal anomalies v5.16 ERI1 Achchuthan Shanmugasundram commented on gene: ERI1
Fetal anomalies v5.16 ENG Achchuthan Shanmugasundram commented on gene: ENG
Fetal anomalies v5.16 EMILIN1 Achchuthan Shanmugasundram commented on gene: EMILIN1
Fetal anomalies v5.16 EMG1 Achchuthan Shanmugasundram commented on gene: EMG1
Fetal anomalies v5.16 EIF3B Achchuthan Shanmugasundram commented on gene: EIF3B
Fetal anomalies v5.16 EFEMP1 Achchuthan Shanmugasundram commented on gene: EFEMP1
Fetal anomalies v5.16 EFCAB1 Achchuthan Shanmugasundram commented on gene: EFCAB1
Fetal anomalies v5.16 DVL2 Achchuthan Shanmugasundram commented on gene: DVL2
Fetal anomalies v5.16 DRG1 Achchuthan Shanmugasundram commented on gene: DRG1
Fetal anomalies v5.16 DRC1 Achchuthan Shanmugasundram commented on gene: DRC1: This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Fetal anomalies v5.16 DPYSL5 Achchuthan Shanmugasundram commented on gene: DPYSL5: This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Fetal anomalies v5.16 DOHH Achchuthan Shanmugasundram commented on gene: DOHH: This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Fetal anomalies v5.16 DLX3 Achchuthan Shanmugasundram commented on gene: DLX3: This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Fetal anomalies v5.16 DLG5 Achchuthan Shanmugasundram commented on gene: DLG5: This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Fetal anomalies v5.16 DLG4 Achchuthan Shanmugasundram commented on gene: DLG4: This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Fetal anomalies v5.16 DHX30 Achchuthan Shanmugasundram commented on gene: DHX30: This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Fetal anomalies v5.16 DDRGK1 Achchuthan Shanmugasundram commented on gene: DDRGK1: This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Fetal anomalies v5.16 DCDC2 Achchuthan Shanmugasundram commented on gene: DCDC2: This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Fetal anomalies v5.16 DAW1 Achchuthan Shanmugasundram commented on gene: DAW1: This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Fetal anomalies v5.16 CYP2R1 Achchuthan Shanmugasundram commented on gene: CYP2R1: This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Fetal anomalies v5.16 CYP27B1 Achchuthan Shanmugasundram commented on gene: CYP27B1: This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Fetal anomalies v5.16 CYB5R3 Achchuthan Shanmugasundram commented on gene: CYB5R3: This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Fetal anomalies v5.16 CUL3 Achchuthan Shanmugasundram commented on gene: CUL3
Fetal anomalies v5.16 CTSC Achchuthan Shanmugasundram commented on gene: CTSC
Fetal anomalies v5.16 CSTA Achchuthan Shanmugasundram commented on gene: CSTA
Fetal anomalies v5.16 CSMD1 Achchuthan Shanmugasundram commented on gene: CSMD1
Fetal anomalies v5.16 CSGALNACT1 Achchuthan Shanmugasundram commented on gene: CSGALNACT1
Fetal anomalies v5.16 CRELD1 Achchuthan Shanmugasundram commented on gene: CRELD1
Fetal anomalies v5.16 COPB2 Achchuthan Shanmugasundram commented on gene: COPB2
Fetal anomalies v5.16 CNOT2 Achchuthan Shanmugasundram commented on gene: CNOT2
Fetal anomalies v5.16 CLPP Achchuthan Shanmugasundram commented on gene: CLPP
Fetal anomalies v5.16 CLCN5 Achchuthan Shanmugasundram commented on gene: CLCN5: This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Fetal anomalies v5.16 CHD8 Achchuthan Shanmugasundram commented on gene: CHD8
Fetal anomalies v5.16 CHD3 Achchuthan Shanmugasundram commented on gene: CHD3
Fetal anomalies v5.16 CEP295 Achchuthan Shanmugasundram commented on gene: CEP295
Fetal anomalies v5.16 CELSR3 Achchuthan Shanmugasundram commented on gene: CELSR3
Fetal anomalies v5.16 CDK10 Achchuthan Shanmugasundram commented on gene: CDK10
Fetal anomalies v5.16 CDH2 Achchuthan Shanmugasundram commented on gene: CDH2
Fetal anomalies v5.16 CD40LG Achchuthan Shanmugasundram commented on gene: CD40LG
Fetal anomalies v5.16 CD151 Achchuthan Shanmugasundram commented on gene: CD151
Fetal anomalies v5.16 CBY1 Achchuthan Shanmugasundram commented on gene: CBY1
Fetal anomalies v5.16 CASP2 Achchuthan Shanmugasundram commented on gene: CASP2
Fetal anomalies v5.16 CAPRIN1 Achchuthan Shanmugasundram commented on gene: CAPRIN1
Fetal anomalies v5.16 CAMTA1 Achchuthan Shanmugasundram commented on gene: CAMTA1
Fetal anomalies v5.16 CAMK2B Achchuthan Shanmugasundram commented on gene: CAMK2B
Fetal anomalies v5.16 CACNA1S Achchuthan Shanmugasundram commented on gene: CACNA1S
Fetal anomalies v5.16 CACHD1 Achchuthan Shanmugasundram commented on gene: CACHD1: This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Fetal anomalies v5.16 C1GALT1C1 Achchuthan Shanmugasundram commented on gene: C1GALT1C1
Fetal anomalies v5.16 C16orf62 Achchuthan Shanmugasundram commented on gene: C16orf62
Fetal anomalies v5.16 BPTF Achchuthan Shanmugasundram commented on gene: BPTF
Fetal anomalies v5.16 AXIN1 Achchuthan Shanmugasundram commented on gene: AXIN1
Fetal anomalies v5.16 ATG7 Achchuthan Shanmugasundram commented on gene: ATG7
Fetal anomalies v5.16 ASXL3 Achchuthan Shanmugasundram commented on gene: ASXL3
Fetal anomalies v5.16 ASPH Achchuthan Shanmugasundram commented on gene: ASPH
Fetal anomalies v5.16 ASCC3 Achchuthan Shanmugasundram commented on gene: ASCC3
Fetal anomalies v5.16 ARV1 Achchuthan Shanmugasundram commented on gene: ARV1: This gene and phenotype were reviewed during meetings between November 2024 & January 2025. The meetings included representatives of the Central & South and North Thames R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Stephanie Allen, Natalie Bibb, and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Sunayna Best, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Esther Kinning, Sahar Mansour, Soo-Mi Park, and Elizabeth Wall (R21 Clinical Oversight Group).
Fetal anomalies v5.16 AMOTL1 Achchuthan Shanmugasundram commented on gene: AMOTL1
Fetal anomalies v5.16 ALG5 Achchuthan Shanmugasundram commented on gene: ALG5
Fetal anomalies v5.16 ALG13 Achchuthan Shanmugasundram commented on gene: ALG13
Fetal anomalies v5.16 ALG11 Achchuthan Shanmugasundram commented on gene: ALG11
Fetal anomalies v5.16 AL117258.1 Achchuthan Shanmugasundram commented on gene: AL117258.1
Fetal anomalies v5.16 ADD1 Achchuthan Shanmugasundram commented on gene: ADD1
Fetal anomalies v5.16 ADAMTS15 Achchuthan Shanmugasundram commented on gene: ADAMTS15
Fetal anomalies v5.16 ACBD6 Achchuthan Shanmugasundram commented on gene: ACBD6
Fetal anomalies v5.16 ABCD4 Achchuthan Shanmugasundram commented on gene: ABCD4
Fetal anomalies v5.15 ZSCAN10 Vicki Harrison reviewed gene: ZSCAN10: Rating: AMBER; Mode of pathogenicity: ; Publications: 38386308; Phenotypes: Otofacial neurodevelopmental syndrome, MIM#620910; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 ZRSR2 Vicki Harrison reviewed gene: ZRSR2: Rating: GREEN; Mode of pathogenicity: ; Publications: 38158857; Phenotypes: Orofaciodigital syndrome, MONDO:0015375, ZRSR2-related; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v5.15 ZNF750 Vicki Harrison reviewed gene: ZNF750: Rating: RED; Mode of pathogenicity: ; Publications: 16751772; Phenotypes: Seborrhea-like dermatitis with psoriasiform elements, MIM#610227; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v5.15 ZNF687 Vicki Harrison reviewed gene: ZNF687: Rating: RED; Mode of pathogenicity: ; Publications: 29493781, 26849110; Phenotypes: Paget disease of bone 6, MIM#616833; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 ZNF423 Vicki Harrison reviewed gene: ZNF423: Rating: AMBER; Mode of pathogenicity: ; Publications: 39071699, 32925911, 33531950; Phenotypes: Joubert syndrome 19 / Nephronophthisis 14, MIM#614844; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v5.15 ZMYND8 Vicki Harrison reviewed gene: ZMYND8: Rating: AMBER; Mode of pathogenicity: ; Publications: 32530565, 35916866; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, ZMYND8-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 ZFX Vicki Harrison reviewed gene: ZFX: Rating: GREEN; Mode of pathogenicity: ; Publications: 38325380; Phenotypes: Intellectual developmental disorder, X-linked syndromic 37, MIM#301118; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Fetal anomalies v5.15 XPNPEP3 Vicki Harrison reviewed gene: XPNPEP3: Rating: AMBER; Mode of pathogenicity: ; Publications: 32660933, 20179356; Phenotypes: Nephronophthisis-like nephropathy 1, MIM#613159; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 WNT9B Vicki Harrison reviewed gene: WNT9B: Rating: AMBER; Mode of pathogenicity: ; Publications: 34145744; Phenotypes: Renal agenesis/hypoplasia/dysplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 WISP3 Anna de Burca reviewed gene: WISP3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Progressive pseudorheumatoid dysplasia, MIM#208230; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 WDR44 Vicki Harrison reviewed gene: WDR44: Rating: GREEN; Mode of pathogenicity: ; Publications: 38191484; Phenotypes: Ciliopathy, MONDO:0005308, WDR44-related; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v5.15 WBP4 Vicki Harrison reviewed gene: WBP4: Rating: GREEN; Mode of pathogenicity: ; Publications: 37963460, 37425688; Phenotypes: Neurodevelopmental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalities, MIM#620852; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 WASHC5 Vicki Harrison reviewed gene: WASHC5: Rating: GREEN; Mode of pathogenicity: ; Publications: 24065355; Phenotypes: Ritscher-Schinzel syndrome 1, MIM#220210; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 VHL Vicki Harrison reviewed gene: VHL: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: von Hippel-Lindau syndrome MIM#193300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v5.15 UQCC2 Sarah Graham reviewed gene: UQCC2: Rating: AMBER; Mode of pathogenicity: ; Publications: 24385928, 28804536; Phenotypes: Mitochondrial complex III deficiency, nuclear type 7, MIM#615824; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 UNC45A Sarah Graham reviewed gene: UNC45A: Rating: RED; Mode of pathogenicity: ; Publications: 29429573; Phenotypes: Osteootohepatoenteric syndrome, MIM#619377; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 UFSP2 Sarah Graham reviewed gene: UFSP2: Rating: GREEN; Mode of pathogenicity: ; Publications: 32755715, 33473208, 28892125, 26428751; Phenotypes: Spondyloepimetaphyseal dysplasia, Di Rocco type, MIM#617974, Beukes Hip Dysplasia, MIM#142669; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 U2AF2 Sarah Graham reviewed gene: U2AF2: Rating: GREEN; Mode of pathogenicity: ; Publications: 34112922, 36747105, 37092751, 37134193; Phenotypes: Developmental delay, dysmorphic facies, and brain anomalies MIM#620535; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 TYROBP Sarah Graham reviewed gene: TYROBP: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1, MIM#221770; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 TULP3 Sarah Graham reviewed gene: TULP3: Rating: RED; Mode of pathogenicity: ; Publications: 36276950, 30799239, 36460032, 30799240, 35397207; Phenotypes: Hepatorenocardiac degenerative fibrosis, MIM #619902; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 TUFM Sarah Graham reviewed gene: TUFM: Rating: AMBER; Mode of pathogenicity: ; Publications: 26741492, 17160893; Phenotypes: Combined oxidative phosphorylation deficiency 4, MIM#610678; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 TTC25 Samantha Doyle reviewed gene: TTC25: Rating: AMBER; Mode of pathogenicity: ; Publications: 27486780, 31765523, 34215651, 33746037, 33715250; Phenotypes: Ciliary dyskinesia, primary, 35, MIM#617092; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 TSHZ3 Sarah Graham reviewed gene: TSHZ3: Rating: GREEN; Mode of pathogenicity: ; Publications: 39420202, 34919690, 36553458; Phenotypes: Congenital anomaly of kidney and urinary tract; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 TRPM7 Sarah Graham reviewed gene: TRPM7: Rating: RED; Mode of pathogenicity: ; Publications: 31423533, 39621058, 35561741, 39099563, 35712613; Phenotypes: Amyotrophic lateral sclerosis-parkinsonism/dementia complex, susceptibility to, MIM#105500; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 TRIT1 Sarah Graham reviewed gene: TRIT1: Rating: GREEN; Mode of pathogenicity: ; Publications: 32088416, 36049610; Phenotypes: Combined oxidative phosphorylation deficiency 35, MIM#617873; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 TREM2 Sarah Graham reviewed gene: TREM2: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2, MIM#618193; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 TONSL Sarah Graham reviewed gene: TONSL: Rating: GREEN; Mode of pathogenicity: ; Publications: 32959051, 30773277, 30773278; Phenotypes: Spondyloepimetaphyseal dysplasia, sponastrime type, MIM#271510; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 TOMM7 Sarah Graham reviewed gene: TOMM7: Rating: AMBER; Mode of pathogenicity: ; Publications: 36299998, 36282599; Phenotypes: Garg-Mishra progeroid syndrome, MIM#620601; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 TOGARAM1 Sarah Graham reviewed gene: TOGARAM1: Rating: GREEN; Mode of pathogenicity: ; Publications: 32453716, 32747439; Phenotypes: Joubert syndrome 37, MIM#619185; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 TNRC6B Esther Kinning reviewed gene: TNRC6B: Rating: RED; Mode of pathogenicity: ; Publications: 32152250, 29463886; Phenotypes: Global developmental delay with speech and behavioral abnormalities, MIM#619243; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 TNFSF11 Sunayna Best reviewed gene: TNFSF11: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Osteopetrosis, autosomal recessive 2, MIM#259710; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 TNFRSF13B Sunayna Best reviewed gene: TNFRSF13B: Rating: RED; Mode of pathogenicity: ; Publications: 16007087, 16007086; Phenotypes: Immunodeficiency, common variable, 2, MIM#240500; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v5.15 THSD1 Sunayna Best reviewed gene: THSD1: Rating: GREEN; Mode of pathogenicity: ; Publications: 27895300, 33569873, 30055085, 37993095; Phenotypes: Lymphatic malformation 13, MIM#620244; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 TBR1 Sunayna Best reviewed gene: TBR1: Rating: GREEN; Mode of pathogenicity: ; Publications: 32005960; Phenotypes: Intellectual developmental disorder with autism and speech delay, MIM#606053; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 TAF8 Sunayna Best reviewed gene: TAF8: Rating: GREEN; Mode of pathogenicity: ; Publications: 39169228; Phenotypes: Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy, MIM#619972; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 TACR3 Sunayna Best reviewed gene: TACR3: Rating: RED; Mode of pathogenicity: ; Publications: 19079066, 20332248; Phenotypes: Hypogonadotropic hypogonadism 11 with or without anosmia, MIM#614840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 TAC3 Sunayna Best reviewed gene: TAC3: Rating: RED; Mode of pathogenicity: ; Publications: 20332248; Phenotypes: Hypogonadotropic hypogonadism 10 with or without anosmia, MIM#614839; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 STX5 Sunayna Best reviewed gene: STX5: Rating: AMBER; Mode of pathogenicity: ; Publications: 34711829; Phenotypes: Congenital disorder of glycosylation, type IIaa, MIM#620454; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 STAG1 Natalie Bibb reviewed gene: STAG1: Rating: RED; Mode of pathogenicity: ; Publications: 39224759, 34440290, 28119487; Phenotypes: Intellectual developmental disorder, autosomal dominant 47, MIM#617635; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Fetal anomalies v5.15 SPIN4 Sunayna Best reviewed gene: SPIN4: Rating: AMBER; Mode of pathogenicity: ; Publications: 36927955; Phenotypes: Lui-Jee-Baron syndrome, MIM#301114; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Fetal anomalies v5.15 SNUPN Sunayna Best reviewed gene: SNUPN: Rating: AMBER; Mode of pathogenicity: ; Publications: 38413582, 38366623; Phenotypes: Muscular dystrophy, limb-girdle, autosomal recessive 29, MIM#620793; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 SNRPE Sunayna Best reviewed gene: SNRPE: Rating: RED; Mode of pathogenicity: ; Publications: 33792916, 9621144; Phenotypes: Hypotrichosis 11, MIM#615059; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 SNF8 Sunayna Best reviewed gene: SNF8: Rating: GREEN; Mode of pathogenicity: ; Publications: 38423010; Phenotypes: Developmental and epileptic encephalopathy 115, MIM#620783, Neurodevelopmental disorder plus optic atrophy, MIM#620784; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 SNAP25 Sunayna Best reviewed gene: SNAP25: Rating: GREEN; Mode of pathogenicity: ; Publications: 36379720, 33299146; Phenotypes: Myasthenic syndrome, congenital, 18, MIM#616330; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 SMPD1 Natalie Chandler reviewed gene: SMPD1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Niemann-Pick disease, type A, MIM#257200, Niemann-Pick disease, type B, MIM#607616; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 SMOC2 Sunayna Best reviewed gene: SMOC2: Rating: RED; Mode of pathogenicity: ; Publications: 22152679, 23317772; Phenotypes: Dentin dysplasia, type I, with microdontia and misshapen teeth, MIM#125400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 SLCO2A1 Stephanie Allen reviewed gene: SLCO2A1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: PHOAR2-enteropathy syndrome, MIM#614441, Hypertrophic osteoarthropathy, primary, autosomal dominant, MIM#167100; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v5.15 SLC4A10 Stephanie Allen reviewed gene: SLC4A10: Rating: GREEN; Mode of pathogenicity: ; Publications: 31130284, 37459438, 38054405; Phenotypes: Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, MIM#620746; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 SLC35A1 Stephanie Allen reviewed gene: SLC35A1: Rating: AMBER; Mode of pathogenicity: ; Publications: 30115659, 28856833; Phenotypes: Congenital disorder of glycosylation, type IIf, MIM#603585; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 SLC34A3 Stephanie Allen reviewed gene: SLC34A3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Hypophosphatemic rickets with hypercalciuria, MIM#241530; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 SLC34A1 Stephanie Allen reviewed gene: SLC34A1: Rating: GREEN; Mode of pathogenicity: ; Publications: 9560283, 25050900, 12324554; Phenotypes: Infantile hypercalcemia-2, MIM#616963; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 SLC30A7 Stephanie Allen reviewed gene: SLC30A7: Rating: AMBER; Mode of pathogenicity: ; Publications: 36821639; Phenotypes: Ziegler-Huang syndrome, MIM#620501; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 SLC25A4 Stephanie Allen reviewed gene: SLC25A4: Rating: GREEN; Mode of pathogenicity: ; Publications: 27693233, 30013777; Phenotypes: Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD, MIM#617184; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 SLC24A4 Stephanie Allen reviewed gene: SLC24A4: Rating: RED; Mode of pathogenicity: ; Publications: 24621671, 23375655; Phenotypes: Amelogenesis imperfecta, type IIA5, MIM#615887; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 SIAH1 Esther Kinning reviewed gene: SIAH1: Rating: AMBER; Mode of pathogenicity: ; Publications: 32430360; Phenotypes: Buratti-Harel syndrome, MIM#619314; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 SHROOM4 Stephanie Allen reviewed gene: SHROOM4: Rating: RED; Mode of pathogenicity: ; Publications: 32565546, 36379543; Phenotypes: Abnormal corpus callosum; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v5.15 SHROOM3 Stephanie Allen reviewed gene: SHROOM3: Rating: AMBER; Mode of pathogenicity: ; Publications: 32621286; Phenotypes: Neural tube defect; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v5.15 SH3BP2 Stephanie Allen reviewed gene: SH3BP2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Cherubism, MIM#118400; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 SGMS2 Stephanie Allen reviewed gene: SGMS2: Rating: RED; Mode of pathogenicity: ; Publications: 30779713, 32028018; Phenotypes: Calvarial doughnut lesions with bone fragility with or without spondylometaphyseal dysplasia, MIM#126550; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 SFRP4 Stephanie Allen reviewed gene: SFRP4: Rating: RED; Mode of pathogenicity: ; Publications: 24096177, 22387305, 28100910, 20174869, 27117872, 22965941, 27355534, 26273529; Phenotypes: Pyle disease, MIM#265900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 SETD1A Stephanie Allen reviewed gene: SETD1A: Rating: GREEN; Mode of pathogenicity: ; Publications: 37000069; Phenotypes: Neurodevelopmental disorder with speech impairment and dysmorphic facies, MIM#619056; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v5.15 SCYL2 Soo-Mi Park reviewed gene: SCYL2: Rating: GREEN; Mode of pathogenicity: ; Publications: 39138116, 39169672; Phenotypes: Arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum, MIM#618766; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 SASS6 Soo-Mi Park reviewed gene: SASS6: Rating: GREEN; Mode of pathogenicity: ; Publications: 38501757, 24951542, 30639237, 36739862; Phenotypes: Microcephaly 14, primary, autosomal recessive, MIM#616402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 RSPRY1 Soo-Mi Park reviewed gene: RSPRY1: Rating: GREEN; Mode of pathogenicity: ; Publications: 30063090, 38562122, 26365341; Phenotypes: Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type, MIM#616723; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 RSPO2 Soo-Mi Park reviewed gene: RSPO2: Rating: GREEN; Mode of pathogenicity: ; Publications: 32457899, 29769720; Phenotypes: Tetraamelia syndrome 2, MIM#618021; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 RRAS Soo-Mi Park reviewed gene: RRAS: 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: 24705357, 32815881, 34935735; Phenotypes: Noonan syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v5.15 RRAGC Soo-Mi Park reviewed gene: RRAGC: Rating: GREEN; Mode of pathogenicity: ; Publications: 37057673, 27234373; Phenotypes: Long-Olsen-Distelmaier syndrome, MIM#620609; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 RPL13 Soo-Mi Park reviewed gene: RPL13: Rating: GREEN; Mode of pathogenicity: ; Publications: 31630789; Phenotypes: Spondyloepimetaphyseal dysplasia, Isidor-Toutain type, MIM#618728; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v5.15 ROBO2 Soo-Mi Park reviewed gene: ROBO2: Rating: RED; Mode of pathogenicity: ; Publications: 34059960, 24429398, 17357069, 26026792, 19350278, 18235093, 29194579; Phenotypes: Vesicoureteral reflux 2, MIM#610878; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 ROBO1 Sarah Graham reviewed gene: ROBO1: Rating: GREEN; Mode of pathogenicity: ; Publications: 35227688, 28286008, 29194579; Phenotypes: Neurooculorenal syndrome, MIM#620305; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 RNU4-2 Soo-Mi Park reviewed gene: RNU4-2: Rating: GREEN; Mode of pathogenicity: ; Publications: 38991538, 38821540, 38859706; Phenotypes: ReNU syndrome, MIM#620851; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 RINT1 Soo-Mi Park reviewed gene: RINT1: Rating: AMBER; Mode of pathogenicity: ; Publications: 31204009; Phenotypes: Infantile liver failure syndrome 3, MIM#618641; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 RFWD3 Soo-Mi Park reviewed gene: RFWD3: Rating: GREEN; Mode of pathogenicity: ; Publications: 38058754, 2869192; Phenotypes: Fanconi anemia, complementation group W, MIM#617784; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 RASGRP2 Soo-Mi Park reviewed gene: RASGRP2: Rating: RED; Mode of pathogenicity: ; Publications: 18709451, 24958846; Phenotypes: Bleeding disorder, platelet-type, 18, MIM#615888; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 RAP1B Soo-Mi Park reviewed gene: RAP1B: 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: 37850357, 35451551, 32627184; Phenotypes: Thrombocytopenia 11 with multiple congenital anomalies and dysmorphic facies, MIM#620654; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 RAB34 Soo-Mi Park reviewed gene: RAB34: Rating: GREEN; Mode of pathogenicity: ; Publications: 37619988, 37384395; Phenotypes: Orofaciodigital syndrome XX, MIM#620718; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 PUM1 Soo-Mi Park reviewed gene: PUM1: Rating: GREEN; Mode of pathogenicity: ; Publications: 25768905, 30903679, 29474920, 31859446, 35386260; Phenotypes: Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM#620719; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 PSMF1 Sarah Graham reviewed gene: PSMF1: Rating: GREEN; Mode of pathogenicity: ; Publications: 39148840; Phenotypes: Complex neurodevelopmental disorder with motor features, MONDO:0100516, PSMF1-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 PSMC3 Sarah Graham reviewed gene: PSMC3: Rating: AMBER; Mode of pathogenicity: ; Publications: 37256937; Phenotypes: Neurodevelopmental disorder, MONDO:0700092; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 PSMB9 Sarah Graham reviewed gene: PSMB9: Rating: RED; Mode of pathogenicity: ; Publications: 33727065, 34819510; Phenotypes: Proteasome-associated autoinflammatory syndrome 6, MIM#620796; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 PRKG2 Sarah Graham reviewed gene: PRKG2: Rating: AMBER; Mode of pathogenicity: ; Publications: 34680883, 33106379, 34782440; Phenotypes: Spondylometaphyseal dysplasia, Pagnamenta type, MIM#619638, Acromesomelic dysplasia 4, MIM#619636; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 PRKCSH Sarah Graham reviewed gene: PRKCSH: Rating: RED; Mode of pathogenicity: ; Publications: 24886261, 12529853, 12577059; Phenotypes: Polycystic liver disease 1 with or without kidney cysts, MIM#174050; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 PLS3 Sarah Graham reviewed gene: PLS3: 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: 24088043, 37751738, 29736964, 25209159, 32655496, 28777485, 29884797; Phenotypes: Diaphragmatic hernia 5, X-linked, MIM#306950; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Fetal anomalies v5.15 PLD1 Sarah Graham reviewed gene: PLD1: Rating: AMBER; Mode of pathogenicity: ; Publications: 33645542, 27799408; Phenotypes: Cardiac valvular dysplasia 1, MIM#212093; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 PKDCC Sarah Graham reviewed gene: PKDCC: Rating: GREEN; Mode of pathogenicity: ; Publications: 30478137, 19097194; Phenotypes: Rhizomelic limb shortening with dysmorphic features, MIM#618821; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 PISD Sarah Graham reviewed gene: PISD: Rating: AMBER; Mode of pathogenicity: ; Publications: 31263216, 30858161, 30488656, 3561949; Phenotypes: Liberfarb syndrome, MIM#618889; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 PIP5K1C Sarah Graham reviewed gene: PIP5K1C: Rating: GREEN; Mode of pathogenicity: ; Publications: 17701898, 38491417; Phenotypes: Lethal congenital contractural syndrome 3, MIM#611369; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 PIGY Sarah Graham reviewed gene: PIGY: Rating: AMBER; Mode of pathogenicity: ; Publications: 26293662, 38790248; Phenotypes: Hyperphosphatasia with impaired intellectual development syndrome 6, MIM#616809; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 PIGS Sarah Graham reviewed gene: PIGS: Rating: GREEN; Mode of pathogenicity: ; Publications: 33410539, 37035392; Phenotypes: Developmental and epileptic encephalopathy 95, MIM#618143; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 PIGG Sarah Graham reviewed gene: PIGG: Rating: AMBER; Mode of pathogenicity: ; Publications: 34113002, 26996948; Phenotypes: Neurodevelopmental disorder with or without hypotonia, seizures, and cerebellar atrophy, MIM#616917; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 PI4K2A Sarah Graham reviewed gene: PI4K2A: Rating: GREEN; Mode of pathogenicity: ; Publications: 30564627, 35880319, 32418222; Phenotypes: Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities, MIM#620732; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 PHLDB1 Sarah Graham reviewed gene: PHLDB1: Rating: AMBER; Mode of pathogenicity: ; Publications: 36543534; Phenotypes: Osteogenesis imperfecta, type XXIII, MIM#620639; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 PAN2 Samantha Doyle reviewed gene: PAN2: Rating: GREEN; Mode of pathogenicity: ; Publications: 29620724, 35304602; Phenotypes: Syndromic disease MONDO:0002254; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 NUP214 Esther Kinning reviewed gene: NUP214: Rating: AMBER; Mode of pathogenicity: ; Publications: 31178128, 38179855, 30758658, 3965093; Phenotypes: Encephalopathy, acute, infection-induced, susceptibility to, 9, MIM#618426; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 NUDT2 Samantha Doyle reviewed gene: NUDT2: Rating: GREEN; Mode of pathogenicity: ; Publications: 38141063; Phenotypes: Intellectual developmental disorder with or without peripheral neuropathy, MIM#619844; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 NUAK2 Samantha Doyle reviewed gene: NUAK2: Rating: RED; Mode of pathogenicity: ; Publications: 32845958; Phenotypes: Anencephaly 2, MIM#619452; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 NSUN6 Samantha Doyle reviewed gene: NSUN6: Rating: GREEN; Mode of pathogenicity: ; Publications: 37226891; Phenotypes: Intellectual developmental disorder, autosomal recessive 82, MIM#620779; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 NSUN2 Samantha Doyle reviewed gene: NSUN2: Rating: RED; Mode of pathogenicity: ; Publications: 38643142, 37305761, 33002343, 36420349; Phenotypes: Intellectual developmental disorder, autosomal recessive 5, MIM#611091; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 NPR3 Samantha Doyle reviewed gene: NPR3: Rating: RED; Mode of pathogenicity: ; Publications: 30032985, 10468599; Phenotypes: Boudin-Mortier syndrome, MIM#619543; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 NPNT Samantha Doyle reviewed gene: NPNT: Rating: AMBER; Mode of pathogenicity: ; Publications: 17537792, 35246978, 34049960; Phenotypes: Renal agenesis, MONDO:0018470, NPNT-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 NLRP3 Samantha Doyle reviewed gene: NLRP3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: CINCA syndrome, MIM#607115; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 NHP2 Samantha Doyle reviewed gene: NHP2: Rating: AMBER; Mode of pathogenicity: ; Publications: 18523010; Phenotypes: Dyskeratosis congenita, autosomal recessive 2, MIM#613987; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 NARS Samantha Doyle reviewed gene: NARS: Rating: RED; Mode of pathogenicity: ; Publications: 32738225, 32788587; Phenotypes: Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, autosomal recessive, MIM#619091, Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, autosomal dominant, MIM#619092; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v5.15 MSTO1 Sarah Graham reviewed gene: MSTO1: Rating: GREEN; Mode of pathogenicity: ; Publications: 28554942, 31463572, 29339779, 28544275, 30684668; Phenotypes: Myopathy, mitochondrial, and ataxia, MIM#617675; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 MMP2 Samantha Doyle reviewed gene: MMP2: Rating: AMBER; Mode of pathogenicity: ; Publications: 16542393; Phenotypes: Multicentric osteolysis, nodulosis, and arthropathy, MIM#259600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 MMP15 Samantha Doyle reviewed gene: MMP15: Rating: AMBER; Mode of pathogenicity: ; Publications: 34988996, 33875846; Phenotypes: Cholestasis, congenital heart disease; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 MIR17HG Sahar Mansour reviewed gene: MIR17HG: Rating: AMBER; Mode of pathogenicity: ; Publications: 36588757, 26360630, 30672094, 33818875; Phenotypes: Feingold syndrome; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v5.15 MDFIC Sahar Mansour reviewed gene: MDFIC: Rating: GREEN; Mode of pathogenicity: ; Publications: 35235341; Phenotypes: Lymphatic malformation 12, MIM#620014; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 MBOAT7 Sahar Mansour reviewed gene: MBOAT7: Rating: AMBER; Mode of pathogenicity: ; Publications: 31852446, 38407511, 37628684, 33335874, 32645526, 34979703, 38088234, 32744787, 36672789; Phenotypes: Intellectual developmental disorder, autosomal recessive 57, MIM#617188; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 MAX Sahar Mansour reviewed gene: MAX: Rating: GREEN; Mode of pathogenicity: ; Publications: 38141607; Phenotypes: Polydactyly-macrocephaly syndrome, MIM#620712; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 MAPKBP1 Sahar Mansour reviewed gene: MAPKBP1: Rating: RED; Mode of pathogenicity: ; Publications: 28089251; Phenotypes: Nephronophthisis 20, MIM#617271; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 MAP4K4 Sahar Mansour reviewed gene: MAP4K4: Rating: GREEN; Mode of pathogenicity: ; Publications: 37126546; Phenotypes: RASopathy, MONDO:0021060, MAP4K4-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 LSM11 Natalie Bibb reviewed gene: LSM11: Rating: AMBER; Mode of pathogenicity: ; Publications: 33230297; Phenotypes: Aicardi-Goutieres syndrome 8, MIM#619486; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 LRRK1 Sahar Mansour reviewed gene: LRRK1: Rating: AMBER; Mode of pathogenicity: ; Publications: 32119750, 27055475, 31571209, 27829680; Phenotypes: Osteosclerotic metaphyseal dysplasia (OSMD), MIM#615198; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 LRIG2 Sahar Mansour reviewed gene: LRIG2: Rating: AMBER; Mode of pathogenicity: ; Publications: 27855655, 30885509, 23313374; Phenotypes: Urofacial syndrome 2, MIM#615112; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 LRBA Sahar Mansour reviewed gene: LRBA: Rating: RED; Mode of pathogenicity: ; Publications: 25468195, 22721650, 22608502, 22981790, 26206937; Phenotypes: Immunodeficiency, common variable, 8, with autoimmunity, MIM#614700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 LRAT Sahar Mansour reviewed gene: LRAT: Rating: RED; Mode of pathogenicity: ; Publications: 18055821, 17011878, 11381255; Phenotypes: Leber congenital amaurosis 14,MIM#613341; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 LPIN2 Sahar Mansour reviewed gene: LPIN2: Rating: RED; Mode of pathogenicity: ; Publications: 29912021; Phenotypes: Majeed syndrome, MIM#609628; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 LOX Sahar Mansour reviewed gene: LOX: Rating: GREEN; Mode of pathogenicity: ; Publications: 33866545, 31742715; Phenotypes: Aortic aneurysm, familial thoracic 10, MIM#617168; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 LNPK Sahar Mansour reviewed gene: LNPK: Rating: GREEN; Mode of pathogenicity: ; Publications: 30032983, 35599435, 37794925; Phenotypes: Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum, MIM#618090; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 LIPT2 Sahar Mansour reviewed gene: LIPT2: Rating: GREEN; Mode of pathogenicity: ; Publications: 28757203, 39536593; Phenotypes: Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities, MIM#617668; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 LIPN Natalie Chandler reviewed gene: LIPN: Rating: RED; Mode of pathogenicity: ; Publications: 21439540; Phenotypes: Ichthyosis, congenital, autosomal recessive 8, MIM#613943; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 LINS1 Natalie Chandler reviewed gene: LINS1: Rating: AMBER; Mode of pathogenicity: ; Publications: 32802957, 28181389, 38563234, 32499722, 31922598, 39138116, 34450347; Phenotypes: Intellectual developmental disorder, autosomal recessive 27, MIM#614340; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 LAMB2 Esther Kinning reviewed gene: LAMB2: Rating: GREEN; Mode of pathogenicity: ; Publications: 14136829, 15372515, 17256789; Phenotypes: Pierson syndrome, MIM#609049; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 LAMA5 Sarah Graham reviewed gene: LAMA5: Rating: GREEN; Mode of pathogenicity: ; Publications: 32439764, 35419533, 35584218, 36714636, 37985485; Phenotypes: Nephrotic syndrome, type 26, MIM#620049; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 KPTN Natalie Chandler reviewed gene: KPTN: Rating: AMBER; Mode of pathogenicity: ; Publications: 39083632; Phenotypes: Intellectual developmental disorder, autosomal recessive 41, MIM#615637; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 KMT2B Natalie Bibb reviewed gene: KMT2B: Rating: GREEN; Mode of pathogenicity: ; Publications: 29276005, 33150406, 29697234; Phenotypes: Intellectual developmental disorder, autosomal dominant 68, MIM#619934; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 KIF5B Natalie Chandler reviewed gene: KIF5B: Rating: GREEN; Mode of pathogenicity: ; Publications: 35342932, 36018820; Phenotypes: Kyphomelic dysplasia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 KIF26A Natalie Chandler reviewed gene: KIF26A: Rating: GREEN; Mode of pathogenicity: ; Publications: 36564622; Phenotypes: Cortical dysplasia, complex, with other brain malformations 11, MIM#620156; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 KIF24 Natalie Chandler reviewed gene: KIF24: Rating: GREEN; Mode of pathogenicity: ; Publications: 35748595; Phenotypes: Skeletal dysplasia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 KDR Esther Kinning reviewed gene: KDR: Rating: AMBER; Mode of pathogenicity: ; Publications: 30232381, 34113005, 28991257; Phenotypes: Hemangioma, capillary infantile, somatic, MIM#602089; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 KDM5A Natalie Chandler reviewed gene: KDM5A: Rating: AMBER; Mode of pathogenicity: ; Publications: 33350388, 21937992; Phenotypes: El Hayek-Chahrour neurodevelopmental syndrome, MIM#620820; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v5.15 KDM2B Natalie Chandler reviewed gene: KDM2B: Rating: GREEN; Mode of pathogenicity: ; Publications: 36322151; Phenotypes: Neurodevelopmental disorder MONDO#0700092, KDM2B-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 KDELR2 Natalie Chandler reviewed gene: KDELR2: Rating: GREEN; Mode of pathogenicity: ; Publications: 33053334; Phenotypes: Osteogenesis imperfecta, type XXI, MIM#619131; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 KCNT1 Natalie Chandler reviewed gene: KCNT1: Rating: AMBER; 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: 36307859; Phenotypes: Developmental and epileptic encephalopathy 14, MIM#614959; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 KCNN3 Natalie Chandler reviewed gene: KCNN3: Rating: AMBER; 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: 33594261, 31155282; Phenotypes: Zimmermann-Laband syndrome 3, MIM#618658; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 KCNK9 Natalie Chandler reviewed gene: KCNK9: Rating: AMBER; Mode of pathogenicity: ; Publications: 36307859; Phenotypes: Birk-Barel syndrome, MIM#612292; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Fetal anomalies v5.15 KCNK3 Natalie Chandler reviewed gene: KCNK3: 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: 36195757; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, KCNK3-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 KCNJ6 Natalie Chandler reviewed gene: KCNJ6: Rating: RED; 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: 34964963, 25620207, 36071510, 29852244; Phenotypes: Keppen-Lubinsky syndrome, MIM#614098; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 KCNC3 Natalie Canham reviewed gene: KCNC3: Rating: GREEN; Mode of pathogenicity: ; Publications: 20301404; Phenotypes: Spinocerebellar ataxia 13, MIM#605259; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 ITCH Natalie Canham reviewed gene: ITCH: Rating: RED; Mode of pathogenicity: ; Publications: 20170897, 31091003; Phenotypes: Autoimmune disease, multisystem, with facial dysmorphism, MIM#613385; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 INTS13 Natalie Canham reviewed gene: INTS13: Rating: AMBER; Mode of pathogenicity: ; Publications: 36229431; Phenotypes: Oral-facial-digital syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 INTS11 Natalie Canham reviewed gene: INTS11: Rating: GREEN; Mode of pathogenicity: ; Publications: 39030370, 37054711; Phenotypes: Neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities, MIM#620428; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 INPP5K Natalie Canham reviewed gene: INPP5K: Rating: AMBER; Mode of pathogenicity: ; Publications: 33193651, 31630891, 28940338, 28190459, 28190456; Phenotypes: Muscular dystrophy, congenital, with cataracts and intellectual disability, MIM#617404; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 IL1RN Natalie Canham reviewed gene: IL1RN: Rating: RED; Mode of pathogenicity: ; Publications: 19494218, 19494219; Phenotypes: Interleukin 1 receptor antagonist deficiency, MIM#612852; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 IDH2 Natalie Canham reviewed gene: IDH2: Rating: RED; Mode of pathogenicity: ; Publications: 20847235, 38782764; Phenotypes: D-2-hydroxyglutaric aciduria 2, MIM#613657; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v5.15 HECTD4 Natalie Canham reviewed gene: HECTD4: Rating: GREEN; Mode of pathogenicity: ; Publications: 36401616; Phenotypes: Neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosum, MIM#620250; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 HEATR3 Natalie Canham reviewed gene: HEATR3: Rating: RED; Mode of pathogenicity: ; Publications: 35213692; Phenotypes: Diamond-Blackfan anemia 21, MIM#620072; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 GTPBP1 Natalie Canham reviewed gene: GTPBP1: Rating: AMBER; Mode of pathogenicity: ; Publications: 38118446; Phenotypes: Neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1, MIM#620888; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 GPC4 Esther Kinning reviewed gene: GPC4: Rating: AMBER; Mode of pathogenicity: ; Publications: 21567928, 30982611, 4708024, 18541962, 12605449, 9001804, 17726694; Phenotypes: Keipert syndrome, MIM#301026; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v5.15 GPAA1 Natalie Canham reviewed gene: GPAA1: Rating: RED; Mode of pathogenicity: ; Publications: 29100095, 37510348, 34703884, 39152716; Phenotypes: Glycosylphosphatidylinositol biosynthesis defect 15, MIM#617810; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 GON4L Anna de Burca reviewed gene: GON4L: Rating: GREEN; Mode of pathogenicity: ; Publications: 39500882; Phenotypes: Growth impairment, microcephaly, situs inversus, developmental delay; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 GNB2 Natalie Canham reviewed gene: GNB2: Rating: GREEN; Mode of pathogenicity: ; Publications: 31698099, 36658419, 34183358; Phenotypes: Neurodevelopmental disorder with hypotonia and dysmorphic facies, MIM#619503; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 GNAQ Natalie Canham reviewed gene: GNAQ: Rating: RED; Mode of pathogenicity: ; Publications: 37606556, 23656586, 36263782; Phenotypes: Capillary malformations, congenital, 1, somatic, mosaic, MIM#163000, Sturge-Weber syndrome, somatic, mosaic, MIM#185300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v5.15 GNAI1 Natalie Canham reviewed gene: GNAI1: Rating: RED; Mode of pathogenicity: ; Publications: 34685729, 34819662, 39083633, 38441201, 33473207; Phenotypes: Neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities, MIM#619854; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v5.15 GNA14 Natalie Bibb reviewed gene: GNA14: Rating: AMBER; Mode of pathogenicity: ; Publications: 38917801; Phenotypes: Congenital vascular tumours; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v5.15 GNA11 Natalie Bibb reviewed gene: GNA11: Rating: AMBER; Mode of pathogenicity: ; Publications: 27438697; Phenotypes: Hypocalciuric hypercalcemia, type II, MIM#145981, Hypocalcemia, autosomal dominant 2, MIM#615361; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v5.15 GLIS2 Natalie Bibb reviewed gene: GLIS2: Rating: RED; Mode of pathogenicity: ; Publications: 31676329, 17618285, 23559409; Phenotypes: Nephronophthisis 7, MIM#611498; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 GDF2 Natalie Bibb reviewed gene: GDF2: Rating: AMBER; Mode of pathogenicity: ; Publications: 32618121; Phenotypes: Telangiectasia, hereditary hemorrhagic, type 5, MIM#615506; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 GALNT3 Natalie Bibb reviewed gene: GALNT3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Tumoral calcinosis, hyperphosphatemic, familial 1, MIM#211900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 FZD6 Natalie Bibb reviewed gene: FZD6: Rating: AMBER; Mode of pathogenicity: ; Publications: 28425981, 26036949, 33082562; Phenotypes: Nail disorder, nonsyndromic congenital, 1, MIM#161050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 FZD5 Natalie Bibb reviewed gene: FZD5: Rating: RED; Mode of pathogenicity: ; Publications: 32737437, 36695497, 26908622, 33633439; Phenotypes: Microphthalmia/coloboma 11, MIM#620731; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 FUZ Natalie Bibb reviewed gene: FUZ: Rating: GREEN; Mode of pathogenicity: ; Publications: 29068549, 34719684, 38702430; Phenotypes: Skeletal ciliopathy, MONDO:0005308; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 FTO Natalie Bibb reviewed gene: FTO: Rating: GREEN; Mode of pathogenicity: ; Publications: 19559399, 19234441, 26697951, 26378117, 26740239; Phenotypes: Growth retardation, developmental delay, facial dysmorphism, MIM#612938; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 FRYL Natalie Bibb reviewed gene: FRYL: Rating: AMBER; Mode of pathogenicity: ; Publications: 38479391; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, FRYL-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 FOXP4 Natalie Bibb reviewed gene: FOXP4: Rating: GREEN; Mode of pathogenicity: ; Publications: 33110267, 36301021; Phenotypes: Neurodevelopmental disorder, congenital diaphragmatic hernia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v5.15 FOXI3 Anna de Burca reviewed gene: FOXI3: Rating: AMBER; Mode of pathogenicity: ; Publications: 36260083, 37041148, 25655429; Phenotypes: Craniofacial microsomia 2, MIM#620444; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v5.15 FOSL2 Anna de Burca reviewed gene: FOSL2: Rating: GREEN; Mode of pathogenicity: ; Publications: 36197437; Phenotypes: Aplasia cutis-enamel dysplasia syndrome, MIM#620789; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 FN1 Anna de Burca reviewed gene: FN1: Rating: GREEN; Mode of pathogenicity: ; Publications: 32200603; Phenotypes: Spondylometaphyseal dysplasia, corner fracture type, MIM#184255; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v5.15 FLCN Anna de Burca reviewed gene: FLCN: Rating: RED; Mode of pathogenicity: ; Publications: 19785621, 31266032; Phenotypes: Pneumothorax, primary spontaneous, MIM#173600, Birt-Hogg-Dube syndrome, MIM#135150; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 FILIP1 Anna de Burca reviewed gene: FILIP1: Rating: GREEN; Mode of pathogenicity: ; Publications: 36943452, 37163662; Phenotypes: Neuromuscular disorder, congenital, with dysmorphic facies, MIM#620775; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 FGF23 Sarah Graham reviewed gene: FGF23: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: Hypophosphatemic rickets, autosomal dominant, MIM#6193100, Tumoral calcinosis, hyperphosphatemic, familial, MIM#6211900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 FGF16 Sarah Graham reviewed gene: FGF16: Rating: AMBER; Mode of pathogenicity: ; Publications: 24706454, 23709756, 25333065; Phenotypes: Metacarpal 4-5 fusion, MIM#309630; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v5.15 FERMT3 Sarah Graham reviewed gene: FERMT3: Rating: RED; Mode of pathogenicity: ; Publications: 19064721, 19234460; Phenotypes: Leukocyte adhesion deficiency, type III, MIM#612840; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 FAS Sarah Graham reviewed gene: FAS: Rating: GREEN; Mode of pathogenicity: ; Publications: 39384643; Phenotypes: Autoimmune lymphoproliferative syndrome, type IA, MIM#601859; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v5.15 EXPH5 Natalie Chandler reviewed gene: EXPH5: Rating: RED; Mode of pathogenicity: ; Publications: 32176379, 27730671, 23176819, 24443915, 24005056, 27384765; Phenotypes: Epidermolysis bullosa simplex 4, localized or generalized intermediate, autosomal recessive, MIM#615028; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 ESAM Natalie Chandler reviewed gene: ESAM: Rating: GREEN; Mode of pathogenicity: ; Publications: 36996813, 39414991; Phenotypes: Neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity, MIM#620371; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 ERI1 Natalie Chandler reviewed gene: ERI1: Rating: GREEN; Mode of pathogenicity: ; Publications: 37352860, 36208065, 33942433, 28488351; Phenotypes: Spondyloepimetaphyseal dysplasia, Guo-Campeau type, MIM#620663, Hoxha-Aliu syndrome, MIM#620662; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 ENG Natalie Chandler reviewed gene: ENG: Rating: GREEN; Mode of pathogenicity: ; Publications: 36588762, 15520401, 32954511; Phenotypes: Telangiectasia, hereditary hemorrhagic, type 1, MIM#187300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 EMILIN1 Natalie Chandler reviewed gene: EMILIN1: Rating: AMBER; Mode of pathogenicity: ; Publications: 36351433, 14701737; Phenotypes: Arterial tortuosity-bone fragility syndrome, MIM#620908; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 EMG1 Esther Kinning reviewed gene: EMG1: Rating: GREEN; Mode of pathogenicity: ; Publications: 19463982; Phenotypes: Bowen-Conradi syndrome, MIM#211180; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 EIF3B Esther Kinning reviewed gene: EIF3B: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Tetralogy of Fallot, bilateral cleft lip and palate, single kidney, asplenia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 EFEMP1 Esther Kinning reviewed gene: EFEMP1: Rating: AMBER; Mode of pathogenicity: ; Publications: 17872905, 32006683, 33807164, 31792352, 22489068; Phenotypes: Cutis laxa, autosomal recessive, type ID, MIM#620780; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 EFCAB1 Elizabeth Scotchman reviewed gene: EFCAB1: Rating: GREEN; Mode of pathogenicity: ; Publications: 36727596; Phenotypes: Ciliary dyskinesia, primary, 53, MIM#620642; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 DVL2 Esther Kinning reviewed gene: DVL2: Rating: AMBER; Mode of pathogenicity: ; Publications: 33599851, 35047859, 30521570; Phenotypes: Robinow syndrome, MONDO:0019978; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 DRG1 Esther Kinning reviewed gene: DRG1: Rating: GREEN; Mode of pathogenicity: ; Publications: 37179472; Phenotypes: Tan-Almurshedi syndrome, MIM#620641; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 DRC1 Achchuthan Shanmugasundram reviewed gene: DRC1: Rating: AMBER; Mode of pathogenicity: ; Publications: 39462806, 34851034, 39152285; Phenotypes: Ciliary dyskinesia, primary, 21, MIM#615294; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 DPYSL5 Achchuthan Shanmugasundram reviewed gene: DPYSL5: Rating: GREEN; Mode of pathogenicity: ; Publications: 33894126; Phenotypes: Ritscher-Schinzel syndrome 4, MIM#619435; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 DOHH Achchuthan Shanmugasundram reviewed gene: DOHH: Rating: AMBER; Mode of pathogenicity: ; Publications: 35858628; Phenotypes: Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment, MIM#620066; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 DLX3 Achchuthan Shanmugasundram reviewed gene: DLX3: Rating: RED; Mode of pathogenicity: ; Publications: 26104267, 26762616; Phenotypes: Amelogenesis imperfecta, type IV, MIM#104510, Trichodontoosseous syndrome, MIM#190320; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 DLG5 Achchuthan Shanmugasundram reviewed gene: DLG5: Rating: GREEN; Mode of pathogenicity: ; Publications: 30791088, 32631816; Phenotypes: Yuksel-Vogel-Bauser syndrome, MIM#620703; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 DLG4 Achchuthan Shanmugasundram reviewed gene: DLG4: Rating: AMBER; Mode of pathogenicity: ; Publications: 37347881; Phenotypes: Intellectual developmental disorder, autosomal dominant 62, MIM#618793; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 DHX30 Achchuthan Shanmugasundram reviewed gene: DHX30: Rating: GREEN; Mode of pathogenicity: ; Publications: 38366977, 34145223, 34180050, 34020708, 37094863, 36643085; Phenotypes: Neurodevelopmental disorder with variable motor and language impairment, MIM#617804; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 DDRGK1 Achchuthan Shanmugasundram reviewed gene: DDRGK1: Rating: GREEN; Mode of pathogenicity: ; Publications: 36243336, 35670300, 35377455, 28263186; Phenotypes: Spondyloepimetaphyseal dysplasia, Shohat type, MIM#602557; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 DCDC2 Achchuthan Shanmugasundram reviewed gene: DCDC2: Rating: AMBER; Mode of pathogenicity: ; Publications: 36816379, 35570614, 37296768, 34155636, 36938759; Phenotypes: Sclerosing cholangitis, neonatal, MIM#617394; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 DAW1 Achchuthan Shanmugasundram reviewed gene: DAW1: Rating: GREEN; Mode of pathogenicity: ; Publications: 36074124, 28991257; Phenotypes: Ciliary dyskinesia, primary, 52, MIM#620570; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 CYP2R1 Achchuthan Shanmugasundram reviewed gene: CYP2R1: Rating: RED; Mode of pathogenicity: ; Publications: 28548312, 15128933; Phenotypes: Rickets due to defect in vitamin D 25-hydroxylation deficiency, MIM#600081; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 CYP27B1 Achchuthan Shanmugasundram reviewed gene: CYP27B1: Rating: RED; Mode of pathogenicity: ; Publications: 27473561, 33823104, 9486994, 9415400, 34492747, 12050193; Phenotypes: Vitamin D-dependent rickets, type I, MIM#264700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 CYB5R3 Achchuthan Shanmugasundram reviewed gene: CYB5R3: Rating: AMBER; Mode of pathogenicity: ; Publications: 34467556; Phenotypes: Methemoglobinemia, type II, MIM#250800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 CUL3 Elizabeth Scotchman reviewed gene: CUL3: Rating: AMBER; Mode of pathogenicity: ; Publications: 31145527, 28135719, 31512373; Phenotypes: Neurodevelopmental disorder with or without autism or seizures, MIM#619239, Pseudohypoaldosteronism, type IIE, MIM#614496; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 CTSC Elizabeth Scotchman reviewed gene: CTSC: Rating: RED; Mode of pathogenicity: ; Publications: 14974080, 10662808, 32601924, 10581027, 11106356; Phenotypes: Papillon-Lefevre syndrome, MIM#245000, Haim-Munk syndrome, MIM#245010; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 CSTA Elizabeth Scotchman reviewed gene: CSTA: Rating: RED; Mode of pathogenicity: ; Publications: 25400170, 21944047, 12890214, 22066523; Phenotypes: Peeling skin syndrome 4, MIM#607936; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 CSMD1 Elizabeth Scotchman reviewed gene: CSMD1: Rating: AMBER; Mode of pathogenicity: ; Publications: 38816421; Phenotypes: Complex neurodevelopmental disorder, MONDO:0100038; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 CSGALNACT1 Elizabeth Scotchman reviewed gene: CSGALNACT1: Rating: GREEN; Mode of pathogenicity: ; Publications: 31325655, 31705726; Phenotypes: Skeletal dysplasia, mild, with joint laxity and advanced bone age, MIM#618870; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 CRELD1 Elizabeth Scotchman reviewed gene: CRELD1: Rating: AMBER; Mode of pathogenicity: ; Publications: 37947183; Phenotypes: Jeffries-Lakhani neurodevelopmental syndrome MIM#620771; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 COPB2 Elizabeth Scotchman reviewed gene: COPB2: Rating: AMBER; Mode of pathogenicity: ; Publications: 34450031, 29036432; Phenotypes: Microcephaly 19, primary, autosomal recessive, MIM#617800, Osteoporosis, childhood- or juvenile-onset, with developmental delay, MIM#619884; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v5.15 CNOT2 Elizabeth Scotchman reviewed gene: CNOT2: Rating: GREEN; Mode of pathogenicity: ; Publications: 31145527, 28135719, 31512373; Phenotypes: Intellectual developmental disorder with nasal speech, dysmorphic facies, and variable skeletal anomalies, MIM#618608; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 CLPP Elizabeth Scotchman reviewed gene: CLPP: Rating: AMBER; Mode of pathogenicity: ; Publications: 38249302, 37932750, 34338890, 38454547; Phenotypes: Perrault syndrome 3, MIM#614129; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 CLCN5 Elizabeth Scotchman reviewed gene: CLCN5: Rating: RED; Mode of pathogenicity: ; Publications: 36307859, 38267993, 37229200, 36495297; Phenotypes: Nephrolithiasis, type I, MIM#310468, Dent disease, MIM#300009, Hypophosphatemic rickets, MIM#300554; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v5.15 CHD8 Elizabeth Scotchman reviewed gene: CHD8: Rating: AMBER; Mode of pathogenicity: ; Publications: 31980904; Phenotypes: Intellectual developmental disorder with autism and macrocephaly, MIM#615032; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 CHD3 Elizabeth Scotchman reviewed gene: CHD3: Rating: AMBER; Mode of pathogenicity: ; Publications: 30397230, 32483341, 39050258, 37761804; Phenotypes: Snijders Blok-Campeau syndrome, MIM#618205; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 CEP295 Anna de Burca reviewed gene: CEP295: Rating: GREEN; Mode of pathogenicity: ; Publications: 38154379; Phenotypes: Seckel syndrome 11, MIM#620767; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 CELSR3 Anna de Burca reviewed gene: CELSR3: Rating: AMBER; Mode of pathogenicity: ; Publications: 38429302; Phenotypes: Neurodevelopmental disorder, MONDO#0700092, CELSR3-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 CDK10 Anna de Burca reviewed gene: CDK10: Rating: GREEN; Mode of pathogenicity: ; Publications: 28886341, 34974531; Phenotypes: Al Kaissi syndrome, MIM#617694; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 CDH2 Anna de Burca reviewed gene: CDH2: Rating: GREEN; Mode of pathogenicity: ; Publications: 31585109, 31650526; Phenotypes: Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, MIM#618929; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies v5.15 CD40LG Esther Kinning reviewed gene: CD40LG: Rating: AMBER; Mode of pathogenicity: ; Publications: 24631270, 6605368, 9255191, 8993019, 10228294, 35572607, 14451053; Phenotypes: Immunodeficiency, X-linked, with hyper-IgM, MIM#308230; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v5.15 CD151 Anna de Burca reviewed gene: CD151: Rating: RED; Mode of pathogenicity: ; Publications: 35519797, 20301543; Phenotypes: Epidermolysis bullosa simplex 7, with nephropathy and deafness, MIM#609057; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 CBY1 Anna de Burca reviewed gene: CBY1: Rating: GREEN; Mode of pathogenicity: ; Publications: 33131181, 25103236, 25220153; Phenotypes: cerebellar ataxia, molar tooth sign, Joubert syndrome, Intellectual disability, polydactyly; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 CASP2 Anna de Burca reviewed gene: CASP2: Rating: GREEN; Mode of pathogenicity: ; Publications: 37880421; Phenotypes: Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, MIM#620653; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 CAPRIN1 Anna de Burca reviewed gene: CAPRIN1: Rating: AMBER; Mode of pathogenicity: ; Publications: 35979925; Phenotypes: Neurodevelopmental disorder with language impairment, autism, and attention deficit-hyperactivity disorder, MIM#620782; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 CAMTA1 Anna de Burca reviewed gene: CAMTA1: Rating: AMBER; Mode of pathogenicity: ; Publications: 38044714; Phenotypes: Cerebellar dysfunction with variable cognitive and behavioral abnormalities, MIM#614756; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 CAMK2B Anna de Burca reviewed gene: CAMK2B: Rating: AMBER; Mode of pathogenicity: ; Publications: 37734707, 29560374, 29100089; Phenotypes: Intellectual developmental disorder, autosomal dominant 54, MIM#617799; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 CACNA1S Anna de Burca reviewed gene: CACNA1S: Rating: GREEN; Mode of pathogenicity: ; Publications: 38111203; Phenotypes: Congenital myopathy 18 due to dihydropyridine receptor defect, MIM#620246; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 CACHD1 Anna de Burca reviewed gene: CACHD1: Rating: AMBER; Mode of pathogenicity: ; Publications: 38158856; Phenotypes: Syndromic complex neurodevelopmental disorder, MONDO:0800439; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 C1GALT1C1 Anna de Burca reviewed gene: C1GALT1C1: Rating: AMBER; Mode of pathogenicity: ; Publications: 36599939, 37216524; Phenotypes: Hemolytic uremic syndrome, atypical, 8, with rhizomelic short stature, MIM#301110; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v5.15 C16orf62 Vicki Harrison reviewed gene: C16orf62: Rating: GREEN; Mode of pathogenicity: ; Publications: 36113987; Phenotypes: Ritscher-Schinzel syndrome 3, MIM#619135; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 BPTF Alice Gardham reviewed gene: BPTF: Rating: RED; Mode of pathogenicity: ; Publications: 36153657, 33522091; Phenotypes: Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies, MIM#617755; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 AXIN1 Alice Gardham reviewed gene: AXIN1: Rating: AMBER; Mode of pathogenicity: ; Publications: 37582359; Phenotypes: Craniometadiaphyseal osteosclerosis with hip dysplasia, MIM#620558; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 ATG7 Esther Kinning reviewed gene: ATG7: Rating: GREEN; Mode of pathogenicity: ; Publications: 34161705, 16625205, 17726112; Phenotypes: Spinocerebellar ataxia, autosomal recessive 31, MIM#619422; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 ASXL3 Alice Gardham reviewed gene: ASXL3: Rating: GREEN; Mode of pathogenicity: ; Publications: 38420660; Phenotypes: Bainbridge-Ropers syndrome, MIM#615485; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 ASPH Alice Gardham reviewed gene: ASPH: Rating: RED; Mode of pathogenicity: ; Publications: 11241487, 23687502, 30194805, 8749053, 24768550; Phenotypes: Traboulsi syndrome, MIM#601552; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 ASCC3 Alice Gardham reviewed gene: ASCC3: Rating: AMBER; Mode of pathogenicity: ; Publications: 21937992, 35047834; Phenotypes: Intellectual developmental disorder, autosomal recessive 81, MIM#620700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 ARV1 Alice Gardham reviewed gene: ARV1: Rating: AMBER; Mode of pathogenicity: ; Publications: 36307859, 34296759; Phenotypes: Developmental and epileptic encephalopathy 38, MIM#617020; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 AMOTL1 Alice Gardham reviewed gene: AMOTL1: 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: 36751037; Phenotypes: Orofacial clefting syndrome, MONDO:0015335, AMOTL1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 ALG5 Alice Gardham reviewed gene: ALG5: Rating: RED; Mode of pathogenicity: ; Publications: 35896117; Phenotypes: Polycystic kidney disease 7, MIM#620056; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v5.15 ALG13 Alice Gardham reviewed gene: ALG13: Rating: AMBER; Mode of pathogenicity: ; Publications: 32681751; Phenotypes: Developmental and epileptic encephalopathy 36, MIM#300884; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Fetal anomalies v5.15 ALG11 Alice Gardham reviewed gene: ALG11: Rating: AMBER; Mode of pathogenicity: ; Publications: 30770273; Phenotypes: Congenital disorder of glycosylation, type Ip, MIM#613661; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 AL117258.1 Elizabeth Scotchman reviewed gene: AL117258.1: Rating: GREEN; Mode of pathogenicity: ; Publications: 34903892, 39513328; Phenotypes: Heterotaxy, visceral, 12, autosomal, MIM#619702; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 ADD1 Alice Gardham reviewed gene: ADD1: Rating: GREEN; Mode of pathogenicity: ; Publications: 34906466; Phenotypes: Neurodevelopmental disorder, MONDO:0700092, ADD1-related; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v5.15 ADAMTS15 Alice Gardham reviewed gene: ADAMTS15: Rating: GREEN; Mode of pathogenicity: ; Publications: 35962790; Phenotypes: Arthrogryposis, distal, type 12, MIM#620545; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 ACBD6 Alice Gardham reviewed gene: ACBD6: Rating: GREEN; Mode of pathogenicity: ; Publications: 36457943, 34296759, 37951597; Phenotypes: Neurodevelopmental disorder with progressive movement abnormalities, MIM#620785; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.15 ABCD4 Alice Gardham reviewed gene: ABCD4: Rating: AMBER; Mode of pathogenicity: ; Publications: 33729671; Phenotypes: Methylmalonic aciduria and homocystinuria, cblJ type, MIM#614857; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.14 ROBO1 Achchuthan Shanmugasundram Phenotypes for gene: ROBO1 were changed from Neurooculorenal syndrome, OMIM:620305; Tetralogy of Fallot and septal defects to Neurooculorenal syndrome, OMIM:620305
Fetal anomalies v5.13 ZSCAN10 Achchuthan Shanmugasundram gene: ZSCAN10 was added
gene: ZSCAN10 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: ZSCAN10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZSCAN10 were set to 38386308
Phenotypes for gene: ZSCAN10 were set to Otofacial neurodevelopmental syndrome, OMIM:620910
Fetal anomalies v5.13 ZRSR2 Achchuthan Shanmugasundram gene: ZRSR2 was added
gene: ZRSR2 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: ZRSR2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZRSR2 were set to 38158857
Phenotypes for gene: ZRSR2 were set to Orofaciodigital syndrome XXI, OMIM:301132
Fetal anomalies v5.13 ZNF750 Achchuthan Shanmugasundram Source NHS GMS was added to ZNF750.
Source Expert Review Red was added to ZNF750.
Added phenotypes Seborrhea-like dermatitis with psoriasiform elements, OMIM:610227 for gene: ZNF750
Publications for gene: ZNF750 were updated from to 16751772
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Fetal anomalies v5.13 ZNF687 Achchuthan Shanmugasundram gene: ZNF687 was added
gene: ZNF687 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: ZNF687 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNF687 were set to 26849110; 29493781
Phenotypes for gene: ZNF687 were set to Paget disease of bone 6, OMIM:616833
Fetal anomalies v5.13 ZNF423 Achchuthan Shanmugasundram Source NHS GMS was added to ZNF423.
Publications for gene: ZNF423 were updated from 22863007 to 39071699; 33531950; 22863007; 32925911
Fetal anomalies v5.13 ZMYND8 Achchuthan Shanmugasundram gene: ZMYND8 was added
gene: ZMYND8 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: ZMYND8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZMYND8 were set to 35916866; 32530565
Phenotypes for gene: ZMYND8 were set to Neurodevelopmental disorder, MONDO:0700092, ZMYND8-related
Fetal anomalies v5.13 ZFX Achchuthan Shanmugasundram gene: ZFX was added
gene: ZFX was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: ZFX was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: ZFX were set to 38325380
Phenotypes for gene: ZFX were set to Intellectual developmental disorder, X-linked syndromic 37, OMIM:301118
Fetal anomalies v5.13 XPNPEP3 Achchuthan Shanmugasundram gene: XPNPEP3 was added
gene: XPNPEP3 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: XPNPEP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: XPNPEP3 were set to 32660933; 20179356
Phenotypes for gene: XPNPEP3 were set to Nephronophthisis-like nephropathy 1 OMIM:613159
Fetal anomalies v5.13 WNT9B Achchuthan Shanmugasundram Source NHS GMS was added to WNT9B.
Fetal anomalies v5.13 WISP3 Achchuthan Shanmugasundram gene: WISP3 was added
gene: WISP3 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: WISP3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WISP3 were set to Progressive pseudorheumatoid dysplasia, OMIM:208230
Fetal anomalies v5.13 WDR44 Achchuthan Shanmugasundram gene: WDR44 was added
gene: WDR44 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: WDR44 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: WDR44 were set to 38191484
Phenotypes for gene: WDR44 were set to Ciliopathy, MONDO:0005308, WDR44-related
Fetal anomalies v5.13 WBP4 Achchuthan Shanmugasundram gene: WBP4 was added
gene: WBP4 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: WBP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WBP4 were set to 37963460; 37425688
Phenotypes for gene: WBP4 were set to Neurodevelopemental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalities, OMIM:620852
Fetal anomalies v5.13 WASHC5 Achchuthan Shanmugasundram Source NHS GMS was added to WASHC5.
Source Expert Review Amber was added to WASHC5.
Added phenotypes Ritscher-Schinzel syndrome 1, OMIM:220210 for gene: WASHC5
Publications for gene: WASHC5 were updated from to 24065355
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Fetal anomalies v5.13 VHL Achchuthan Shanmugasundram gene: VHL was added
gene: VHL was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: VHL was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: VHL were set to von Hippel-Lindau syndrome, OMIM:193300
Fetal anomalies v5.13 UQCC2 Achchuthan Shanmugasundram Source NHS GMS was added to UQCC2.
Fetal anomalies v5.13 UNC45A Achchuthan Shanmugasundram gene: UNC45A was added
gene: UNC45A was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: UNC45A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UNC45A were set to 29429573
Phenotypes for gene: UNC45A were set to Osteootohepatoenteric syndrome, OMIM:619377
Fetal anomalies v5.13 UFSP2 Achchuthan Shanmugasundram gene: UFSP2 was added
gene: UFSP2 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: UFSP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: UFSP2 were set to 28892125; 32755715; 33473208; 26428751
Phenotypes for gene: UFSP2 were set to Spondyloepimetaphyseal dysplasia, Di Rocco type, OMIM:617974; ?Hip dysplasia, Beukes type, OMIM:142669
Fetal anomalies v5.13 U2AF2 Achchuthan Shanmugasundram gene: U2AF2 was added
gene: U2AF2 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: U2AF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: U2AF2 were set to 34112922; 37134193; 37092751; 36747105
Phenotypes for gene: U2AF2 were set to Developmental delay, dysmorphic facies, and brain anomalies OMIM:620535
Fetal anomalies v5.13 TYROBP Achchuthan Shanmugasundram gene: TYROBP was added
gene: TYROBP was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: TYROBP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TYROBP were set to Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1, OMIM:221770
Fetal anomalies v5.13 TULP3 Achchuthan Shanmugasundram gene: TULP3 was added
gene: TULP3 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: TULP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TULP3 were set to 30799240; 36276950; 36460032; 35397207; 30799239
Phenotypes for gene: TULP3 were set to Hepatorenocardiac degenerative fibrosis, OMIM:619902
Fetal anomalies v5.13 TUFM Achchuthan Shanmugasundram Source NHS GMS was added to TUFM.
Added phenotypes Combined oxidative phosphorylation deficiency 4, OMIM:610678 for gene: TUFM
Publications for gene: TUFM were updated from to 26741492; 17160893
Fetal anomalies v5.13 TTC25 Achchuthan Shanmugasundram Source NHS GMS was added to TTC25.
Added phenotypes Ciliary dyskinesia, primary, 35, OMIM:617092 for gene: TTC25
Publications for gene: TTC25 were updated from to 33746037; 34215651; 33715250; 31765523; 27486780
Fetal anomalies v5.13 TSHZ3 Achchuthan Shanmugasundram gene: TSHZ3 was added
gene: TSHZ3 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: TSHZ3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TSHZ3 were set to 36553458; 34919690; 39420202
Phenotypes for gene: TSHZ3 were set to Congenital anomaly of kidney and urinary tract
Fetal anomalies v5.13 TRPM7 Achchuthan Shanmugasundram Source NHS GMS was added to TRPM7.
Source Expert Review Red was added to TRPM7.
Added phenotypes Amyotrophic lateral sclerosis-parkinsonism/dementia complex, susceptibility to, OMIM:105500 for gene: TRPM7
Publications for gene: TRPM7 were updated from 32503408; 31423533 to 39099563; 39621058; 35712613; 35561741; 31423533; 32503408
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Fetal anomalies v5.13 TRIT1 Achchuthan Shanmugasundram Source NHS GMS was added to TRIT1.
Publications for gene: TRIT1 were updated from 32088416 to 36049610; 32088416
Fetal anomalies v5.13 TREM2 Achchuthan Shanmugasundram gene: TREM2 was added
gene: TREM2 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: TREM2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TREM2 were set to Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2, OMIM:618193
Fetal anomalies v5.13 TONSL Achchuthan Shanmugasundram gene: TONSL was added
gene: TONSL was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: TONSL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TONSL were set to 32959051; 30773278; 30773277
Phenotypes for gene: TONSL were set to Spondyloepimetaphyseal dysplasia, sponastrime type OMIM:271510
Fetal anomalies v5.13 TOMM7 Achchuthan Shanmugasundram gene: TOMM7 was added
gene: TOMM7 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: TOMM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOMM7 were set to 36282599; 36299998
Phenotypes for gene: TOMM7 were set to Garg-Mishra progeroid syndrome, OMIM:620601
Fetal anomalies v5.13 TOGARAM1 Achchuthan Shanmugasundram Source NHS GMS was added to TOGARAM1.
Source Expert Review Amber was added to TOGARAM1.
Added phenotypes Joubert syndrome 37, OMIM:619185 for gene: TOGARAM1
Publications for gene: TOGARAM1 were updated from 32747439 to 32453716; 32747439
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Fetal anomalies v5.13 TNRC6B Achchuthan Shanmugasundram gene: TNRC6B was added
gene: TNRC6B was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: TNRC6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TNRC6B were set to 29463886; 32152250
Phenotypes for gene: TNRC6B were set to Global developmental delay with speech and behavioral abnormalities, OMIM:61924
Fetal anomalies v5.13 TNFSF11 Achchuthan Shanmugasundram gene: TNFSF11 was added
gene: TNFSF11 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: TNFSF11 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TNFSF11 were set to Osteopetrosis, autosomal recessive 2, OMIM:259710
Fetal anomalies v5.13 TNFRSF13B Achchuthan Shanmugasundram Source NHS GMS was added to TNFRSF13B.
Source Expert Review Red was added to TNFRSF13B.
Mode of inheritance for gene TNFRSF13B was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Added phenotypes Immunodeficiency, common variable, 2, OMIM:240500 for gene: TNFRSF13B
Publications for gene: TNFRSF13B were updated from to 16007087; 16007086
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Fetal anomalies v5.13 THSD1 Achchuthan Shanmugasundram Source NHS GMS was added to THSD1.
Added phenotypes Lymphatic malformation 13, OMIM:620244 for gene: THSD1
Publications for gene: THSD1 were updated from 26036949; 28749478 to 26036949; 30055085; 33569873; 27895300; 28749478; 37993095
Fetal anomalies v5.13 TBR1 Achchuthan Shanmugasundram Source NHS GMS was added to TBR1.
Mode of inheritance for gene TBR1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Intellectual developmental disorder with autism and speech delay, OMIM:606053 for gene: TBR1
Publications for gene: TBR1 were updated from to 32005960
Fetal anomalies v5.13 TAF8 Achchuthan Shanmugasundram gene: TAF8 was added
gene: TAF8 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: TAF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAF8 were set to 39169228
Phenotypes for gene: TAF8 were set to Neurodevelopmental disorder with severe motor impairment, absent language, cerebral hypomyelination, and brain atrophy, OMIM:619972
Fetal anomalies v5.13 TACR3 Achchuthan Shanmugasundram Source NHS GMS was added to TACR3.
Source Expert Review Red was added to TACR3.
Added phenotypes Hypogonadotropic hypogonadism 11 with or without anosmia, OMIM:614840 for gene: TACR3
Publications for gene: TACR3 were updated from to 20332248; 19079066
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Fetal anomalies v5.13 TAC3 Achchuthan Shanmugasundram Source NHS GMS was added to TAC3.
Source Expert Review Red was added to TAC3.
Added phenotypes Hypogonadotropic hypogonadism 10 with or without anosmia, OMIM:614839 for gene: TAC3
Publications for gene: TAC3 were updated from to 20332248
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Fetal anomalies v5.13 STX5 Achchuthan Shanmugasundram gene: STX5 was added
gene: STX5 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: STX5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STX5 were set to 34711829
Phenotypes for gene: STX5 were set to ?Congenital disorder of glycosylation, type IIaa, OMIM:620454
Fetal anomalies v5.13 STAG1 Achchuthan Shanmugasundram Source NHS GMS was added to STAG1.
Mode of inheritance for gene STAG1 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
Added phenotypes Intellectual developmental disorder, autosomal dominant 47, OMIM:617635 for gene: STAG1
Publications for gene: STAG1 were updated from to 28119487; 39224759; 34440290
Fetal anomalies v5.13 SPIN4 Achchuthan Shanmugasundram gene: SPIN4 was added
gene: SPIN4 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: SPIN4 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: SPIN4 were set to 36927955
Phenotypes for gene: SPIN4 were set to ?Lui-Jee-Baron syndrome, OMIM:301114
Fetal anomalies v5.13 SNUPN Achchuthan Shanmugasundram gene: SNUPN was added
gene: SNUPN was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: SNUPN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNUPN were set to 38413582; 38366623
Phenotypes for gene: SNUPN were set to Muscular dystrophy, limb-girdle, autosomal recessive 29, OMIM:620793
Fetal anomalies v5.13 SNRPE Achchuthan Shanmugasundram Source NHS GMS was added to SNRPE.
Source Expert Review Red was added to SNRPE.
Mode of inheritance for gene SNRPE was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Hypotrichosis 11, OMIM:615059 for gene: SNRPE
Publications for gene: SNRPE were updated from to 9621144; 33792916
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Fetal anomalies v5.13 SNF8 Achchuthan Shanmugasundram gene: SNF8 was added
gene: SNF8 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: SNF8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SNF8 were set to 38423010
Phenotypes for gene: SNF8 were set to Neurodevelopmental disorder plus optic atrophy, OMIM:620784; Developmental and epileptic encephalopathy 115, OMIM:620783
Fetal anomalies v5.13 SNAP25 Achchuthan Shanmugasundram Source NHS GMS was added to SNAP25.
Mode of inheritance for gene SNAP25 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Myasthenic syndrome, congenital, 18, OMIM:616330 for gene: SNAP25
Publications for gene: SNAP25 were updated from to 33299146; 36379720
Fetal anomalies v5.13 SMPD1 Achchuthan Shanmugasundram Source NHS GMS was added to SMPD1.
Added phenotypes Niemann-Pick disease, type B, OMIM:607616; Niemann-Pick disease, type A, OMIM:257200 for gene: SMPD1
Fetal anomalies v5.13 SMOC2 Achchuthan Shanmugasundram Source NHS GMS was added to SMOC2.
Source Expert Review Red was added to SMOC2.
Added phenotypes Dentin dysplasia, type I, with microdontia and misshapen teeth, OMIM:125400 for gene: SMOC2
Publications for gene: SMOC2 were updated from to 22152679; 23317772
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Fetal anomalies v5.13 SLCO2A1 Achchuthan Shanmugasundram gene: SLCO2A1 was added
gene: SLCO2A1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: SLCO2A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: SLCO2A1 were set to Hypertrophic osteoarthropathy, primary, autosomal dominant, OMIM:167100; PHOAR2-enteropathy syndrome, OMIM:614441
Fetal anomalies v5.13 SLC4A10 Achchuthan Shanmugasundram gene: SLC4A10 was added
gene: SLC4A10 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: SLC4A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC4A10 were set to 38054405; 37459438; 31130284
Phenotypes for gene: SLC4A10 were set to Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, OMIM:620746
Fetal anomalies v5.13 SLC35A1 Achchuthan Shanmugasundram Source NHS GMS was added to SLC35A1.
Added phenotypes Congenital disorder of glycosylation, type IIf, OMIM:603585 for gene: SLC35A1
Publications for gene: SLC35A1 were updated from to 28856833; 30115659
Fetal anomalies v5.13 SLC34A3 Achchuthan Shanmugasundram gene: SLC34A3 was added
gene: SLC34A3 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: SLC34A3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC34A3 were set to Hypophosphatemic rickets with hypercalciuria, OMIM:241530
Fetal anomalies v5.13 SLC34A1 Achchuthan Shanmugasundram gene: SLC34A1 was added
gene: SLC34A1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: SLC34A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC34A1 were set to 9560283; 12324554; 25050900
Phenotypes for gene: SLC34A1 were set to Infantile hypercalcemia-2, OMIM:616963
Fetal anomalies v5.13 SLC30A7 Achchuthan Shanmugasundram gene: SLC30A7 was added
gene: SLC30A7 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: SLC30A7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC30A7 were set to 36821639
Phenotypes for gene: SLC30A7 were set to Ziegler-Huang syndrome, OMIM:620501
Fetal anomalies v5.13 SLC25A4 Achchuthan Shanmugasundram Source NHS GMS was added to SLC25A4.
Mode of inheritance for gene SLC25A4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD, OMIM:617184 for gene: SLC25A4
Publications for gene: SLC25A4 were updated from to 27693233; 30013777
Fetal anomalies v5.13 SLC24A4 Achchuthan Shanmugasundram Source NHS GMS was added to SLC24A4.
Source Expert Review Red was added to SLC24A4.
Added phenotypes Amelogenesis imperfecta, type IIA5, OMIM:615887 for gene: SLC24A4
Publications for gene: SLC24A4 were updated from to 23375655; 24621671
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Fetal anomalies v5.13 SIAH1 Achchuthan Shanmugasundram gene: SIAH1 was added
gene: SIAH1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: SIAH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SIAH1 were set to 32430360
Phenotypes for gene: SIAH1 were set to Buratti-Harel syndrome, OMIM:619314
Fetal anomalies v5.13 SHROOM4 Achchuthan Shanmugasundram Source NHS GMS was added to SHROOM4.
Added phenotypes Abnormal corpus callosum for gene: SHROOM4
Publications for gene: SHROOM4 were updated from 32565546 to 36379543; 32565546
Fetal anomalies v5.13 SHROOM3 Achchuthan Shanmugasundram Source NHS GMS was added to SHROOM3.
Publications for gene: SHROOM3 were updated from to 32621286
Fetal anomalies v5.13 SH3BP2 Achchuthan Shanmugasundram gene: SH3BP2 was added
gene: SH3BP2 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: SH3BP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SH3BP2 were set to Cherubism, OMIM:118400
Fetal anomalies v5.13 SGMS2 Achchuthan Shanmugasundram gene: SGMS2 was added
gene: SGMS2 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: SGMS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SGMS2 were set to 32028018; 30779713
Phenotypes for gene: SGMS2 were set to Calvarial doughnut lesions with bone fragility with or without spondylometaphyseal dysplasia, OMIM:126550
Fetal anomalies v5.13 SFRP4 Achchuthan Shanmugasundram gene: SFRP4 was added
gene: SFRP4 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: SFRP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SFRP4 were set to 20174869; 27117872; 28100910; 22387305; 26273529; 27355534; 22965941; 24096177
Phenotypes for gene: SFRP4 were set to Pyle disease, OMIM:265900
Fetal anomalies v5.13 SETD1A Achchuthan Shanmugasundram Source NHS GMS was added to SETD1A.
Added phenotypes Neurodevelopmental disorder with speech impairment and dysmorphic facies, OMIM:619056 for gene: SETD1A
Publications for gene: SETD1A were updated from to 37000069
Fetal anomalies v5.13 SCYL2 Achchuthan Shanmugasundram gene: SCYL2 was added
gene: SCYL2 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: SCYL2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SCYL2 were set to 39138116; 39169672
Phenotypes for gene: SCYL2 were set to Arthrogryposis multiplex congenita 4, neurogenic, with agenesis of the corpus callosum, OMIM:618766
Fetal anomalies v5.13 SASS6 Achchuthan Shanmugasundram Source NHS GMS was added to SASS6.
Added phenotypes Microcephaly 14, primary, autosomal recessive, OMIM:616402 for gene: SASS6
Publications for gene: SASS6 were updated from 24951542 to 38501757; 24951542; 30639237; 36739862
Fetal anomalies v5.13 RSPRY1 Achchuthan Shanmugasundram Source NHS GMS was added to RSPRY1.
Added phenotypes Spondyloepimetaphyseal dysplasia, Faden-Alkuraya type, OMIM:616723 for gene: RSPRY1
Publications for gene: RSPRY1 were updated from to 26365341; 38562122; 30063090
Fetal anomalies v5.13 RSPO2 Achchuthan Shanmugasundram gene: RSPO2 was added
gene: RSPO2 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: RSPO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RSPO2 were set to 29769720; 32457899
Phenotypes for gene: RSPO2 were set to Tetraamelia syndrome 2, OMIM:618021
Fetal anomalies v5.13 RRAS Achchuthan Shanmugasundram Source NHS GMS was added to RRAS.
Mode of pathogenicity for gene RRAS was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Added phenotypes Noonan syndrome, MONDO:0018997 for gene: RRAS
Publications for gene: RRAS were updated from 24705357; 32815881; 34935735 to 34935735; 32815881; 24705357
Fetal anomalies v5.13 RRAGC Achchuthan Shanmugasundram gene: RRAGC was added
gene: RRAGC was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: RRAGC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RRAGC were set to 27234373; 37057673
Phenotypes for gene: RRAGC were set to Long-Olsen syndrome, OMIM:620609
Fetal anomalies v5.13 RPL13 Achchuthan Shanmugasundram gene: RPL13 was added
gene: RPL13 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: RPL13 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RPL13 were set to 31630789
Phenotypes for gene: RPL13 were set to Spondyloepimetaphyseal dysplasia, Isidor-Toutain type, OMIM:618728
Fetal anomalies v5.13 ROBO2 Achchuthan Shanmugasundram gene: ROBO2 was added
gene: ROBO2 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: ROBO2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ROBO2 were set to 19350278; 17357069; 26026792; 29194579; 34059960; 18235093; 24429398
Phenotypes for gene: ROBO2 were set to Vesicoureteral reflux 2, OMIM:610878
Fetal anomalies v5.13 ROBO1 Achchuthan Shanmugasundram Source NHS GMS was added to ROBO1.
Added phenotypes Neurooculorenal syndrome, OMIM:620305 for gene: ROBO1
Publications for gene: ROBO1 were updated from 28592524; 28485101; 30712880; 29194579; 35227688 to 35227688; 28592524; 28286008; 28485101; 30712880; 29194579
Fetal anomalies v5.13 RNU4-2 Achchuthan Shanmugasundram gene: RNU4-2 was added
gene: RNU4-2 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: RNU4-2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RNU4-2 were set to 38821540; 38859706; 38991538
Phenotypes for gene: RNU4-2 were set to ReNU syndrome, OMIM:620851
Fetal anomalies v5.13 RINT1 Achchuthan Shanmugasundram gene: RINT1 was added
gene: RINT1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: RINT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RINT1 were set to 31204009
Phenotypes for gene: RINT1 were set to Infantile liver failure syndrome 3 OMIM:618641
Fetal anomalies v5.13 RFWD3 Achchuthan Shanmugasundram Source NHS GMS was added to RFWD3.
Source Expert Review Amber was added to RFWD3.
Publications for gene: RFWD3 were updated from 28691929 to 2869192; 38058754; 28691929
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Fetal anomalies v5.13 RASGRP2 Achchuthan Shanmugasundram gene: RASGRP2 was added
gene: RASGRP2 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: RASGRP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RASGRP2 were set to 24958846; 18709451
Phenotypes for gene: RASGRP2 were set to ?Bleeding disorder, platelet-type, 18, OMIM:615888
Fetal anomalies v5.13 RAP1B Achchuthan Shanmugasundram Source Expert Review Amber was added to RAP1B.
Mode of pathogenicity for gene RAP1B was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Publications for gene: RAP1B were updated from 26280580; 32627184 to 35451551; 37850357; 26280580; 32627184
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Fetal anomalies v5.13 RAB34 Achchuthan Shanmugasundram gene: RAB34 was added
gene: RAB34 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: RAB34 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB34 were set to 37619988; 37384395
Phenotypes for gene: RAB34 were set to Orofaciodigital syndrome XX, OMIM:620718
Fetal anomalies v5.13 PUM1 Achchuthan Shanmugasundram gene: PUM1 was added
gene: PUM1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: PUM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PUM1 were set to 30903679; 29474920; 25768905; 35386260; 31859446
Phenotypes for gene: PUM1 were set to Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, OMIM:620719
Fetal anomalies v5.13 PSMF1 Achchuthan Shanmugasundram gene: PSMF1 was added
gene: PSMF1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: PSMF1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PSMF1 were set to 39148840
Phenotypes for gene: PSMF1 were set to Complex neurodevelopmental disorder with motor features, MONDO:0100516, PSMF1-related
Fetal anomalies v5.13 PSMC3 Achchuthan Shanmugasundram gene: PSMC3 was added
gene: PSMC3 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: PSMC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMC3 were set to 37256937
Phenotypes for gene: PSMC3 were set to neurodevelopmental disorder, MONDO:0700092
Fetal anomalies v5.13 PSMB9 Achchuthan Shanmugasundram gene: PSMB9 was added
gene: PSMB9 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: PSMB9 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMB9 were set to 33727065; 34819510
Phenotypes for gene: PSMB9 were set to Proteasome-associated autoinflammatory syndrome 6, OMIM:620796
Fetal anomalies v5.13 PRKG2 Achchuthan Shanmugasundram gene: PRKG2 was added
gene: PRKG2 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: PRKG2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRKG2 were set to 33106379; 34680883; 34782440
Phenotypes for gene: PRKG2 were set to Acromesomelic dysplasia 4, OMIM:619636; Spondylometaphyseal dysplasia, Pagnamenta type, OMIM:619638
Fetal anomalies v5.13 PRKCSH Achchuthan Shanmugasundram gene: PRKCSH was added
gene: PRKCSH was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: PRKCSH was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PRKCSH were set to 12577059; 24886261; 12529853
Phenotypes for gene: PRKCSH were set to Polycystic liver disease 1 with or without kidney cysts, OMIM:174050
Fetal anomalies v5.13 PLS3 Achchuthan Shanmugasundram gene: PLS3 was added
gene: PLS3 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: PLS3 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: PLS3 were set to 32655496; 28777485; 29736964; 37751738; 25209159; 29884797; 24088043
Phenotypes for gene: PLS3 were set to Diaphragmatic hernia 5, X-linked, OMIM:306950
Mode of pathogenicity for gene: PLS3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Fetal anomalies v5.13 PLD1 Achchuthan Shanmugasundram Publications for gene: PLD1 were updated from 27799408; 33645542; 33142350 to 33645542; 27799408; 33142350
Fetal anomalies v5.13 PKDCC Achchuthan Shanmugasundram gene: PKDCC was added
gene: PKDCC was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: PKDCC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PKDCC were set to 19097194; 30478137
Phenotypes for gene: PKDCC were set to Rhizomelic limb shortening with dysmorphic features, OMIM:618821
Fetal anomalies v5.13 PISD Achchuthan Shanmugasundram gene: PISD was added
gene: PISD was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: PISD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PISD were set to 30488656; 3561949; 30858161; 31263216
Phenotypes for gene: PISD were set to Liberfarb syndrome, OMIM:618889
Fetal anomalies v5.13 PIP5K1C Achchuthan Shanmugasundram gene: PIP5K1C was added
gene: PIP5K1C was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: PIP5K1C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIP5K1C were set to 38491417; 17701898
Phenotypes for gene: PIP5K1C were set to Lethal congenital contractural syndrome 3, OMIM:611369
Fetal anomalies v5.13 PIGY Achchuthan Shanmugasundram Source NHS GMS was added to PIGY.
Added phenotypes Hyperphosphatasia with impaired intellectual development syndrome 6, OMIM:616809 for gene: PIGY
Publications for gene: PIGY were updated from to 26293662; 38790248
Fetal anomalies v5.13 PIGS Achchuthan Shanmugasundram Source NHS GMS was added to PIGS.
Publications for gene: PIGS were updated from 30269814 to 30269814; 37035392; 33410539
Fetal anomalies v5.13 PIGG Achchuthan Shanmugasundram Source NHS GMS was added to PIGG.
Added phenotypes Neurodevelopmental disorder with or without hypotonia, seizures, and cerebellar atrophy, OMIM:616917 for gene: PIGG
Publications for gene: PIGG were updated from to 26996948; 34113002
Fetal anomalies v5.13 PI4K2A Achchuthan Shanmugasundram gene: PI4K2A was added
gene: PI4K2A was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: PI4K2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PI4K2A were set to 35880319; 32418222; 30564627
Phenotypes for gene: PI4K2A were set to Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities, OMIM:620732
Fetal anomalies v5.13 PHLDB1 Achchuthan Shanmugasundram gene: PHLDB1 was added
gene: PHLDB1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: PHLDB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PHLDB1 were set to 36543534
Phenotypes for gene: PHLDB1 were set to Osteogenesis imperfecta, type XXIII, OMIM:620639
Fetal anomalies v5.13 PAN2 Achchuthan Shanmugasundram gene: PAN2 was added
gene: PAN2 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: PAN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PAN2 were set to 35304602; 29620724
Phenotypes for gene: PAN2 were set to syndromic disease MONDO:0002254
Fetal anomalies v5.13 NUP214 Achchuthan Shanmugasundram gene: NUP214 was added
gene: NUP214 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: NUP214 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP214 were set to 31178128; 38179855; 30758658; 3965093
Phenotypes for gene: NUP214 were set to Encephalopathy, acute, infection-induced, susceptibility to, 9, OMIM:618426
Fetal anomalies v5.13 NUDT2 Achchuthan Shanmugasundram gene: NUDT2 was added
gene: NUDT2 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: NUDT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUDT2 were set to 38141063
Phenotypes for gene: NUDT2 were set to Intellectual developmental disorder with or without peripheral neuropathy, OMIM:619844
Fetal anomalies v5.13 NUAK2 Achchuthan Shanmugasundram Source NHS GMS was added to NUAK2.
Source Expert Review Red was added to NUAK2.
Added phenotypes ?Anencephaly 2, OMIM:619452 for gene: NUAK2
Publications for gene: NUAK2 were updated from 32845958; 22689267 to 22689267; 32845958
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Fetal anomalies v5.13 NSUN6 Achchuthan Shanmugasundram gene: NSUN6 was added
gene: NSUN6 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: NSUN6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NSUN6 were set to 37226891
Phenotypes for gene: NSUN6 were set to Intellectual developmental disorder, autosomal recessive 82, OMIM:620779
Fetal anomalies v5.13 NSUN2 Achchuthan Shanmugasundram Source NHS GMS was added to NSUN2.
Source Expert Review Red was added to NSUN2.
Added phenotypes Intellectual developmental disorder, autosomal recessive 5, OMIM:611091 for gene: NSUN2
Publications for gene: NSUN2 were updated from to 37305761; 36420349; 38643142; 33002343
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Fetal anomalies v5.13 NPR3 Achchuthan Shanmugasundram gene: NPR3 was added
gene: NPR3 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: NPR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPR3 were set to 30032985; 10468599
Phenotypes for gene: NPR3 were set to Boudin-Mortier syndrome, OMIM:619543
Fetal anomalies v5.13 NPNT Achchuthan Shanmugasundram gene: NPNT was added
gene: NPNT was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: NPNT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NPNT were set to 34049960; 35246978; 17537792
Phenotypes for gene: NPNT were set to Renal agenesis, MONDO:0018470, NPNT-related
Fetal anomalies v5.13 NLRP3 Achchuthan Shanmugasundram Source Expert Review Amber was added to NLRP3.
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Fetal anomalies v5.13 NHP2 Achchuthan Shanmugasundram Source NHS GMS was added to NHP2.
Added phenotypes Dyskeratosis congenita, autosomal recessive 2, OMIM:613987 for gene: NHP2
Publications for gene: NHP2 were updated from to 18523010
Fetal anomalies v5.13 NARS Achchuthan Shanmugasundram gene: NARS was added
gene: NARS was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: NARS was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: NARS were set to 32738225; 32788587
Phenotypes for gene: NARS were set to Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, autosomal recessive, OMIM:619091; Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, autosomal dominant, OMIM:619092
Fetal anomalies v5.13 MSTO1 Achchuthan Shanmugasundram Source NHS GMS was added to MSTO1.
Publications for gene: MSTO1 were updated from 29339779; 28544275; 31604776; 31130378; 28554942; 37431817 to 31463572; 37431817; 28554942; 29339779; 28544275; 30684668; 31130378; 31604776
Fetal anomalies v5.13 MMP2 Achchuthan Shanmugasundram gene: MMP2 was added
gene: MMP2 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: MMP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMP2 were set to 16542393
Phenotypes for gene: MMP2 were set to Multicentric osteolysis, nodulosis, and arthropathy, OMIM:259600
Fetal anomalies v5.13 MMP15 Achchuthan Shanmugasundram Source NHS GMS was added to MMP15.
Publications for gene: MMP15 were updated from 33875846 to 33875846; 34988996
Fetal anomalies v5.13 MIR17HG Achchuthan Shanmugasundram Source NHS GMS was added to MIR17HG.
Publications for gene: MIR17HG were updated from to 36588757; 30672094; 26360630; 33818875
Fetal anomalies v5.13 MDFIC Achchuthan Shanmugasundram Source NHS GMS was added to MDFIC.
Fetal anomalies v5.13 MBOAT7 Achchuthan Shanmugasundram Source NHS GMS was added to MBOAT7.
Added phenotypes Intellectual developmental disorder, autosomal recessive 57, OMIM:617188 for gene: MBOAT7
Publications for gene: MBOAT7 were updated from to 36672789; 38088234; 32645526; 33335874; 38407511; 32744787; 34979703; 31852446; 37628684
Fetal anomalies v5.13 MAX Achchuthan Shanmugasundram gene: MAX was added
gene: MAX was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: MAX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAX were set to 38141607
Phenotypes for gene: MAX were set to Polydactyly-macrocephaly syndrome, OMIM:620712
Fetal anomalies v5.13 MAPKBP1 Achchuthan Shanmugasundram gene: MAPKBP1 was added
gene: MAPKBP1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: MAPKBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAPKBP1 were set to 28089251
Phenotypes for gene: MAPKBP1 were set to Nephronophthisis 20, OMIM:617271
Fetal anomalies v5.13 MAP4K4 Achchuthan Shanmugasundram gene: MAP4K4 was added
gene: MAP4K4 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: MAP4K4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP4K4 were set to 37126546
Phenotypes for gene: MAP4K4 were set to RASopathy, MONDO:0021060, MAP4K4-related
Fetal anomalies v5.13 LSM11 Achchuthan Shanmugasundram gene: LSM11 was added
gene: LSM11 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: LSM11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LSM11 were set to 33230297
Phenotypes for gene: LSM11 were set to ?Aicardi-Goutieres syndrome 8, OMIM:619486
Fetal anomalies v5.13 LRRK1 Achchuthan Shanmugasundram gene: LRRK1 was added
gene: LRRK1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: LRRK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRK1 were set to 32119750; 27829680; 27055475; 31571209
Phenotypes for gene: LRRK1 were set to Osteosclerotic metaphyseal dysplasia, OMIM:615198
Fetal anomalies v5.13 LRIG2 Achchuthan Shanmugasundram Source NHS GMS was added to LRIG2.
Publications for gene: LRIG2 were updated from to 30885509; 27855655; 23313374
Fetal anomalies v5.13 LRBA Achchuthan Shanmugasundram Source NHS GMS was added to LRBA.
Source Expert Review Red was added to LRBA.
Added phenotypes Immunodeficiency, common variable, 8, with autoimmunity, OMIM:614700 for gene: LRBA
Publications for gene: LRBA were updated from to 22721650; 22981790; 25468195; 26206937; 22608502
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Fetal anomalies v5.13 LRAT Achchuthan Shanmugasundram Source NHS GMS was added to LRAT.
Source Expert Review Red was added to LRAT.
Added phenotypes Leber congenital amaurosis 14, OMIM:613341 for gene: LRAT
Publications for gene: LRAT were updated from to 18055821; 17011878; 11381255
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Fetal anomalies v5.13 LPIN2 Achchuthan Shanmugasundram gene: LPIN2 was added
gene: LPIN2 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: LPIN2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LPIN2 were set to 29912021
Phenotypes for gene: LPIN2 were set to Majeed syndrome, OMIM:609628
Fetal anomalies v5.13 LOX Achchuthan Shanmugasundram Source NHS GMS was added to LOX.
Added phenotypes Aortic aneurysm, familial thoracic 10, OMIM:617168 for gene: LOX
Publications for gene: LOX were updated from 31742715 to 31742715; 33866545
Fetal anomalies v5.13 LNPK Achchuthan Shanmugasundram gene: LNPK was added
gene: LNPK was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: LNPK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LNPK were set to 30032983; 35599435; 37794925
Phenotypes for gene: LNPK were set to Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum, OMIM:618090
Fetal anomalies v5.13 LIPT2 Achchuthan Shanmugasundram Source NHS GMS was added to LIPT2.
Added phenotypes Encephalopathy, neonatal severe, with lactic acidosis and brain abnormalities, OMIM:617668 for gene: LIPT2
Publications for gene: LIPT2 were updated from to 28757203; 39536593
Fetal anomalies v5.13 LIPN Achchuthan Shanmugasundram Source NHS GMS was added to LIPN.
Source Expert Review Red was added to LIPN.
Added phenotypes Ichthyosis, congenital, autosomal recessive 8, OMIM:613943 for gene: LIPN
Publications for gene: LIPN were updated from to 21439540
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Fetal anomalies v5.13 LINS1 Achchuthan Shanmugasundram Source NHS GMS was added to LINS1.
Added phenotypes Intellectual developmental disorder, autosomal recessive 27, OMIM:614340 for gene: LINS1
Publications for gene: LINS1 were updated from to 34450347; 32499722; 39138116; 32802957; 38563234; 28181389; 31922598
Fetal anomalies v5.13 LAMB2 Achchuthan Shanmugasundram gene: LAMB2 was added
gene: LAMB2 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: LAMB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LAMB2 were set to 14136829; 15372515; 17256789
Phenotypes for gene: LAMB2 were set to Pierson syndrome, OMIM:609049
Fetal anomalies v5.13 LAMA5 Achchuthan Shanmugasundram gene: LAMA5 was added
gene: LAMA5 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: LAMA5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LAMA5 were set to 32439764; 35584218; 35419533; 36714636; 37985485
Phenotypes for gene: LAMA5 were set to Nephrotic syndrome, type 26, OMIM:620049
Fetal anomalies v5.13 KPTN Achchuthan Shanmugasundram Source NHS GMS was added to KPTN.
Publications for gene: KPTN were updated from to 39083632
Fetal anomalies v5.13 KMT2B Achchuthan Shanmugasundram Source NHS GMS was added to KMT2B.
Mode of inheritance for gene KMT2B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Intellectual developmental disorder, autosomal dominant 68, OMIM:619934 for gene: KMT2B
Publications for gene: KMT2B were updated from to 29276005; 29697234; 33150406
Fetal anomalies v5.13 KIF5B Achchuthan Shanmugasundram gene: KIF5B was added
gene: KIF5B was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: KIF5B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF5B were set to 36018820; 35342932
Phenotypes for gene: KIF5B were set to kyphomelic dysplasia, MONDO:0008881
Fetal anomalies v5.13 KIF26A Achchuthan Shanmugasundram gene: KIF26A was added
gene: KIF26A was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: KIF26A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF26A were set to 36564622
Phenotypes for gene: KIF26A were set to Cortical dysplasia, complex, with other brain malformations 11, OMIM:620156
Fetal anomalies v5.13 KIF24 Achchuthan Shanmugasundram gene: KIF24 was added
gene: KIF24 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: KIF24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF24 were set to 35748595
Phenotypes for gene: KIF24 were set to skeletal dysplasia, MONDO:0018230
Fetal anomalies v5.13 KDR Achchuthan Shanmugasundram gene: KDR was added
gene: KDR was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: KDR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KDR were set to 28991257; 34113005; 30232381
Phenotypes for gene: KDR were set to Hemangioma, capillary infantile, somatic, OMIM:602089
Fetal anomalies v5.13 KDM5A Achchuthan Shanmugasundram gene: KDM5A was added
gene: KDM5A was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: KDM5A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: KDM5A were set to 33350388; 21937992
Phenotypes for gene: KDM5A were set to El Hayek-Chahrour neurodevelopmental syndrome, OMIM:620820
Fetal anomalies v5.13 KDM2B Achchuthan Shanmugasundram gene: KDM2B was added
gene: KDM2B was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: KDM2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KDM2B were set to 36322151
Phenotypes for gene: KDM2B were set to Neurodevelopmental disorder MONDO:0700092, KDM2B-related
Fetal anomalies v5.13 KDELR2 Achchuthan Shanmugasundram gene: KDELR2 was added
gene: KDELR2 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: KDELR2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KDELR2 were set to 33053334
Phenotypes for gene: KDELR2 were set to Osteogenesis imperfecta, type XXI, OMIM:619131
Fetal anomalies v5.13 KCNT1 Achchuthan Shanmugasundram Source NHS GMS was added to KCNT1.
Mode of pathogenicity for gene KCNT1 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Added phenotypes Developmental and epileptic encephalopathy 14, OMIM:614959 for gene: KCNT1
Publications for gene: KCNT1 were updated from to 36307859
Fetal anomalies v5.13 KCNN3 Achchuthan Shanmugasundram gene: KCNN3 was added
gene: KCNN3 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: KCNN3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNN3 were set to 31155282; 33594261
Phenotypes for gene: KCNN3 were set to Zimmermann-Laband syndrome 3, OMIM:618658
Mode of pathogenicity for gene: KCNN3 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Fetal anomalies v5.13 KCNK9 Achchuthan Shanmugasundram Source NHS GMS was added to KCNK9.
Fetal anomalies v5.13 KCNK3 Achchuthan Shanmugasundram gene: KCNK3 was added
gene: KCNK3 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: KCNK3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNK3 were set to 36195757
Phenotypes for gene: KCNK3 were set to Neurodevelopmental disorder, MONDO:0700092, KCNK3-related
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
Fetal anomalies v5.13 KCNJ6 Achchuthan Shanmugasundram Source NHS GMS was added to KCNJ6.
Source Expert Review Red was added to KCNJ6.
Mode of inheritance for gene KCNJ6 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mode of pathogenicity for gene KCNJ6 was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Added phenotypes Keppen-Lubinsky syndrome, OMIM:614098 for gene: KCNJ6
Publications for gene: KCNJ6 were updated from to 34964963; 36071510; 25620207; 29852244
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Fetal anomalies v5.13 KCNC3 Achchuthan Shanmugasundram Source NHS GMS was added to KCNC3.
Mode of inheritance for gene KCNC3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Spinocerebellar ataxia 13, OMIM:605259 for gene: KCNC3
Publications for gene: KCNC3 were updated from to 20301404
Fetal anomalies v5.13 ITCH Achchuthan Shanmugasundram Source NHS GMS was added to ITCH.
Source Expert Review Red was added to ITCH.
Added phenotypes Autoimmune disease, multisystem, with facial dysmorphism, OMIM:613385 for gene: ITCH
Publications for gene: ITCH were updated from to 20170897; 31091003
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Fetal anomalies v5.13 INTS13 Achchuthan Shanmugasundram gene: INTS13 was added
gene: INTS13 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: INTS13 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS13 were set to 36229431
Phenotypes for gene: INTS13 were set to orofaciodigital syndrome, MONDO:0015375
Fetal anomalies v5.13 INTS11 Achchuthan Shanmugasundram gene: INTS11 was added
gene: INTS11 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: INTS11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS11 were set to 37054711; 39030370
Phenotypes for gene: INTS11 were set to Neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities, OMIM:620428
Fetal anomalies v5.13 INPP5K Achchuthan Shanmugasundram Source NHS GMS was added to INPP5K.
Added phenotypes Muscular dystrophy, congenital, with cataracts and intellectual disability, OMIM:617404 for gene: INPP5K
Publications for gene: INPP5K were updated from to 28190456; 33193651; 28940338; 28190459; 31630891
Fetal anomalies v5.13 IL1RN Achchuthan Shanmugasundram gene: IL1RN was added
gene: IL1RN was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: IL1RN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL1RN were set to 19494219; 19494218
Phenotypes for gene: IL1RN were set to Interleukin 1 receptor antagonist deficiency, OMIM:612852
Fetal anomalies v5.13 IDH2 Achchuthan Shanmugasundram gene: IDH2 was added
gene: IDH2 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: IDH2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: IDH2 were set to 20847235; 38782764
Phenotypes for gene: IDH2 were set to D-2-hydroxyglutaric aciduria 2, OMIM:613657
Fetal anomalies v5.13 HECTD4 Achchuthan Shanmugasundram gene: HECTD4 was added
gene: HECTD4 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: HECTD4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HECTD4 were set to 36401616
Phenotypes for gene: HECTD4 were set to Neurodevelopmental disorder with seizures, spasticity, and complete or partial agenesis of the corpus callosum, OMIM:620250
Fetal anomalies v5.13 HEATR3 Achchuthan Shanmugasundram gene: HEATR3 was added
gene: HEATR3 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: HEATR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HEATR3 were set to 35213692
Phenotypes for gene: HEATR3 were set to Diamond-Blackfan anemia 21, OMIM:620072
Fetal anomalies v5.13 GTPBP1 Achchuthan Shanmugasundram gene: GTPBP1 was added
gene: GTPBP1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: GTPBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GTPBP1 were set to 38118446
Phenotypes for gene: GTPBP1 were set to Neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1, OMIM:620888
Fetal anomalies v5.13 GPC4 Achchuthan Shanmugasundram gene: GPC4 was added
gene: GPC4 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: GPC4 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: GPC4 were set to 9001804; 21567928; 30982611; 17726694; 12605449; 4708024; 18541962
Phenotypes for gene: GPC4 were set to Keipert syndrome, OMIM:301026
Fetal anomalies v5.13 GPAA1 Achchuthan Shanmugasundram Source NHS GMS was added to GPAA1.
Source Expert Review Red was added to GPAA1.
Added phenotypes Glycosylphosphatidylinositol biosynthesis defect 15, OMIM:617810 for gene: GPAA1
Publications for gene: GPAA1 were updated from to 37510348; 34703884; 29100095; 39152716
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Fetal anomalies v5.13 GON4L Achchuthan Shanmugasundram gene: GON4L was added
gene: GON4L was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: GON4L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GON4L were set to 39500882
Phenotypes for gene: GON4L were set to complex neurodevelopmental disorder, MONDO:0100038
Fetal anomalies v5.13 GNB2 Achchuthan Shanmugasundram Source NHS GMS was added to GNB2.
Publications for gene: GNB2 were updated from 31698099; 34183358; 36658419 to 31698099; 36658419; 34183358
Fetal anomalies v5.13 GNAQ Achchuthan Shanmugasundram Source NHS GMS was added to GNAQ.
Source Expert Review Red was added to GNAQ.
Added phenotypes Sturge-Weber syndrome, somatic, mosaic, OMIM:185300; Capillary malformations, congenital, 1, somatic, mosaic, OMIM:163000 for gene: GNAQ
Publications for gene: GNAQ were updated from to 23656586; 37606556; 36263782
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Fetal anomalies v5.13 GNAI1 Achchuthan Shanmugasundram Source NHS GMS was added to GNAI1.
Source Expert Review Red was added to GNAI1.
Publications for gene: GNAI1 were updated from to 34819662; 38441201; 39083633; 33473207; 34685729
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Fetal anomalies v5.13 GNA14 Achchuthan Shanmugasundram Source NHS GMS was added to GNA14.
Publications for gene: GNA14 were updated from to 38917801
Fetal anomalies v5.13 GNA11 Achchuthan Shanmugasundram Source NHS GMS was added to GNA11.
Added phenotypes Hypocalciuric hypercalcemia, type II, OMIM:145981; Hypocalcemia, autosomal dominant 2, OMIM:615361 for gene: GNA11
Publications for gene: GNA11 were updated from to 27438697
Fetal anomalies v5.13 GLIS2 Achchuthan Shanmugasundram Source NHS GMS was added to GLIS2.
Source Expert Review Red was added to GLIS2.
Added phenotypes Nephronophthisis 7, OMIM:611498 for gene: GLIS2
Publications for gene: GLIS2 were updated from to 17618285; 23559409; 31676329
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Fetal anomalies v5.13 GDF2 Achchuthan Shanmugasundram Source NHS GMS was added to GDF2.
Source Expert Review Amber was added to GDF2.
Mode of inheritance for gene GDF2 was changed from BIALLELIC, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Telangiectasia, hereditary hemorrhagic, type 5, OMIM:615506 for gene: GDF2
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Fetal anomalies v5.13 GALNT3 Achchuthan Shanmugasundram gene: GALNT3 was added
gene: GALNT3 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: GALNT3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GALNT3 were set to Tumoral calcinosis, hyperphosphatemic, familial, 1, OMIM:211900
Fetal anomalies v5.13 FZD6 Achchuthan Shanmugasundram Source NHS GMS was added to FZD6.
Fetal anomalies v5.13 FZD5 Achchuthan Shanmugasundram Source NHS GMS was added to FZD5.
Source Expert Review Red was added to FZD5.
Mode of inheritance for gene FZD5 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FZD5 were updated from to 33633439; 36695497; 32737437; 26908622
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Fetal anomalies v5.13 FUZ Achchuthan Shanmugasundram Source NHS GMS was added to FUZ.
Source Expert Review Amber was added to FUZ.
Mode of inheritance for gene FUZ was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Skeletal ciliopathy, MONDO:0005308 for gene: FUZ
Publications for gene: FUZ were updated from to 29068549; 34719684; 38702430
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Fetal anomalies v5.13 FTO Achchuthan Shanmugasundram Source NHS GMS was added to FTO.
Added phenotypes Growth retardation, developmental delay, facial dysmorphism, OMIM: 612938 for gene: FTO
Publications for gene: FTO were updated from 19559399; 26378117; 31130284 to 19234441; 26697951; 26378117; 19559399; 26740239; 31130284
Fetal anomalies v5.13 FRYL Achchuthan Shanmugasundram gene: FRYL was added
gene: FRYL was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: FRYL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FRYL were set to 38479391
Phenotypes for gene: FRYL were set to Neurodevelopmental disorder, MONDO:0700092, FRYL-related
Fetal anomalies v5.13 FOXP4 Achchuthan Shanmugasundram Source NHS GMS was added to FOXP4.
Added phenotypes Congenital diaphragmatic hernia for gene: FOXP4
Publications for gene: FOXP4 were updated from 33110267 to 33110267; 36301021
Fetal anomalies v5.13 FOXI3 Achchuthan Shanmugasundram gene: FOXI3 was added
gene: FOXI3 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: FOXI3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: FOXI3 were set to 25655429; 36260083; 37041148
Phenotypes for gene: FOXI3 were set to Craniofacial microsomia 2, OMIM:620444
Fetal anomalies v5.13 FOSL2 Achchuthan Shanmugasundram gene: FOSL2 was added
gene: FOSL2 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: FOSL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOSL2 were set to 36197437
Phenotypes for gene: FOSL2 were set to Aplasia cutis-enamel dysplasia syndrome, OMIM:620789
Fetal anomalies v5.13 FN1 Achchuthan Shanmugasundram Source NHS GMS was added to FN1.
Added phenotypes Spondylometaphyseal dysplasia, corner fracture type, OMIM:184255 for gene: FN1
Publications for gene: FN1 were updated from to 32200603
Fetal anomalies v5.13 FLCN Achchuthan Shanmugasundram gene: FLCN was added
gene: FLCN was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: FLCN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FLCN were set to 19785621; 31266032
Phenotypes for gene: FLCN were set to Birt-Hogg-Dube syndrome, 135150; Pneumothorax, primary spontaneous, OMIM:173600
Fetal anomalies v5.13 FILIP1 Achchuthan Shanmugasundram gene: FILIP1 was added
gene: FILIP1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: FILIP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FILIP1 were set to 36943452; 37163662
Phenotypes for gene: FILIP1 were set to Neuromuscular disorder, congenital, with dysmorphic facies, OMIM:620775
Fetal anomalies v5.13 FGF23 Achchuthan Shanmugasundram gene: FGF23 was added
gene: FGF23 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: FGF23 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: FGF23 were set to Tumoral calcinosis, hyperphosphatemic, familial, OMIM:6211900; Hypophosphatemic rickets, autosomal dominant, OMIM:6193100
Fetal anomalies v5.13 FGF16 Achchuthan Shanmugasundram gene: FGF16 was added
gene: FGF16 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: FGF16 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: FGF16 were set to 25333065; 24706454; 23709756
Phenotypes for gene: FGF16 were set to Metacarpal 4-5 fusion, OMIM:309630
Fetal anomalies v5.13 FERMT3 Achchuthan Shanmugasundram gene: FERMT3 was added
gene: FERMT3 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: FERMT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FERMT3 were set to 19064721; 19234460
Phenotypes for gene: FERMT3 were set to Leukocyte adhesion deficiency, type III OMIM:612840
Fetal anomalies v5.13 FAS Achchuthan Shanmugasundram gene: FAS was added
gene: FAS was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: FAS was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: FAS were set to 39384643
Phenotypes for gene: FAS were set to Autoimmune lymphoproliferative syndrome, type IA, OMIM:601859
Fetal anomalies v5.13 EXPH5 Achchuthan Shanmugasundram Source NHS GMS was added to EXPH5.
Source Expert Review Red was added to EXPH5.
Added phenotypes Epidermolysis bullosa simplex 4, localized or generalized intermediate, autosomal recessive, OMIM:615028 for gene: EXPH5
Publications for gene: EXPH5 were updated from to 24443915; 23176819; 32176379; 24005056; 27730671; 27384765
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Fetal anomalies v5.13 ESAM Achchuthan Shanmugasundram Source NHS GMS was added to ESAM.
Publications for gene: ESAM were updated from 36996813 to 39414991; 36996813
Fetal anomalies v5.13 ERI1 Achchuthan Shanmugasundram gene: ERI1 was added
gene: ERI1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: ERI1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERI1 were set to 36208065; 37352860; 28488351; 33942433
Phenotypes for gene: ERI1 were set to Spondyloepimetaphyseal dysplasia, Guo-Campeau type, OMIM:620663; Hoxha-Aliu syndrome, OMIM:620662
Fetal anomalies v5.13 ENG Achchuthan Shanmugasundram Source NHS GMS was added to ENG.
Publications for gene: ENG were updated from to 36588762; 32954511; 15520401
Fetal anomalies v5.13 EMILIN1 Achchuthan Shanmugasundram gene: EMILIN1 was added
gene: EMILIN1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: EMILIN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EMILIN1 were set to 14701737; 36351433
Phenotypes for gene: EMILIN1 were set to Arterial tortuosity-bone fragility syndrome, OMIM:620908
Fetal anomalies v5.13 EMG1 Achchuthan Shanmugasundram Source NHS GMS was added to EMG1.
Fetal anomalies v5.13 EIF3B Achchuthan Shanmugasundram gene: EIF3B was added
gene: EIF3B was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: EIF3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: EIF3B were set to Single kidney; Bilateral cleft lip and palate; Tetralogy of Fallot; Asplenia
Fetal anomalies v5.13 EFEMP1 Achchuthan Shanmugasundram gene: EFEMP1 was added
gene: EFEMP1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: EFEMP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EFEMP1 were set to 33807164; 17872905; 22489068; 32006683; 31792352
Phenotypes for gene: EFEMP1 were set to Cutis laxa, autosomal recessive, type ID, OMIM:620780
Fetal anomalies v5.13 EFCAB1 Achchuthan Shanmugasundram gene: EFCAB1 was added
gene: EFCAB1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: EFCAB1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EFCAB1 were set to 36727596
Phenotypes for gene: EFCAB1 were set to Ciliary dyskinesia, primary, 53, OMIM:620642
Fetal anomalies v5.13 DVL2 Achchuthan Shanmugasundram gene: DVL2 was added
gene: DVL2 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: DVL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DVL2 were set to 35047859; 33599851; 30521570
Phenotypes for gene: DVL2 were set to Robinow syndrome, MONDO:0019978
Fetal anomalies v5.13 DRG1 Achchuthan Shanmugasundram gene: DRG1 was added
gene: DRG1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: DRG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DRG1 were set to 37179472
Phenotypes for gene: DRG1 were set to Tan-Almurshedi syndrome, OMIM:620641
Fetal anomalies v5.13 DRC1 Achchuthan Shanmugasundram Source NHS GMS was added to DRC1.
Added phenotypes Ciliary dyskinesia, primary, 21, OMIM:615294 for gene: DRC1
Publications for gene: DRC1 were updated from to 39152285; 39462806; 34851034
Fetal anomalies v5.13 DPYSL5 Achchuthan Shanmugasundram gene: DPYSL5 was added
gene: DPYSL5 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: DPYSL5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DPYSL5 were set to 33894126
Phenotypes for gene: DPYSL5 were set to Ritscher-Schinzel syndrome 4, OMIM:619435
Fetal anomalies v5.13 DOHH Achchuthan Shanmugasundram gene: DOHH was added
gene: DOHH was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: DOHH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOHH were set to 35858628
Phenotypes for gene: DOHH were set to Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment, OMIM:620066
Fetal anomalies v5.13 DLX3 Achchuthan Shanmugasundram gene: DLX3 was added
gene: DLX3 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: DLX3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DLX3 were set to 26104267; 26762616
Phenotypes for gene: DLX3 were set to Amelogenesis imperfecta, type IV, OMIM:104510; Trichodontoosseous syndrome, OMIM:190320
Fetal anomalies v5.13 DLG5 Achchuthan Shanmugasundram gene: DLG5 was added
gene: DLG5 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: DLG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DLG5 were set to 32631816; 30791088
Phenotypes for gene: DLG5 were set to Yuksel-Vogel-Bauser syndrome, OMIM:620703
Fetal anomalies v5.13 DLG4 Achchuthan Shanmugasundram Source NHS GMS was added to DLG4.
Mode of inheritance for gene DLG4 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Intellectual developmental disorder, autosomal dominant 62, OMIM:618793 for gene: DLG4
Publications for gene: DLG4 were updated from to 37347881
Fetal anomalies v5.13 DHX30 Achchuthan Shanmugasundram Source NHS GMS was added to DHX30.
Mode of inheritance for gene DHX30 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Neurodevelopmental disorder with variable motor and speech impairment, OMIM:617804 for gene: DHX30
Publications for gene: DHX30 were updated from to 34020708; 38366977; 34145223; 34180050; 37094863; 36643085
Fetal anomalies v5.13 DDRGK1 Achchuthan Shanmugasundram gene: DDRGK1 was added
gene: DDRGK1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: DDRGK1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDRGK1 were set to 35670300; 35377455; 28263186; 36243336
Phenotypes for gene: DDRGK1 were set to Spondyloepimetaphyseal dysplasia, Shohat type, OMIM:602557
Fetal anomalies v5.13 DCDC2 Achchuthan Shanmugasundram Source NHS GMS was added to DCDC2.
Added phenotypes Sclerosing cholangitis, neonatal, OMIM:617394 for gene: DCDC2
Publications for gene: DCDC2 were updated from to 37296768; 36816379; 36938759; 35570614; 34155636
Fetal anomalies v5.13 DAW1 Achchuthan Shanmugasundram gene: DAW1 was added
gene: DAW1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: DAW1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DAW1 were set to 36074124; 28991257
Phenotypes for gene: DAW1 were set to Ciliary dyskinesia, primary, 52, OMIM:620570
Fetal anomalies v5.13 CYP2R1 Achchuthan Shanmugasundram gene: CYP2R1 was added
gene: CYP2R1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: CYP2R1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP2R1 were set to 28548312; 15128933
Phenotypes for gene: CYP2R1 were set to Rickets due to defect in vitamin D 25-hydroxylation deficiency, OMIM:600081
Fetal anomalies v5.13 CYP27B1 Achchuthan Shanmugasundram gene: CYP27B1 was added
gene: CYP27B1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: CYP27B1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYP27B1 were set to 34492747; 9486994; 27473561; 12050193; 9415400; 33823104
Phenotypes for gene: CYP27B1 were set to Vitamin D-dependent rickets, type I, OMIM:264700
Fetal anomalies v5.13 CYB5R3 Achchuthan Shanmugasundram Source NHS GMS was added to CYB5R3.
Added phenotypes Methemoglobinemia, type II, OMIM:250800 for gene: CYB5R3
Publications for gene: CYB5R3 were updated from to 34467556
Fetal anomalies v5.13 CUL3 Achchuthan Shanmugasundram gene: CUL3 was added
gene: CUL3 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: CUL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CUL3 were set to 31512373; 31145527; 28135719
Phenotypes for gene: CUL3 were set to Neurodevelopmental disorder with or without autism or seizures, OMIM:619239; Pseudohypoaldosteronism, type IIE, OMIM:614496
Fetal anomalies v5.13 CTSC Achchuthan Shanmugasundram gene: CTSC was added
gene: CTSC was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: CTSC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTSC were set to 32601924; 14974080; 11106356; 10581027; 10662808
Phenotypes for gene: CTSC were set to Papillon-Lefevre syndrome, OMIM:245000; Haim-Munk syndrome, OMIM:245010
Fetal anomalies v5.13 CSTA Achchuthan Shanmugasundram Source NHS GMS was added to CSTA.
Source Expert Review Red was added to CSTA.
Added phenotypes Peeling skin syndrome 4, OMIM:607936 for gene: CSTA
Publications for gene: CSTA were updated from to 21944047; 12890214; 25400170; 22066523
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Fetal anomalies v5.13 CSMD1 Achchuthan Shanmugasundram gene: CSMD1 was added
gene: CSMD1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: CSMD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSMD1 were set to 38816421
Phenotypes for gene: CSMD1 were set to Complex neurodevelopmental disorder, MONDO:0100038
Fetal anomalies v5.13 CSGALNACT1 Achchuthan Shanmugasundram gene: CSGALNACT1 was added
gene: CSGALNACT1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: CSGALNACT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSGALNACT1 were set to 31705726; 31325655
Phenotypes for gene: CSGALNACT1 were set to Skeletal dysplasia, mild, with joint laxity and advanced bone age, OMIM:618870
Fetal anomalies v5.13 CRELD1 Achchuthan Shanmugasundram Source NHS GMS was added to CRELD1.
Mode of inheritance for gene CRELD1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Jeffries-Lakhani neurodevelopmental syndrome, OMIM:620771 for gene: CRELD1
Publications for gene: CRELD1 were updated from to 37947183
Fetal anomalies v5.13 COPB2 Achchuthan Shanmugasundram gene: COPB2 was added
gene: COPB2 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: COPB2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: COPB2 were set to 34450031; 29036432
Phenotypes for gene: COPB2 were set to ?Microcephaly 19, primary, autosomal recessive, OMIM:617800; Osteoporosis, childhood- or juvenile-onset, with developmental delay, OMIM:619884
Fetal anomalies v5.13 CNOT2 Achchuthan Shanmugasundram gene: CNOT2 was added
gene: CNOT2 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: CNOT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CNOT2 were set to 31512373; 31145527; 28135719
Phenotypes for gene: CNOT2 were set to Intellectual developmental disorder with nasal speech, dysmorphic facies, and variable skeletal anomalies, OMIM:618608
Fetal anomalies v5.13 CLPP Achchuthan Shanmugasundram Source NHS GMS was added to CLPP.
Added phenotypes Perrault syndrome 3, OMIM:614129 for gene: CLPP
Publications for gene: CLPP were updated from to 38454547; 37932750; 34338890; 38249302
Fetal anomalies v5.13 CLCN5 Achchuthan Shanmugasundram Source NHS GMS was added to CLCN5.
Publications for gene: CLCN5 were updated from 36307859; 36495297; 37229200 to 36495297; 38267993; 36307859; 37229200
Fetal anomalies v5.13 CHD8 Achchuthan Shanmugasundram Source NHS GMS was added to CHD8.
Mode of inheritance for gene CHD8 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Intellectual developmental disorder with autism and macrocephaly, OMIM:615032 for gene: CHD8
Publications for gene: CHD8 were updated from to 31980904
Fetal anomalies v5.13 CHD3 Achchuthan Shanmugasundram Source NHS GMS was added to CHD3.
Mode of inheritance for gene CHD3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Snijders Blok-Campeau syndrome, OMIM:618205 for gene: CHD3
Publications for gene: CHD3 were updated from to 32483341; 39050258; 30397230; 37761804
Fetal anomalies v5.13 CEP295 Achchuthan Shanmugasundram gene: CEP295 was added
gene: CEP295 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: CEP295 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP295 were set to 38154379
Phenotypes for gene: CEP295 were set to Seckel syndrome 11, OMIM:620767
Fetal anomalies v5.13 CELSR3 Achchuthan Shanmugasundram gene: CELSR3 was added
gene: CELSR3 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: CELSR3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CELSR3 were set to 38429302
Phenotypes for gene: CELSR3 were set to Neurodevelopmental disorder, MONDO:0700092, CELSR3-related
Fetal anomalies v5.13 CDK10 Achchuthan Shanmugasundram gene: CDK10 was added
gene: CDK10 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: CDK10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK10 were set to 34974531; 28886341
Phenotypes for gene: CDK10 were set to Al Kaissi syndrome, OMIM:617694
Fetal anomalies v5.13 CDH2 Achchuthan Shanmugasundram gene: CDH2 was added
gene: CDH2 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: CDH2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CDH2 were set to 31650526; 31585109
Phenotypes for gene: CDH2 were set to Agenesis of corpus callosum, cardiac, ocular, and genital syndrome, OMIM:618929
Fetal anomalies v5.13 CD40LG Achchuthan Shanmugasundram gene: CD40LG was added
gene: CD40LG was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: CD40LG was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CD40LG were set to 8993019; 10228294; 14451053; 24631270; 35572607; 6605368; 9255191
Phenotypes for gene: CD40LG were set to Immunodeficiency, X-linked, with hyper-IgM, OMIM:308230
Fetal anomalies v5.13 CD151 Achchuthan Shanmugasundram Source NHS GMS was added to CD151.
Source Expert Review Red was added to CD151.
Added phenotypes Epidermolysis bullosa simplex 7, with nephropathy and deafness, OMIM:609057 for gene: CD151
Publications for gene: CD151 were updated from to 35519797; 20301543
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Fetal anomalies v5.13 CBY1 Achchuthan Shanmugasundram gene: CBY1 was added
gene: CBY1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: CBY1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CBY1 were set to 33131181; 25220153; 25103236
Phenotypes for gene: CBY1 were set to Intellectual disability; Joubert syndrome; Cerebellar ataxia; Polydactyly; Molar tooth sign
Fetal anomalies v5.13 CASP2 Achchuthan Shanmugasundram gene: CASP2 was added
gene: CASP2 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: CASP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CASP2 were set to 37880421
Phenotypes for gene: CASP2 were set to Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly, OMIM:620653
Fetal anomalies v5.13 CAPRIN1 Achchuthan Shanmugasundram gene: CAPRIN1 was added
gene: CAPRIN1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: CAPRIN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAPRIN1 were set to 35979925
Phenotypes for gene: CAPRIN1 were set to Neurodevelopmental disorder with language impairment, autism, and attention deficit-hyperactivity disorder, OMIM:620782
Fetal anomalies v5.13 CAMTA1 Achchuthan Shanmugasundram Source NHS GMS was added to CAMTA1.
Mode of inheritance for gene CAMTA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Cerebellar dysfunction with variable cognitive and behavioral abnormalities, OMIM:614756 for gene: CAMTA1
Publications for gene: CAMTA1 were updated from to 38044714
Fetal anomalies v5.13 CAMK2B Achchuthan Shanmugasundram Source NHS GMS was added to CAMK2B.
Mode of inheritance for gene CAMK2B was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Intellectual developmental disorder, autosomal dominant 54, OMIM:617799 for gene: CAMK2B
Publications for gene: CAMK2B were updated from to 37734707; 29100089; 29560374
Fetal anomalies v5.13 CACNA1S Achchuthan Shanmugasundram Source NHS GMS was added to CACNA1S.
Added phenotypes Congenital myopathy 18 due to dihydropyridine receptor defect, OMIM:620246 for gene: CACNA1S
Publications for gene: CACNA1S were updated from 28012042; 33060286 to 28012042; 38111203; 33060286
Fetal anomalies v5.13 CACHD1 Achchuthan Shanmugasundram Source NHS GMS was added to CACHD1.
Fetal anomalies v5.13 C1GALT1C1 Achchuthan Shanmugasundram gene: C1GALT1C1 was added
gene: C1GALT1C1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: C1GALT1C1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: C1GALT1C1 were set to 36599939; 37216524
Phenotypes for gene: C1GALT1C1 were set to Hemolytic uremic syndrome, atypical, 8, with rhizomelic short stature, OMIM:301110
Fetal anomalies v5.13 C16orf62 Achchuthan Shanmugasundram gene: C16orf62 was added
gene: C16orf62 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: C16orf62 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: C16orf62 were set to 36113987
Phenotypes for gene: C16orf62 were set to Ritscher-Schinzel syndrome 3, OMIM:619135
Fetal anomalies v5.13 BPTF Achchuthan Shanmugasundram Source NHS GMS was added to BPTF.
Source Expert Review Red was added to BPTF.
Mode of inheritance for gene BPTF was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies, OMIM:617755 for gene: BPTF
Publications for gene: BPTF were updated from to 33522091; 36153657
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Fetal anomalies v5.13 AXIN1 Achchuthan Shanmugasundram gene: AXIN1 was added
gene: AXIN1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: AXIN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AXIN1 were set to 37582359
Phenotypes for gene: AXIN1 were set to Craniometadiaphyseal osteosclerosis with hip dysplasia, OMIM:620558
Fetal anomalies v5.13 ATG7 Achchuthan Shanmugasundram gene: ATG7 was added
gene: ATG7 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: ATG7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATG7 were set to 17726112; 16625205; 34161705
Phenotypes for gene: ATG7 were set to Spinocerebellar ataxia, autosomal recessive 31, OMIM:619422
Fetal anomalies v5.13 ASXL3 Achchuthan Shanmugasundram Source NHS GMS was added to ASXL3.
Mode of inheritance for gene ASXL3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ASXL3 were updated from 29316359; 32565546; 33820833 to 38420660; 33820833; 32565546; 29316359
Fetal anomalies v5.13 ASPH Achchuthan Shanmugasundram Source NHS GMS was added to ASPH.
Source Expert Review Red was added to ASPH.
Publications for gene: ASPH were updated from 28976722 to 30194805; 24768550; 23687502; 11241487; 8749053; 28976722
Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Fetal anomalies v5.13 ASCC3 Achchuthan Shanmugasundram gene: ASCC3 was added
gene: ASCC3 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: ASCC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASCC3 were set to 35047834; 21937992
Phenotypes for gene: ASCC3 were set to Intellectual developmental disorder, autosomal recessive 81, OMIM:620700
Fetal anomalies v5.13 ARV1 Achchuthan Shanmugasundram Source NHS GMS was added to ARV1.
Publications for gene: ARV1 were updated from 34296759; 36307859 to 36307859; 34296759
Fetal anomalies v5.13 AMOTL1 Achchuthan Shanmugasundram gene: AMOTL1 was added
gene: AMOTL1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: AMOTL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AMOTL1 were set to 36751037
Phenotypes for gene: AMOTL1 were set to Orofacial clefting syndrome, MONDO:0015335, AMOTL1-related
Mode of pathogenicity for gene: AMOTL1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Fetal anomalies v5.13 ALG5 Achchuthan Shanmugasundram gene: ALG5 was added
gene: ALG5 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Red
Mode of inheritance for gene: ALG5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALG5 were set to 35896117
Phenotypes for gene: ALG5 were set to Polycystic kidney disease 7, OMIM:620056
Fetal anomalies v5.13 ALG13 Achchuthan Shanmugasundram Source NHS GMS was added to ALG13.
Added phenotypes Developmental and epileptic encephalopathy 36, OMIM:300884 for gene: ALG13
Publications for gene: ALG13 were updated from to 32681751
Fetal anomalies v5.13 ALG11 Achchuthan Shanmugasundram Source NHS GMS was added to ALG11.
Added phenotypes Congenital disorder of glycosylation, type Ip, OMIM:613661 for gene: ALG11
Publications for gene: ALG11 were updated from to 30770273
Fetal anomalies v5.13 AL117258.1 Achchuthan Shanmugasundram gene: AL117258.1 was added
gene: AL117258.1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: AL117258.1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AL117258.1 were set to 34903892; 39513328
Phenotypes for gene: AL117258.1 were set to Heterotaxy, visceral, 12, autosomal, OMIM:619702
Fetal anomalies v5.13 ADD1 Achchuthan Shanmugasundram gene: ADD1 was added
gene: ADD1 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: ADD1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ADD1 were set to 34906466
Phenotypes for gene: ADD1 were set to Neurodevelopmental disorder, MONDO:0700092, ADD1-related
Fetal anomalies v5.13 ADAMTS15 Achchuthan Shanmugasundram gene: ADAMTS15 was added
gene: ADAMTS15 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: ADAMTS15 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAMTS15 were set to 35962790
Phenotypes for gene: ADAMTS15 were set to Arthrogryposis, distal, type 12, OMIM:620545
Fetal anomalies v5.13 ACBD6 Achchuthan Shanmugasundram gene: ACBD6 was added
gene: ACBD6 was added to Fetal anomalies. Sources: NHS GMS,Expert Review Amber
Mode of inheritance for gene: ACBD6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACBD6 were set to 37951597; 36457943; 34296759
Phenotypes for gene: ACBD6 were set to Neurodevelopmental disorder with progressive movement abnormalities, OMIM:620785
Fetal anomalies v5.13 ABCD4 Achchuthan Shanmugasundram Source NHS GMS was added to ABCD4.
Publications for gene: ABCD4 were updated from to 33729671
Congenital hypothyroidism v2.22 TPO Arina Puzriakova Phenotypes for gene: TPO were changed from Congenital hypothyroidism; Thyroid dyshormonogenesis 2A, 274500; TDH2A; Iodide organification defect; goitre to Thyroid dyshormonogenesis 2A, OMIM:274500
Congenital hypothyroidism v2.21 TPO Arina Puzriakova Added comment: Comment on publications: PMID: 39890415 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI
Congenital hypothyroidism v2.21 TPO Arina Puzriakova Publications for gene: TPO were set to 12938097; 8027236; 8964831; 11061528; 27525530 (Nicholas et al.,2016) identify a monogenic basis of disease; 27166716
Intellectual disability v8.96 GABBR2 Arina Puzriakova Added comment: Comment on publications: PMID: 39028675 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI
Intellectual disability v8.96 GABBR2 Arina Puzriakova Publications for gene: GABBR2 were set to 29100083; 28061363; 28135719; 28856709; 29369404; 29377213; 39028675
Early onset or syndromic epilepsy v7.37 GABBR2 Arina Puzriakova Added comment: Comment on publications: PMID: 39028675 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI
Early onset or syndromic epilepsy v7.37 GABBR2 Arina Puzriakova Publications for gene: GABBR2 were set to 29100083; 28061363; 28135719; 28856709; 39028675
Intellectual disability v8.95 GABBR2 Arina Puzriakova Publications for gene: GABBR2 were set to 29100083; 28061363; 28135719; 28856709; 29369404; 29377213
Early onset or syndromic epilepsy v7.36 GABBR2 Arina Puzriakova Publications for gene: GABBR2 were set to EuroEPINOMICS-RES Consortium (2014) AJHG 95:1-11; 29100083; 28061363; 28135719; 28856709
Intellectual disability v8.94 GABBR2 Arina Puzriakova Phenotypes for gene: GABBR2 were changed from EPILEPTIC ENCEPHALOPATHY; Rett syndrome; Neurodevelopmental disorder with poor language and loss of hand skills, 617903 to Developmental and epileptic encephalopathy 59, OMIM:617904; eurodevelopmental disorder with poor language and loss of hand skills, OMIM:617903
Early onset or syndromic epilepsy v7.35 GABBR2 Arina Puzriakova Phenotypes for gene: GABBR2 were changed from EPILEPTIC ENCEPHALOPATHY; Rett syndrome; Epileptic encephalopathy, early infantile, 59, 617904 to Developmental and epileptic encephalopathy 59, OMIM:617904
Childhood onset hereditary spastic paraplegia v7.4 SPTSSA Sarah Leigh Phenotypes for gene: SPTSSA were changed from Spastic paraplegia 90A, autosomal dominant, OMIM:620416; ?Spastic paraplegia 90B, autosomal recessive, OMIM:620417 to Spastic paraplegia 90A, autosomal dominant, OMIM:620416; spastic paraplegia 90A, autosomal dominant, MONDO:0957308; ?Spastic paraplegia 90B, autosomal recessive, OMIM:620417
Childhood onset hereditary spastic paraplegia v7.3 SPTSSA Sarah Leigh changed review comment from: The additional report of the de novo occurrence of (NM_138288.4):c.152C>T, p.(Thr51Ile) in a patient has been made by a NHS colleague.; to: The additional report of the de novo occurrence of (NM_138288.4):c.152C>T, p.(Thr51Ile) in a patient has been made by a NHS colleague. Therefore, there have now been three reports of this variant in unrelated cases.
Childhood onset hereditary spastic paraplegia v7.3 SPTSSA Sarah Leigh Tag Q1_25_ promote_green tag was added to gene: SPTSSA.
Childhood onset hereditary spastic paraplegia v7.3 SPTSSA Sarah Leigh reviewed gene: SPTSSA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 90A, autosomal dominant, OMIM:620416, spastic paraplegia 90A, autosomal dominant, MONDO:0957308; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v7.3 SPTSSA Sarah Leigh Publications for gene: SPTSSA were set to 36718090
Intellectual disability v8.93 TARS2 Sarah Leigh Added comment: Comment on publications: PMID: 39394138 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.93 TARS2 Sarah Leigh Publications for gene: TARS2 were set to 39394138; 33153448; 34508595; 37454282
Intellectual disability v8.92 TARS2 Sarah Leigh Classified gene: TARS2 as Amber List (moderate evidence)
Intellectual disability v8.92 TARS2 Sarah Leigh Gene: tars2 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v7.34 TARS2 Sarah Leigh Added comment: Comment on publications: PMID: 39394138 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Early onset or syndromic epilepsy v7.34 TARS2 Sarah Leigh Publications for gene: TARS2 were set to 39394138; 33153448; 34508595; 37454282
Early onset or syndromic epilepsy v7.33 TARS2 Sarah Leigh Classified gene: TARS2 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v7.33 TARS2 Sarah Leigh Gene: tars2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.91 TARS2 Sarah Leigh gene: TARS2 was added
gene: TARS2 was added to Intellectual disability. Sources: Literature
Q1_25_ promote_green tags were added to gene: TARS2.
Mode of inheritance for gene: TARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TARS2 were set to 39394138; 33153448; 34508595; 37454282
Phenotypes for gene: TARS2 were set to Combined oxidative phosphorylation deficiency 21, OMIM: 615918; combined oxidative phosphorylation defect type 21,NDO:0014398
Review for gene: TARS2 was set to GREEN
Added comment: Numerous biallelic TARS2 variants have been associated with Combined oxidative phosphorylation deficiency 21 (OMIM: 615918) in cases from around the world. A summary of TARS2 variants and associated clinical features is presented in Supplementary Table 1, in PMID: 39394138. There at least 30 variants in 32 cases within 27 families. In eight of the families, the children had died before their second birthdays, all of the cases in the remaining 19 families were in special care, with a maximum age of 27 years. Epilepsy was evident in 15/24 families where an assessment was possible, psychomotor delay was evident in 25/26 families and brain MRI anomalies were apparent in 21/23 families.
Sources: Literature
Early onset or syndromic epilepsy v7.32 TARS2 Sarah Leigh gene: TARS2 was added
gene: TARS2 was added to Early onset or syndromic epilepsy. Sources: Literature
Q1_25_ promote_green tags were added to gene: TARS2.
Mode of inheritance for gene: TARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TARS2 were set to 39394138; 33153448; 34508595; 37454282
Phenotypes for gene: TARS2 were set to Combined oxidative phosphorylation deficiency 21, OMIM: 615918; combined oxidative phosphorylation defect type 21,NDO:0014398
Review for gene: TARS2 was set to GREEN
Added comment: Numerous biallelic TARS2 variants have been associated with Combined oxidative phosphorylation deficiency 21 (OMIM: 615918) in cases from around the world. A summary of TARS2 variants and associated clinical features is presented in Supplementary Table 1, in PMID: 39394138. There at least 30 variants in 32 cases within 27 families. In eight of the families, the children had died before their second birthdays, all of the cases in the remaining 19 families were in special care, with a maximum age of 27 years. Epilepsy was evident in 15/24 families where an assessment was possible, psychomotor delay was evident in 25/26 families and brain MRI anomalies were apparent in 21/23 families.
Sources: Literature
Intellectual disability v8.90 OPA1 Sarah Leigh Added comment: Comment on publications: PMID: 39233737 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques
Intellectual disability v8.90 OPA1 Sarah Leigh Publications for gene: OPA1 were set to 39233737
Intellectual disability v8.89 FEM1C Julie Evans changed review comment from: Please note that 'two' of the patients with the heterozygous de novo missense variant c.377A>T p.(Asp126Val) in the FEM1C gene are actually the same South West patient who was recruited to the DDD study (PMID 28135719) and 100,000 genomes project.; to: Please note that the 'two' patients with the heterozygous de novo missense variant c.377A>T p.(Asp126Val) in the FEM1C gene are actually the same South West patient who was recruited to the DDD study (PMID 28135719) and 100,000 genomes project.
Intellectual disability v8.89 FEM1C Julie Evans changed review comment from: Please note that 'two' of the patients with the heterozygous de novo missense variant c.376G>C (p.Asp126His) in the FEM1C gene are actually the same South West patient who was recruited to the DDD study (PMID 28135719) and 100,000 genomes project.; to: Please note that 'two' of the patients with the heterozygous de novo missense variant c.377A>T p.(Asp126Val) in the FEM1C gene are actually the same South West patient who was recruited to the DDD study (PMID 28135719) and 100,000 genomes project.
Intellectual disability v8.89 FEM1C Julie Evans changed review comment from: Please note the 'two' patients with the heterozygous de novo missense variant c.376G>C (p.Asp126His) in the FEM1C gene are actually the same South West patient who was recruited to the DDD study and 100,000 genomes project.; to: Please note that 'two' of the patients with the heterozygous de novo missense variant c.376G>C (p.Asp126His) in the FEM1C gene are actually the same South West patient who was recruited to the DDD study (PMID 28135719) and 100,000 genomes project.
Intellectual disability v8.89 FEM1C Julie Evans reviewed gene: FEM1C: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v8.89 OPA1 Sarah Leigh Classified gene: OPA1 as Amber List (moderate evidence)
Intellectual disability v8.89 OPA1 Sarah Leigh Gene: opa1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.88 OPA1 Sarah Leigh gene: OPA1 was added
gene: OPA1 was added to Intellectual disability. Sources: Literature
Q1_25_ promote_green tags were added to gene: OPA1.
Mode of inheritance for gene: OPA1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: OPA1 were set to 39233737
Phenotypes for gene: OPA1 were set to Optic atrophy plus syndrome, OMIM: 125250
Review for gene: OPA1 was set to GREEN
Added comment: Heterozygous OPA1 variants have been associated with Optic atrophy 1 (OMIM:165500) and Optic atrophy plus syndrome, OMIM: 125250. PMID: 39233737 reports two unrelated cases of OMIM: 125250 with a "prominent neurological phenotype highly resembling clinical and
neuroradiological features of Leigh-like syndrome", including hypotonia and psychomotor delay. Each child had a de novo novel heterozygous OPA1 variant (NM_ 015560.3, c.888T>A, p.Asp296Glu and c.802T>C, p.Tyr268His). The mitochondria in the fibroblasts from these cases appeared to be fragmented with a reduced ATP production compared to controls; additionally, the amount of mtDNA was reduced by about a half in comparison with controls. Complementary studies in yeast suggested that these variants are pathogenic with a possible dominant negative effect (PMID: 39233737).
Sources: Literature
Hypertrophic cardiomyopathy v4.21 MT-TI Achchuthan Shanmugasundram Classified gene: MT-TI as Amber List (moderate evidence)
Hypertrophic cardiomyopathy v4.21 MT-TI Achchuthan Shanmugasundram Added comment: Comment on list classification: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber.

Below is the summary of recommendation from the NHS Genomic Medicine Service:
MT-TI appears to cause a pretty severe early-onset cardiomyopathy often with other mitochondrial features where reported and therefore suggest that it remains as amber on this panel and is better placed as a green rated gene on R135 where it is already green rated.
Hypertrophic cardiomyopathy v4.21 MT-TI Achchuthan Shanmugasundram Gene: mt-ti has been classified as Amber List (Moderate Evidence).
Hypertrophic cardiomyopathy v4.20 MT-TI Achchuthan Shanmugasundram edited their review of gene: MT-TI: Changed rating: AMBER
Paroxysmal central nervous system disorders v3.13 ALPK1 Achchuthan Shanmugasundram Classified gene: ALPK1 as Red List (low evidence)
Paroxysmal central nervous system disorders v3.13 ALPK1 Achchuthan Shanmugasundram Added comment: Comment on list classification: After NHS Genomic Medicine Service consideration, the rating of this gene has been updated to red. This is based on a red review from Ian Berry.
Paroxysmal central nervous system disorders v3.13 ALPK1 Achchuthan Shanmugasundram Gene: alpk1 has been classified as Red List (Low Evidence).
Congenital myopathy v5.14 VWA1 Arina Puzriakova Deleted their review
Paroxysmal central nervous system disorders v3.12 ALPK1 Achchuthan Shanmugasundram reviewed gene: ALPK1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Paroxysmal central nervous system disorders v3.12 ALPK1 Achchuthan Shanmugasundram Deleted their review
Congenital myopathy v5.14 VWA1 Achchuthan Shanmugasundram Publications for gene: VWA1 were set to 33459760
Congenital myopathy v5.13 VWA1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene should remain amber on this panel based on recommendation by Anna Sarkozy. Her recommendation is based on evidence from new publications on this gene and associated phenotype, which is summarised in the review, PMID:39502942.

The recommendation from the NHS Genomic Medicine Service is as below:
The myopathic nature of the conditions associated with this gene remains controversial and currently there doesn't appear to be sufficient evidence to consider VWA1-related disorder as a myopathy. Therefore this gene-condition is out of scope of this Clinical Indication and at most should remain amber.; to: The rating of this gene should remain amber on this panel based on recommendation by Anna Sarkozy. Her recommendation is based on evidence from new publications on this gene and associated phenotype, which is summarised in the review, PMID:39502942.

The recommendation from the NHS Genomic Medicine Service is as below:
The myopathic nature of the conditions associated with this gene remains controversial and currently there doesn't appear to be sufficient evidence to consider VWA1-related disorder as a myopathy. Therefore this gene-condition is out of scope of this Clinical Indication and at most should remain amber.
Congenital myopathy v5.13 VWA1 Achchuthan Shanmugasundram Classified gene: VWA1 as Amber List (moderate evidence)
Congenital myopathy v5.13 VWA1 Achchuthan Shanmugasundram Added comment: Comment on list classification: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber.
Congenital myopathy v5.13 VWA1 Achchuthan Shanmugasundram Gene: vwa1 has been classified as Amber List (Moderate Evidence).
Congenital myopathy v5.12 VWA1 Achchuthan Shanmugasundram commented on gene: VWA1: The rating of this gene should remain amber on this panel based on recommendation by Anna Sarkozy. Her recommendation is based on evidence from new publications on this gene and associated phenotype, which is summarised in the review, PMID:39502942.

The recommendation from the NHS Genomic Medicine Service is as below:
The myopathic nature of the conditions associated with this gene remains controversial and currently there doesn't appear to be sufficient evidence to consider VWA1-related disorder as a myopathy. Therefore this gene-condition is out of scope of this Clinical Indication and at most should remain amber.
Congenital myopathy v5.12 VWA1 Achchuthan Shanmugasundram reviewed gene: VWA1: Rating: AMBER; Mode of pathogenicity: None; Publications: 39502942; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dilated and arrhythmogenic cardiomyopathy v2.36 TAX1BP3 Riyaad Aungraheeta gene: TAX1BP3 was added
gene: TAX1BP3 was added to Dilated and arrhythmogenic cardiomyopathy. Sources: Literature
Mode of inheritance for gene: TAX1BP3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TAX1BP3 were set to 39963794
Phenotypes for gene: TAX1BP3 were set to Arrhythmogenic cardiomyopathy
Review for gene: TAX1BP3 was set to AMBER
Added comment: Sources: Literature
Intellectual disability v8.87 ZFHX4 Arina Puzriakova Publications for gene: ZFHX4 were set to 26350204; 21802062; 33057194; 24038936
Intellectual disability v8.86 ZFHX4 Arina Puzriakova commented on gene: ZFHX4
Retinal disorders v7.6 SAG Sarah Leigh Publications for gene: SAG were set to
Intellectual disability v8.86 ARHGEF40 Sarah Leigh Classified gene: ARHGEF40 as Amber List (moderate evidence)
Intellectual disability v8.86 ARHGEF40 Sarah Leigh Gene: arhgef40 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.85 ARHGEF40 Sarah Leigh gene: ARHGEF40 was added
gene: ARHGEF40 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: ARHGEF40 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: ARHGEF40 were set to 39838643
Phenotypes for gene: ARHGEF40 were set to developmental delay
Review for gene: ARHGEF40 was set to AMBER
Added comment: Two de novo ARHGEF40 variants have been identified in two individuals with multiple congenital anomalies and developmental delay (PMID: 39838643). The two variants affected the same residue (NM_018071: c.673 C>T, NP_060541: p.Arg225Trp, NM_018071: c.674 G>A, NP_060541: p.Arg225Gln). Both patients had global developmental delay, delayed speech and language development, hypotonia, short stature and impaired hearing.
Sources: Literature
Monogenic hearing loss v4.72 ATP6V1B1 Celia Duff-Farrier reviewed gene: ATP6V1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID 39837581; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal tubulopathies v4.21 ATP6V1B1 Celia Duff-Farrier reviewed gene: ATP6V1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID 39837581; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Nephrocalcinosis or nephrolithiasis v4.19 ATP6V1B1 Celia Duff-Farrier reviewed gene: ATP6V1B1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID 39837581; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Skeletal dysplasia v7.21 DDR2 Sarah Leigh Added comment: Comment on mode of pathogenicity: Monoallelic DDR2 variants associated with Warburg-Cinotti syndrome, (OMIM: 618175), appear to have a gain of function mode of pathogenicity.
Skeletal dysplasia v7.21 DDR2 Sarah Leigh Mode of pathogenicity for gene: DDR2 was changed from to None
Skeletal dysplasia v7.20 DDR2 Sarah Leigh Publications for gene: DDR2 were set to 30449416; 39095787; 23637089; 30449416
Skeletal dysplasia v7.19 DDR2 Sarah Leigh Tag Q1_25_ NHS_review tag was added to gene: DDR2.
Tag Q1_25_ MOI tag was added to gene: DDR2.
Skeletal dysplasia v7.19 DDR2 Sarah Leigh Phenotypes for gene: DDR2 were changed from Spondylometaepiphyseal dysplasia, short limb-hand type 271665, at least 3 cases reported; Spondylometaepiphyseal dysplasia, short limb-hand type 271665 to Spondylometaepiphyseal dysplasia, short limb-hand type 271665, at least 3 cases reported; Spondylometaepiphyseal dysplasia, short limb-hand type 271665; Warburg-Cinotti syndrome, OMIM: 618175
Skeletal dysplasia v7.18 DDR2 Sarah Leigh Publications for gene: DDR2 were set to 30449416; 39095787
Skeletal dysplasia v7.17 DDR2 Sarah Leigh edited their review of gene: DDR2: Added comment: A change of mode of inheritance from biallelic to BOTH monoallelic and biallelic is requested, so that monoallelic DDR2 variants causing Warburg-Cinotti syndrome (OMIM: 618175) may be detected. Warburg-Cinotti syndrome includes skeletal dysplasia features (PMID: 23637089; 30449416). Functional studies of the two variants so far associated with Warburg-Cinotti syndrome, appear to have a gain of function mechanism. Cultured fibroblasts from the patients resulted in increased phosphorylation of DDR2 in comparison to the control fibroblasts, thereby causing autophosphorylation of the receptor (PMID: 30449416).; Changed publications to: 23637089, 30449416; Changed phenotypes to: Warburg-Cinotti syndrome, OMIM: 618175; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic short stature v1.1 GH1 Melissa Connolly reviewed gene: GH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Growth hormone deficiency, Kowarski syndrome; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Monogenic short stature v1.1 RNPC3 Melissa Connolly reviewed gene: RNPC3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Pituitary hormone deficiency, combined or isolated, 7; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.84 AFF3_GCC Eleanor Williams commented on STR: AFF3_GCC
Paroxysmal central nervous system disorders v3.12 ALPK1 Ian Berry reviewed gene: ALPK1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v8.84 SLC5A7 Arina Puzriakova Publications for gene: SLC5A7 were set to 30914295; 27569547; 39135055
Intellectual disability v8.83 SLC5A7 Arina Puzriakova Tag watchlist was removed from gene: SLC5A7.
Tag Q1_25_ promote_green tag was added to gene: SLC5A7.
Intellectual disability v8.83 SLC5A7 Arina Puzriakova edited their review of gene: SLC5A7: Changed rating: GREEN; Changed publications to: 27569547, 39135055, 36840359, 36611016, 33250374; Changed phenotypes to: Myasthenic syndrome, congenital, 20, presynaptic, OMIM:617143; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.83 SLC5A7 Arina Puzriakova commented on gene: SLC5A7: Some patients with SLC5A7-related CMS can exhibit developmental delay and cognitive impairment (PMID: 27569547; 39135055; 36840359; 36611016; 33250374). Although this feature is not universal, there are sufficient unrelated cases where cognitive deficit is an defining feature of the early phenotype, to warrant inclusion of SLC5A7 on this panel.
Intellectual disability v8.83 SLC5A7 Arina Puzriakova Phenotypes for gene: SLC5A7 were changed from Myasthenic syndrome, congenital, 20, presynaptic,CMS20, 617143 to Myasthenic syndrome, congenital, 20, presynaptic, OMIM:617143
Intellectual disability v8.82 SLC5A7 Arina Puzriakova Mode of inheritance for gene: SLC5A7 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.81 SLC5A7 Arina Puzriakova Added comment: Comment on publications: PMID:39135055 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques
Intellectual disability v8.81 SLC5A7 Arina Puzriakova Publications for gene: SLC5A7 were set to 30914295; 27569547
Early onset or syndromic epilepsy v7.31 TRPM7 Sarah Leigh Classified gene: TRPM7 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v7.31 TRPM7 Sarah Leigh Gene: trpm7 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v7.11 TRPM7 Sarah Leigh Classified gene: TRPM7 as Amber List (moderate evidence)
Likely inborn error of metabolism v7.11 TRPM7 Sarah Leigh Gene: trpm7 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v7.30 TRPM7 Sarah Leigh gene: TRPM7 was added
gene: TRPM7 was added to Early onset or syndromic epilepsy. Sources: Literature
Q1_23_promote_green tags were added to gene: TRPM7.
Mode of inheritance for gene: TRPM7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TRPM7 were set to 39099563; 35712613; 35561741
Phenotypes for gene: TRPM7 were set to hypomagnesaemia with secondary hypocalcaemia
Review for gene: TRPM7 was set to GREEN
Added comment: Heterozygous TRPM7 variants are associated with hypomagnesaemia with secondary hypocalcaemia (HSH)(PMID: 39099563; 35712613; 35561741). Six TRPM7 variants have been identified in six unrelated cases of HSH, one of the variants was found in three members of one family. The remaining variants were de novo. In addition to HSH, other phenotypic feature have been seen in those carrying TRPM7 variants, including seizures (4/6), motor skill defects (5/6), autism spectrum disorder (4/6) (PMID: 39099563; 35712613; 35561741). Functional studies suggest a loss of function effect of the TRPM7 variants (PMID: 39099563; 35561741).
Sources: Literature
Likely inborn error of metabolism v7.10 TRPM7 Sarah Leigh gene: TRPM7 was added
gene: TRPM7 was added to Likely inborn error of metabolism. Sources: Literature
Q1_23_promote_green tags were added to gene: TRPM7.
Mode of inheritance for gene: TRPM7 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: TRPM7 were set to 39099563; 35712613; 35561741
Phenotypes for gene: TRPM7 were set to hypomagnesaemia with secondary hypocalcaemia
Review for gene: TRPM7 was set to GREEN
Added comment: Heterozygous TRPM7 variants are associated with hypomagnesaemia with secondary hypocalcaemia (HSH)(PMID: 39099563; 35712613; 35561741). Six TRPM7 variants have been identified in six unrelated cases of HSH, one of the variants was found in three members of one family. The remaining variants were de novo. In addition to HSH, other phenotypic feature have been seen in those carrying TRPM7 variants, including seizures (4/6), motor skill defects (5/6), autism spectrum disorder (4/6) (PMID: 39099563; 35712613; 35561741). Functional studies suggest a loss of function effect of the TRPM7 variants (PMID: 39099563; 35561741).
Sources: Literature
Paediatric or syndromic cardiomyopathy v6.5 ASNA1 Dmitrijs Rots gene: ASNA1 was added
gene: ASNA1 was added to Paediatric or syndromic cardiomyopathy. Sources: Literature
Mode of inheritance for gene: ASNA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASNA1 were set to PMID: 31461301
Phenotypes for gene: ASNA1 were set to Rapidly Progressive Pediatric Cardiomyopathy
Review for gene: ASNA1 was set to AMBER
Added comment: 3 families with functional evidence described in PMID: 31461301
Sources: Literature
Paediatric or syndromic cardiomyopathy v6.5 FLII Dmitrijs Rots reviewed gene: FLII: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 37561591; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hypertrophic cardiomyopathy v4.20 ALPK3 Dmitrijs Rots commented on gene: ALPK3: As mentioned - should be BOTH biallelic and monoallelic. Still not updated.
Monogenic hearing loss v4.72 MT-CO1 Sarah Leigh commented on gene: MT-CO1: There are numerous reports of mtDNA heteroplasmy associated with mitochondrial non-syndromic sensorineural hearing loss (OMIM: 500008), involving MT-CO1 variant rs199474822, and other variants, including the MT-RNR1 variant rs267606617 (PMID: 26328603; 29605341; 32169613).
Monogenic hearing loss v4.72 MT-CO1 Sarah Leigh Classified gene: MT-CO1 as Amber List (moderate evidence)
Monogenic hearing loss v4.72 MT-CO1 Sarah Leigh Gene: mt-co1 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.71 MT-CO1 Sarah Leigh gene: MT-CO1 was added
gene: MT-CO1 was added to Monogenic hearing loss. Sources: Literature
Q1_25_ NHS_review, Q1_25_ promote_green tags were added to gene: MT-CO1.
Mode of inheritance for gene gene: MT-CO1 was set to MITOCHONDRIAL
Publications for gene: MT-CO1 were set to 10577941; 16152638; 9832034; 30035268; 26328603; 29605341; 32169613
Phenotypes for gene: MT-CO1 were set to Deafness, non-syndromic sensorineural, mitochondrial, OMIM: 500008; mitochondrial non-syndromic sensorineural hearing loss, MONDO:0010779
Review for gene: MT-CO1 was set to GREEN
Added comment: Sources: Literature
Retinal disorders v7.5 SPG11 Siying Lin gene: SPG11 was added
gene: SPG11 was added to Retinal disorders. Sources: Literature
Mode of inheritance for gene: SPG11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPG11 were set to PMID: 19194956, 36343909, 38613257,21035867
Phenotypes for gene: SPG11 were set to Retinal dystrophy; spastic paraplegia
Mode of pathogenicity for gene: SPG11 was set to Other
Review for gene: SPG11 was set to GREEN
Added comment: Kjellin syndrome is a form of complex hereditary spastic paraplegia, associated with 2 genes, SPG11 and SPG15/ZFYVE26. Patients have a consistent retinal phenotype with flecked maculopathy and associated autofluorescence changes. ZFYVE26 is already listed as a green gene on the retinal panel.
Sources: Literature
Intellectual disability v8.80 INPP4A Eleanor Williams Tag Q1_25_ promote_green tag was added to gene: INPP4A.
Intellectual disability v8.80 INPP4A Eleanor Williams changed review comment from: More information about previously reported cases and additional cases:

PMID: 21937992 Najmabadi et al 2011 - Report 3 related Iranian probands with moderate intellectual disability and a homozyous 1 bp deletion leading to a frameshift variant in INPP4A:D915fs. No detailed phenotype information, although stated as non-syndromic.

PMIDs: 25338135 - Sheffer et al 2015 - child from healthy consanguineous Arab Moslem parents, found to have hindbrain malformations at 4 months of age. No eye blinking in response to light. Started to have myoclonic seizures at 8 months. The patient had no developmental milestones and was cortically blind. At 15 months, head circumference was 39.5 cm (<3 SD for age). A homozygous frame-shift mutation c.1581 del256, p.Glu528Ilefs*22 in exon 15 of INPP4A was found. It segregated within the family.

PMID: 31978615 - Banihashemi et al 2020 - 5 individuals with severe intellectual disability from an extended Arab Iranian family and patients were born from consanguineous marriages. Patients presented at ages 2-4 years. Brain MRIs were normal. However, EEGs was abnormal due to the presence of generalized slowing waves with no epileptiform discharge. Only IV-2 had myoclonic seizures during infancy. A homozygous nonsense variant INPP4A c.115 C > T; p.Gln39X variant was identified, which segregated with the phenotype in the family (9 unaffected members were either heterozygous or wild type homozygous).

PMID: 36653678 - Hecher et al 2023 - 2-year-old girl whose parents were a healthy consanguineous Turkish couple with microcephaly (OFC of 27.5 cm (− 2.88 z) at birth), severe developmental delay, myoclonic seizures, and pontocerebellar hypoplasia, carrying the novel homozygous INPP4A frameshift variant c.2840del/p.(Gly947Glufs*12) (NM_001134224.2).

There are now 4 families in which homozygous variants in INPP4A are reported in probands with severe intellectual disability. Myoclonic seizures are reported in some patients from an early age, but this is alongside brain abnormalities in 2 cases, suggesting that the seizures are not the only cause for the intellectual disability.; to: More information about previously reported cases and additional cases:

PMID: 21937992 Najmabadi et al 2011 - Report 3 related Iranian probands with moderate intellectual disability and a homozyous 1 bp deletion leading to a frameshift variant in INPP4A:D915fs. No detailed phenotype information, although stated as non-syndromic.

PMIDs: 25338135 - Sheffer et al 2015 - child from healthy consanguineous Arab Moslem parents, found to have hindbrain malformations at 4 months of age. No eye blinking in response to light. Started to have myoclonic seizures at 8 months. The patient had no developmental milestones and was cortically blind. At 15 months, head circumference was 39.5 cm (<3 SD for age). A homozygous frame-shift mutation c.1581 del256, p.Glu528Ilefs*22 in exon 15 of INPP4A was found. It segregated within the family.

PMID: 31978615 - Banihashemi et al 2020 - 5 individuals with severe intellectual disability from an extended Arab Iranian family and patients were born from consanguineous marriages. Patients presented at ages 2-4 years. Brain MRIs were normal. However, EEGs was abnormal due to the presence of generalized slowing waves with no epileptiform discharge. Only IV-2 had myoclonic seizures during infancy. A homozygous nonsense variant INPP4A c.115 C > T; p.Gln39X variant was identified, which segregated with the phenotype in the family (9 unaffected members were either heterozygous or wild type homozygous).

PMID: 36653678 - Hecher et al 2023 - 2-year-old girl whose parents were a healthy consanguineous Turkish couple with microcephaly (OFC of 27.5 cm (− 2.88 z) at birth), severe developmental delay, myoclonic seizures, and pontocerebellar hypoplasia, carrying the novel homozygous INPP4A frameshift variant c.2840del/p.(Gly947Glufs*12) (NM_001134224.2).

There are now 4 families in which homozygous variants in INPP4A are reported in probands with severe intellectual disability. Myoclonic seizures are reported in some patients from an early age, but this is alongside brain abnormalities in 2 cases, suggesting that the seizures are not the only cause for the intellectual disability.

See also review by Medyanik et al 2025 PMID: 39858526.
Intellectual disability v8.80 INPP4A Eleanor Williams Publications for gene: INPP4A were set to 21937992; 31978615; 31938306; 25338135; 20011524
Intellectual disability v8.79 INPP4A Eleanor Williams Classified gene: INPP4A as Amber List (moderate evidence)
Intellectual disability v8.79 INPP4A Eleanor Williams Added comment: Comment on list classification: Leaving as amber, but with a recommendation to promote to green following GMS approval.
Intellectual disability v8.79 INPP4A Eleanor Williams Gene: inpp4a has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.78 INPP4A Eleanor Williams commented on gene: INPP4A
Ataxia and cerebellar anomalies - narrow panel v7.16 FTH1 Sarah Leigh Tag Q4_24_promote_green was removed from gene: FTH1.
Tag Q1_25_ NHS_review tag was added to gene: FTH1.
Tag Q1_25_ promote_green tag was added to gene: FTH1.
Iron metabolism disorders - NOT common HFE mutations v2.12 FTH1 Sarah Leigh Tag Q4_24_promote_green was removed from gene: FTH1.
Iron metabolism disorders - NOT common HFE mutations v2.12 FTH1 Sarah Leigh edited their review of gene: FTH1: Changed rating: AMBER
Iron metabolism disorders - NOT common HFE mutations v2.12 FTH1 Sarah Leigh changed review comment from: Three monoallelic terminating FTH1 variants (NM_002032: c.487_490 dupGAAT, (p.Ser164*), c.512_513delTT, (p.Phe171*), c.409_410del; p.H137fs*) have been associated with Neurodegeneration with brain iron accumulation 9 (OMIM: 620669)(PMID:37660254; 37265023) in six unrelated cases. Shieh et al (PMID:37660254), report patient fibroblasts studies, which indicate that variants c.487_490 dupGAAT and c.512_513delTT escape nonsense-mediated mRNA decay, resulting in a C-terminally truncated protein, which is predicted to have a dominant-negative effect. Molecular modeling predicts that this could reduce the iron-storage capacity, resulting in iron accumulation. Shieh et al go onto demonstrate that the targeted knockdown of the S164* FTH1 transcript, with antisense oligonucleotides in vitro partially rescued the abnormal cellular phenotype.; to: Three monoallelic terminating FTH1 variants (NM_002032: c.487_490 dupGAAT, (p.Ser164*), c.512_513delTT, (p.Phe171*), c.409_410del; p.H137fs*) have been associated with Neurodegeneration with brain iron accumulation 9 (OMIM: 620669)(PMID:37660254; 37265023) in six unrelated cases. Shieh et al (PMID:37660254), report patient fibroblasts studies, which indicate that variants c.487_490 dupGAAT and c.512_513delTT escape nonsense-mediated mRNA decay, resulting in a C-terminally truncated protein, which is predicted to have a dominant-negative effect. Molecular modeling predicts that this could reduce the iron-storage capacity, resulting in iron accumulation. Shieh et al go onto demonstrate that the targeted knockdown of the S164* FTH1 transcript, with antisense oligonucleotides in vitro partially rescued the abnormal cellular phenotype.
Table 1 in PMID: 37660254, shows that although FTH1 is an iron metabolism gene, the phenotype in the patients appears to include normal ferritin and iron measurements, except the accumulation in tissues such as the brain.
Ataxia and cerebellar anomalies - narrow panel v7.16 FTH1 Sarah Leigh Entity copied from Iron metabolism disorders - NOT common HFE mutations v2.12
Ataxia and cerebellar anomalies - narrow panel v7.16 FTH1 Sarah Leigh gene: FTH1 was added
gene: FTH1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: North West GLH,NHS GMS,Expert Review Amber,Yorkshire and North East GLH,London South GLH,Wessex and West Midlands GLH
Q4_24_promote_green tags were added to gene: FTH1.
Mode of inheritance for gene: FTH1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FTH1 were set to 11389486; 37660254; 37265023
Phenotypes for gene: FTH1 were set to Neurodegeneration with brain iron accumulation 9, OMIM:620669; ?Hemochromatosis, type 5 OMIM:615517; hemochromatosis type 5 MONDO:0014225
Fetal anomalies v5.12 EMG1 Achchuthan Shanmugasundram Phenotypes for gene: EMG1 were changed from Bowen-Conradi syndrome; Bowen-Conradi syndrome, 211180 to Bowen-Conradi syndrome, OMIM:211180
Skeletal dysplasia v7.17 DDR2 Sarah Leigh Publications for gene: DDR2 were set to
Fetal anomalies v5.11 ABCD4 Achchuthan Shanmugasundram Phenotypes for gene: ABCD4 were changed from METHYLMALONIC ACIDURIA AND HOMOCYSTINURIA, CBLJ TYPE to Methylmalonic aciduria and homocystinuria, cblJ type, OMIM:614857
Intellectual disability v8.78 PTRH2 Achchuthan Shanmugasundram Classified gene: PTRH2 as Amber List (moderate evidence)
Intellectual disability v8.78 PTRH2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of biallelic PTRH2 variants with intellectual disability/ global developmental delay. Hence, this gene can be promoted to green rating in the next GMS update.
Intellectual disability v8.78 PTRH2 Achchuthan Shanmugasundram Gene: ptrh2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.77 PTRH2 Achchuthan Shanmugasundram Phenotypes for gene: PTRH2 were changed from Infantile-onset multisystem neurologic, endocrine, and pancreatic disease, 616263; Infantile-onset multisystem neurologic, endocrine, and pancreatic disease (MIM 616263) to Infantile-onset multisystem neurologic, endocrine, and pancreatic disease, OMIM:616263
Intellectual disability v8.76 PTRH2 Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: PTRH2.
Intellectual disability v8.76 PTRH2 Achchuthan Shanmugasundram edited their review of gene: PTRH2: Changed phenotypes to: Infantile-onset multisystem neurologic, endocrine, and pancreatic disease, OMIM:616263
Intellectual disability v8.76 PTRH2 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39176129 and PMID:39766776 papers were identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.76 PTRH2 Achchuthan Shanmugasundram Publications for gene: PTRH2 were set to 25574476; 28175314; 28328138; 25558065; 27129381
Intellectual disability v8.75 PTRH2 Achchuthan Shanmugasundram reviewed gene: PTRH2: Rating: GREEN; Mode of pathogenicity: None; Publications: 39176129, 39766776; Phenotypes: infantile-onset multisystem neurologic, endocrine, and pancreatic disease, OMIM:616263; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.75 RUNX1T1 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39568205 paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.75 RUNX1T1 Achchuthan Shanmugasundram Publications for gene: RUNX1T1 were set to 22644616; 39568205
Intellectual disability v8.74 RUNX1T1 Achchuthan Shanmugasundram Classified gene: RUNX1T1 as Amber List (moderate evidence)
Intellectual disability v8.74 RUNX1T1 Achchuthan Shanmugasundram Gene: runx1t1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.73 RUNX1T1 Achchuthan Shanmugasundram gene: RUNX1T1 was added
gene: RUNX1T1 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: RUNX1T1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RUNX1T1 were set to 22644616; 39568205
Phenotypes for gene: RUNX1T1 were set to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: RUNX1T1 was set to AMBER
Added comment: PMID:22644616 reported a patient with mild intellectual disability and de novo deletion within the RUNX1T1 gene.

PMID:39568205 reported three unrelated individuals with neurodevelopmental and congenital anomalies and with de novo variants in RUNX1T1 gene. Although delayed speech and language development and delayed fine motor development was reported in all three cases, global developmental delay was only reported in two of them.

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.

Hence, this gene should be rated amber with current evidence.
Sources: Literature
Intellectual disability v8.72 NFIB Achchuthan Shanmugasundram Classified gene: NFIB as Amber List (moderate evidence)
Intellectual disability v8.72 NFIB Achchuthan Shanmugasundram Added comment: Comment on list classification: The patients reported in PMID:30388402 presented with borderline-mild intellectual disability. The severity of ID/ GDD was not reported for the single patient with NFIB variant from PMID:39567597. Hence, the rating should still remain amber with current evidence.
Intellectual disability v8.72 NFIB Achchuthan Shanmugasundram Gene: nfib has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.71 NFIB Achchuthan Shanmugasundram changed review comment from: Comment on publications: PMID:9567597 paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.; to: Comment on publications: PMID:39567597 paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.71 NFIB Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:9567597 paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.71 NFIB Achchuthan Shanmugasundram Publications for gene: NFIB were set to 30388402; 39567597
Intellectual disability v8.70 NFIB Achchuthan Shanmugasundram Phenotypes for gene: NFIB were changed from Global developmental delay; Intellectual disability; Macrocephaly; Macrocephaly, acquired, with impaired intellectual development, 618286 to Macrocephaly, acquired, with impaired intellectual development, OMIM:618286
Intellectual disability v8.69 NFIB Achchuthan Shanmugasundram Publications for gene: NFIB were set to 30388402
Intellectual disability v8.68 NFIB Achchuthan Shanmugasundram Mode of inheritance for gene: NFIB was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v8.67 NFIB Achchuthan Shanmugasundram reviewed gene: NFIB: Rating: AMBER; Mode of pathogenicity: None; Publications: 39567597; Phenotypes: Macrocephaly, acquired, with impaired intellectual development, OMIM:618286; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v7.5 GPATCH11 Achchuthan Shanmugasundram Classified gene: GPATCH11 as Amber List (moderate evidence)
Retinal disorders v7.5 GPATCH11 Achchuthan Shanmugasundram Gene: gpatch11 has been classified as Amber List (Moderate Evidence).
Retinal disorders v7.4 GPATCH11 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39572588 paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Retinal disorders v7.4 GPATCH11 Achchuthan Shanmugasundram Publications for gene: GPATCH11 were set to 39572588
Retinal disorders v7.3 GPATCH11 Achchuthan Shanmugasundram Phenotypes for gene: GPATCH11 were changed from neuronevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; retinal disorder, MONDO:0005283
Retinal disorders v7.2 GPATCH11 Achchuthan Shanmugasundram changed review comment from: PMID:39572588 reported 12 individuals from six unrelated families presenting with a syndromic disease and they were identified with biallelic variants in GPATCH11 gene. Intellectual disability was present in three unrelated families, while global developmental delay was reported in all.

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature; to: PMID:39572588 reported 12 individuals from six unrelated families presenting with a syndromic disease and they were identified with biallelic variants in GPATCH11 gene. Retinal dystrophy and mild foveolar hypoplasia were reported in one family, whereas macular atrophy was reported in a different family. Signs of retinitis pigmentosa was reported in another family.

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Retinal disorders v7.2 GPATCH11 Achchuthan Shanmugasundram edited their review of gene: GPATCH11: Changed rating: AMBER; Changed phenotypes to: neurodevelopmental disorder, MONDO:0700092, retinal disorder, MONDO:0005283
Intellectual disability v8.67 GPATCH11 Achchuthan Shanmugasundram Phenotypes for gene: GPATCH11 were changed from neuronevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v8.66 GPATCH11 Achchuthan Shanmugasundram edited their review of gene: GPATCH11: Changed phenotypes to: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071
Intellectual disability v8.66 GPATCH11 Achchuthan Shanmugasundram Classified gene: GPATCH11 as Amber List (moderate evidence)
Intellectual disability v8.66 GPATCH11 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Intellectual disability v8.66 GPATCH11 Achchuthan Shanmugasundram Gene: gpatch11 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.65 GPATCH11 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39572588 paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.65 GPATCH11 Achchuthan Shanmugasundram Publications for gene: GPATCH11 were set to 39572588
Intellectual disability v8.64 GPATCH11 Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: GPATCH11.
Retinal disorders v7.2 GPATCH11 Achchuthan Shanmugasundram gene: GPATCH11 was added
gene: GPATCH11 was added to Retinal disorders. Sources: Literature
Mode of inheritance for gene: GPATCH11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPATCH11 were set to 39572588
Phenotypes for gene: GPATCH11 were set to neuronevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: GPATCH11 was set to GREEN
Added comment: PMID:39572588 reported 12 individuals from six unrelated families presenting with a syndromic disease and they were identified with biallelic variants in GPATCH11 gene. Intellectual disability was present in three unrelated families, while global developmental delay was reported in all.

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v8.64 GPATCH11 Achchuthan Shanmugasundram gene: GPATCH11 was added
gene: GPATCH11 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: GPATCH11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GPATCH11 were set to 39572588
Phenotypes for gene: GPATCH11 were set to neuronevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: GPATCH11 was set to GREEN
Added comment: PMID:39572588 reported 12 individuals from six unrelated families presenting with a syndromic disease and they were identified with biallelic variants in GPATCH11 gene. Intellectual disability was present in three unrelated families, while global developmental delay was reported in all.

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Early onset or syndromic epilepsy v7.29 GLS Achchuthan Shanmugasundram Classified gene: GLS as Amber List (moderate evidence)
Early onset or syndromic epilepsy v7.29 GLS Achchuthan Shanmugasundram Added comment: Comment on list classification: There are three unrelated cases reported with biallelic GLS variants and with epilepsy. Hence, this gene can be promoted to green rating in the next GMS update.
Early onset or syndromic epilepsy v7.29 GLS Achchuthan Shanmugasundram Gene: gls has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v7.28 GLS Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: GLS.
Early onset or syndromic epilepsy v7.28 GLS Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39559284 paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Early onset or syndromic epilepsy v7.28 GLS Achchuthan Shanmugasundram Publications for gene: GLS were set to 30575854
Early onset or syndromic epilepsy v7.27 GLS Achchuthan Shanmugasundram reviewed gene: GLS: Rating: GREEN; Mode of pathogenicity: None; Publications: 39559284; Phenotypes: Developmental and epileptic encephalopathy 71, OMIM:618328; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v4.70 LHX3 Achchuthan Shanmugasundram Classified gene: LHX3 as Amber List (moderate evidence)
Monogenic hearing loss v4.70 LHX3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Monogenic hearing loss v4.70 LHX3 Achchuthan Shanmugasundram Gene: lhx3 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.69 LHX3 Achchuthan Shanmugasundram Mode of inheritance for gene: LHX3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v4.68 LHX3 Achchuthan Shanmugasundram Phenotypes for gene: LHX3 were changed from to Pituitary hormone deficiency, combined, 3, OMIM:221750; sensorineural hearing loss disorder, MONDO:0020678
Monogenic hearing loss v4.67 LHX3 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39548529 paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Monogenic hearing loss v4.67 LHX3 Achchuthan Shanmugasundram Publications for gene: LHX3 were set to
Monogenic hearing loss v4.66 LHX3 Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: LHX3.
Monogenic hearing loss v4.66 LHX3 Achchuthan Shanmugasundram changed review comment from: PMID:10835633 reported two unrelated families with combined pituitary hormone deficiency and with biallelic LHX3 variants. The three patients from a family identified with p.Tyr116Cys variant had mild-moderate bilateral sensorineural hearing loss, while the patient with 23bp deletion had profound sensorineural deafness, when re-investigated in PMID:18407919.

PMID:18407919 reported two families with novel recessive variants in LHX3 gene. They all exhibited varying degrees of bilateral sensorineural hearing loss.

PMID:39548529 reported a group of eight patients with combined pituitary hormone deficiency-3 and all of them were identified with the same homozygous variant, c.455-2A > G. They presented with progressive sensorineural hearing deficiency ranging from moderately severe to complete loss. This variant was also associated with vestibular impairment.; to: PMID:10835633 reported two unrelated families with combined pituitary hormone deficiency and with biallelic LHX3 variants. The three patients from a family identified with p.Tyr116Cys variant had mild-moderate bilateral sensorineural hearing loss, while the patient with 23bp deletion had profound sensorineural deafness, when re-investigated in PMID:18407919.

PMID:18407919 reported two families with novel recessive variants in LHX3 gene. They all exhibited varying degrees of bilateral sensorineural hearing loss.

PMID:39548529 reported a group of eight patients with combined pituitary hormone deficiency-3 and all of them were identified with the same homozygous variant, c.455-2A > G. They presented with progressive sensorineural hearing deficiency ranging from moderately severe to complete loss. This variant is present as a founder variant in the population in Northern Sweden and was also associated with vestibular impairment.
Monogenic hearing loss v4.66 LHX3 Achchuthan Shanmugasundram reviewed gene: LHX3: Rating: GREEN; Mode of pathogenicity: None; Publications: 10835633, 18407919, 39548529; Phenotypes: Pituitary hormone deficiency, combined, 3, OMIM:221750, sensorineural hearing loss disorder, MONDO:0020678; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v7.1 DHX38 Cassandra Smith reviewed gene: DHX38: Rating: AMBER; Mode of pathogenicity: None; Publications: 24737827, 30208423, 37867960; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.10 ITGAV Achchuthan Shanmugasundram Classified gene: ITGAV as Amber List (moderate evidence)
Fetal anomalies v5.10 ITGAV Achchuthan Shanmugasundram Added comment: Comment on list classification: There are four foetuses from a single family and functional data reported. Hence, this gene can be rated amber with current evidence.
Fetal anomalies v5.10 ITGAV Achchuthan Shanmugasundram Gene: itgav has been classified as Amber List (Moderate Evidence).
Fetal anomalies v5.9 ITGAV Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39526957 paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Fetal anomalies v5.9 ITGAV Achchuthan Shanmugasundram Publications for gene: ITGAV were set to 39526957
Primary immunodeficiency or monogenic inflammatory bowel disease v7.24 ITGAV Achchuthan Shanmugasundram Classified gene: ITGAV as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v7.24 ITGAV Achchuthan Shanmugasundram Added comment: Comment on list classification: Two unrelated cases were reported with inflammatory bowel disease, immune dysregulation and recurrent infections. Hence, this gene can be rated amber with current evidence.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.24 ITGAV Achchuthan Shanmugasundram Gene: itgav has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v7.23 ITGAV Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39526957 paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.23 ITGAV Achchuthan Shanmugasundram Publications for gene: ITGAV were set to 39526957
Intellectual disability v8.63 ITGAV Achchuthan Shanmugasundram Classified gene: ITGAV as Amber List (moderate evidence)
Intellectual disability v8.63 ITGAV Achchuthan Shanmugasundram Added comment: Comment on list classification: As there are two unrelated cases reported with global developmental delay, this gene can be rated amber with current evidence.
Intellectual disability v8.63 ITGAV Achchuthan Shanmugasundram Gene: itgav has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.62 ITGAV Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39526957 paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.62 ITGAV Achchuthan Shanmugasundram Publications for gene: ITGAV were set to 39526957
Fetal anomalies v5.8 ITGAV Achchuthan Shanmugasundram gene: ITGAV was added
gene: ITGAV was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ITGAV was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITGAV were set to 39526957
Phenotypes for gene: ITGAV were set to syndromic disease, MONDO:0002254
Review for gene: ITGAV was set to AMBER
Added comment: PMID:39526957 reported the identification of biallelic ITGAV variants in two unrelated patients and four foetuses from a third family. The two patients were reported with complex phenotype including global developmental delay, eye and brain abnormalities, inflammatory bowel disease and immune dysregulation. The four foetuses were reported with brain and skull abnormalities. There is also functional evidence in support of the association.

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v7.22 ITGAV Achchuthan Shanmugasundram gene: ITGAV was added
gene: ITGAV was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: ITGAV was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITGAV were set to 39526957
Phenotypes for gene: ITGAV were set to syndromic disease, MONDO:0002254
Review for gene: ITGAV was set to AMBER
Added comment: PMID:39526957 reported the identification of biallelic ITGAV variants in two unrelated patients and four foetuses from a third family. The two patients were reported with complex phenotype including global developmental delay, eye and brain abnormalities, inflammatory bowel disease and immune dysregulation. The four foetuses were reported with brain and skull abnormalities. There is also functional evidence in support of the association.

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v8.61 ITGAV Achchuthan Shanmugasundram gene: ITGAV was added
gene: ITGAV was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: ITGAV was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITGAV were set to 39526957
Phenotypes for gene: ITGAV were set to syndromic disease, MONDO:0002254
Review for gene: ITGAV was set to AMBER
Added comment: PMID:39526957 reported the identification of biallelic ITGAV variants in two unrelated patients and four foetuses from a third family. The two patients were reported with complex phenotype including global developmental delay, eye and brain abnormalities, inflammatory bowel disease and immune dysregulation. The four foetuses were reported with brain and skull abnormalities. There is also functional evidence in support of the association.

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v8.60 NAA20 Achchuthan Shanmugasundram Classified gene: NAA20 as Amber List (moderate evidence)
Intellectual disability v8.60 NAA20 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (three unrelated families) for the promotion of this gene to green rating on the next GMS update.
Intellectual disability v8.60 NAA20 Achchuthan Shanmugasundram Gene: naa20 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.59 NAA20 Achchuthan Shanmugasundram Phenotypes for gene: NAA20 were changed from autosomal recessive developmental delay, intellectual disability, and microcephaly to Intellectual developmental disorder, autosomal recessive 73, OMIM:619717
Intellectual disability v8.58 NAA20 Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: NAA20.
Intellectual disability v8.58 NAA20 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39814713 paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.58 NAA20 Achchuthan Shanmugasundram Publications for gene: NAA20 were set to 34230638
Intellectual disability v8.57 NAA20 Achchuthan Shanmugasundram reviewed gene: NAA20: Rating: GREEN; Mode of pathogenicity: None; Publications: 37191084, 39814713; Phenotypes: Intellectual developmental disorder, autosomal recessive 73, OMIM:619717; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v7.27 EEFSEC Achchuthan Shanmugasundram changed review comment from: PMID:39753114 reported nine different individuals from eight unrelated families with a selenopathy with early-onset neurodegeneration. Thy were all identified with six different biallelic variants in EEFSEC gene, of which seven families had variants in homozygous state, while one family had variants in compound heterozygous state. They presented with global developmental delay, moderate or severe cognitive impairment, progressive spasticity, ataxia, and seizures. In addition, cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy. Seizures were reported in seven patients from six families.

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature; to: PMID:39753114 reported nine different individuals from eight unrelated families with a selenopathy with early-onset neurodegeneration. Thy were all identified with six different biallelic variants in EEFSEC gene, of which seven families had variants in homozygous state, while one family had variants in compound heterozygous state. They presented with global developmental delay, moderate or severe cognitive impairment, progressive spasticity, ataxia, and seizures. In addition, cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy. Seizures were reported in seven patients from six families.

In line with the clinical phenotype, an eEFSec-RNAi Drosophila model displays progressive impairment of motor function, which is reflected in the synaptic defects in this model organisms.

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v8.57 EEFSEC Achchuthan Shanmugasundram changed review comment from: PMID:39753114 reported nine different individuals from eight unrelated families with a selenopathy with early-onset neurodegeneration. Thy were all identified with six different biallelic variants in EEFSEC gene, of which seven families had variants in homozygous state, while one family had variants in compound heterozygous state. They presented with global developmental delay, moderate or severe cognitive impairment, progressive spasticity, ataxia, and seizures. In addition, cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy.

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature; to: PMID:39753114 reported nine different individuals from eight unrelated families with a selenopathy with early-onset neurodegeneration. Thy were all identified with six different biallelic variants in EEFSEC gene, of which seven families had variants in homozygous state, while one family had variants in compound heterozygous state. They presented with global developmental delay, moderate or severe cognitive impairment, progressive spasticity, ataxia, and seizures. In addition, cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy.

In line with the clinical phenotype, an eEFSec-RNAi Drosophila model displays progressive impairment of motor function, which is reflected in the synaptic defects in this model organisms.

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v7.15 EEFSEC Achchuthan Shanmugasundram changed review comment from: PMID:39753114 reported nine different individuals from eight unrelated families with a selenopathy with early-onset neurodegeneration. Thy were all identified with six different biallelic variants in EEFSEC gene, of which seven families had variants in homozygous state, while one family had variants in compound heterozygous state. They presented with global developmental delay, moderate or severe cognitive impairment, progressive spasticity, ataxia, and seizures. In addition, cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy. Ataxia was reported in four unrelated cases, cerebellar hypoplasia in one and cerebellar atrophy in four cases from three families.

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature; to: PMID:39753114 reported nine different individuals from eight unrelated families with a selenopathy with early-onset neurodegeneration. Thy were all identified with six different biallelic variants in EEFSEC gene, of which seven families had variants in homozygous state, while one family had variants in compound heterozygous state. They presented with global developmental delay, moderate or severe cognitive impairment, progressive spasticity, ataxia, and seizures. In addition, cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy. Ataxia was reported in four unrelated cases, cerebellar hypoplasia in one and cerebellar atrophy in four cases from three families.

In line with the clinical phenotype, an eEFSec-RNAi Drosophila model displays progressive impairment of motor function, which is reflected in the synaptic defects in this model organisms.

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v7.15 EEFSEC Achchuthan Shanmugasundram Classified gene: EEFSEC as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v7.15 EEFSEC Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.
Ataxia and cerebellar anomalies - narrow panel v7.15 EEFSEC Achchuthan Shanmugasundram Gene: eefsec has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v7.14 EEFSEC Achchuthan Shanmugasundram changed review comment from: PMID:39753114 reported nine different individuals from eight unrelated families with a selenopathy with early-onset neurodegeneration. Thy were all identified with six different biallelic variants in EEFSEC gene, of which seven families had variants in homozygous state, while one family had variants in compound heterozygous state. They presented with global developmental delay, moderate or severe cognitive impairment, progressive spasticity, ataxia, and seizures. In addition, cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy.

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature; to: PMID:39753114 reported nine different individuals from eight unrelated families with a selenopathy with early-onset neurodegeneration. Thy were all identified with six different biallelic variants in EEFSEC gene, of which seven families had variants in homozygous state, while one family had variants in compound heterozygous state. They presented with global developmental delay, moderate or severe cognitive impairment, progressive spasticity, ataxia, and seizures. In addition, cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy. Ataxia was reported in four unrelated cases, cerebellar hypoplasia in one and cerebellar atrophy in four cases from three families.

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v7.14 EEFSEC Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: EEFSEC.
Ataxia and cerebellar anomalies - narrow panel v7.14 EEFSEC Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39753114 paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Ataxia and cerebellar anomalies - narrow panel v7.14 EEFSEC Achchuthan Shanmugasundram Publications for gene: EEFSEC were set to 39753114
Ataxia and cerebellar anomalies - narrow panel v7.13 EEFSEC Achchuthan Shanmugasundram Phenotypes for gene: EEFSEC were changed from neuroseselopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; hereditary cerebellar ataxia, MONDO:0100310
Ataxia and cerebellar anomalies - narrow panel v7.12 EEFSEC Achchuthan Shanmugasundram edited their review of gene: EEFSEC: Changed phenotypes to: neurodevelopmental disorder, MONDO:0700092, hereditary cerebellar ataxia, MONDO:0100310
Early onset or syndromic epilepsy v7.27 EEFSEC Achchuthan Shanmugasundram Classified gene: EEFSEC as Amber List (moderate evidence)
Early onset or syndromic epilepsy v7.27 EEFSEC Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (six unrelated families) for the promotion of this gene to green rating in the next GMS update.
Early onset or syndromic epilepsy v7.27 EEFSEC Achchuthan Shanmugasundram Gene: eefsec has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v7.26 EEFSEC Achchuthan Shanmugasundram changed review comment from: PMID:39753114 reported nine different individuals from eight unrelated families with a selenopathy with early-onset neurodegeneration. Thy were all identified with six different biallelic variants in EEFSEC gene, of which seven families had variants in homozygous state, while one family had variants in compound heterozygous state. They presented with global developmental delay, moderate or severe cognitive impairment, progressive spasticity, ataxia, and seizures. In addition, cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy.

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature; to: PMID:39753114 reported nine different individuals from eight unrelated families with a selenopathy with early-onset neurodegeneration. Thy were all identified with six different biallelic variants in EEFSEC gene, of which seven families had variants in homozygous state, while one family had variants in compound heterozygous state. They presented with global developmental delay, moderate or severe cognitive impairment, progressive spasticity, ataxia, and seizures. In addition, cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy. Seizures were reported in seven patients from six families.

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Early onset or syndromic epilepsy v7.26 EEFSEC Achchuthan Shanmugasundram Phenotypes for gene: EEFSEC were changed from neuroseselopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; epilepsy, MONDO:0005027
Early onset or syndromic epilepsy v7.25 EEFSEC Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: EEFSEC.
Early onset or syndromic epilepsy v7.25 EEFSEC Achchuthan Shanmugasundram changed review comment from: PMID:39753114 reported nine different individuals from eight unrelated families with a selenopathy with early-onset neurodegeneration. Thy were all identified with six different biallelic variants in EEFSEC gene, of which seven families had variants in homozygous state, while one family had variants in compound heterozygous state. They presented with global developmental delay, moderate or severe cognitive impairment, progressive spasticity, ataxia, and seizures. In addition, cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy.

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature; to: PMID:39753114 reported nine different individuals from eight unrelated families with a selenopathy with early-onset neurodegeneration. Thy were all identified with six different biallelic variants in EEFSEC gene, of which seven families had variants in homozygous state, while one family had variants in compound heterozygous state. They presented with global developmental delay, moderate or severe cognitive impairment, progressive spasticity, ataxia, and seizures. In addition, cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy.

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Early onset or syndromic epilepsy v7.25 EEFSEC Achchuthan Shanmugasundram edited their review of gene: EEFSEC: Changed phenotypes to: neurodevelopmental disorder, MONDO:0700092, epilepsy, MONDO:0005027
Early onset or syndromic epilepsy v7.25 EEFSEC Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39753114 paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Early onset or syndromic epilepsy v7.25 EEFSEC Achchuthan Shanmugasundram Publications for gene: EEFSEC were set to 39753114
Intellectual disability v8.57 EEFSEC Achchuthan Shanmugasundram Classified gene: EEFSEC as Amber List (moderate evidence)
Intellectual disability v8.57 EEFSEC Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (eight unrelated families) for the promotion of this gene to green rating in the next GMS update.
Intellectual disability v8.57 EEFSEC Achchuthan Shanmugasundram Gene: eefsec has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.56 EEFSEC Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: EEFSEC.
Intellectual disability v8.56 EEFSEC Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39753114 paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.56 EEFSEC Achchuthan Shanmugasundram Publications for gene: EEFSEC were set to 39753114
Intellectual disability v8.55 EEFSEC Achchuthan Shanmugasundram Phenotypes for gene: EEFSEC were changed from neuroseselopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v8.54 EEFSEC Achchuthan Shanmugasundram edited their review of gene: EEFSEC: Changed phenotypes to: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071
Ataxia and cerebellar anomalies - narrow panel v7.12 EEFSEC Achchuthan Shanmugasundram gene: EEFSEC was added
gene: EEFSEC was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: EEFSEC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EEFSEC were set to 39753114
Phenotypes for gene: EEFSEC were set to neuroseselopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: EEFSEC was set to GREEN
Added comment: PMID:39753114 reported nine different individuals from eight unrelated families with a selenopathy with early-onset neurodegeneration. Thy were all identified with six different biallelic variants in EEFSEC gene, of which seven families had variants in homozygous state, while one family had variants in compound heterozygous state. They presented with global developmental delay, moderate or severe cognitive impairment, progressive spasticity, ataxia, and seizures. In addition, cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy.

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Early onset or syndromic epilepsy v7.24 EEFSEC Achchuthan Shanmugasundram gene: EEFSEC was added
gene: EEFSEC was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: EEFSEC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EEFSEC were set to 39753114
Phenotypes for gene: EEFSEC were set to neuroseselopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: EEFSEC was set to GREEN
Added comment: PMID:39753114 reported nine different individuals from eight unrelated families with a selenopathy with early-onset neurodegeneration. Thy were all identified with six different biallelic variants in EEFSEC gene, of which seven families had variants in homozygous state, while one family had variants in compound heterozygous state. They presented with global developmental delay, moderate or severe cognitive impairment, progressive spasticity, ataxia, and seizures. In addition, cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy.

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v8.54 EEFSEC Achchuthan Shanmugasundram gene: EEFSEC was added
gene: EEFSEC was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: EEFSEC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EEFSEC were set to 39753114
Phenotypes for gene: EEFSEC were set to neuroseselopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: EEFSEC was set to GREEN
Added comment: PMID:39753114 reported nine different individuals from eight unrelated families with a selenopathy with early-onset neurodegeneration. Thy were all identified with six different biallelic variants in EEFSEC gene, of which seven families had variants in homozygous state, while one family had variants in compound heterozygous state. They presented with global developmental delay, moderate or severe cognitive impairment, progressive spasticity, ataxia, and seizures. In addition, cerebral MRI primarily demonstrated a cerebellar pathology, including hypoplasia and progressive atrophy.

This gene has not yet been associated with any relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Severe microcephaly v7.10 WDR47 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39609633 paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Severe microcephaly v7.10 WDR47 Achchuthan Shanmugasundram Publications for gene: WDR47 were set to 39609633
Severe microcephaly v7.9 WDR47 Achchuthan Shanmugasundram Classified gene: WDR47 as Amber List (moderate evidence)
Severe microcephaly v7.9 WDR47 Achchuthan Shanmugasundram Gene: wdr47 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v7.8 WDR47 Achchuthan Shanmugasundram Phenotypes for gene: WDR47 were changed from neuronevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; microcephaly, MONDO:0001149
Severe microcephaly v7.7 WDR47 Achchuthan Shanmugasundram edited their review of gene: WDR47: Changed phenotypes to: neurodevelopmental disorder, MONDO:0700092, microcephaly, MONDO:0001149
Severe microcephaly v7.7 WDR47 Achchuthan Shanmugasundram changed review comment from: PMID:39609633 reported seven patients from five unrelated families with either homozygous or compound heterozygous variants in WDR47 gene. They all presented with a complex neurodevelopmental syndrome comprising corpus callosum dysgenesis, microcephaly, intellectual disability and epilepsy. Profound intellectual disability was present in four of five reported families.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature; to: PMID:39609633 reported seven patients from five unrelated families with either homozygous or compound heterozygous variants in WDR47 gene. They all presented with a complex neurodevelopmental syndrome comprising corpus callosum dysgenesis, microcephaly, intellectual disability and epilepsy. Microcephaly was found in all cases, but it was only severe (beyond 3 SD) in two unrelated cases. Hence, this gene can only be rated amber with current evidence on this panel.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Severe microcephaly v7.7 WDR47 Achchuthan Shanmugasundram edited their review of gene: WDR47: Changed rating: AMBER; Changed phenotypes to: neuronevelopmental disorder, MONDO:0700092, microcephaly, MONDO:0001149
Early onset or syndromic epilepsy v7.23 WDR47 Achchuthan Shanmugasundram Classified gene: WDR47 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v7.23 WDR47 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (five unrelated families) for the promotion of this gene to green rating on the next GMS update.
Early onset or syndromic epilepsy v7.23 WDR47 Achchuthan Shanmugasundram Gene: wdr47 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v7.22 WDR47 Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: WDR47.
Early onset or syndromic epilepsy v7.22 WDR47 Achchuthan Shanmugasundram changed review comment from: PMID:39609633 reported seven patients from five unrelated families with either homozygous or compound heterozygous variants in WDR47 gene. They all presented with a complex neurodevelopmental syndrome comprising corpus callosum dysgenesis, microcephaly, intellectual disability and epilepsy. Profound intellectual disability was present in four of five reported families.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature; to: PMID:39609633 reported seven patients from five unrelated families with either homozygous or compound heterozygous variants in WDR47 gene. They all presented with a complex neurodevelopmental syndrome comprising corpus callosum dysgenesis, microcephaly, intellectual disability and epilepsy. Seizures were present in all five reported families.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Early onset or syndromic epilepsy v7.22 WDR47 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39609633 paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Early onset or syndromic epilepsy v7.22 WDR47 Achchuthan Shanmugasundram Publications for gene: WDR47 were set to 39609633
Early onset or syndromic epilepsy v7.21 WDR47 Achchuthan Shanmugasundram Phenotypes for gene: WDR47 were changed from neuronevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; epilepsy, MONDO:0005027
Early onset or syndromic epilepsy v7.20 WDR47 Achchuthan Shanmugasundram edited their review of gene: WDR47: Changed phenotypes to: neurodevelopmental disorder, MONDO:0700092, epilepsy, MONDO:0005027
Intellectual disability v8.53 WDR47 Achchuthan Shanmugasundram Phenotypes for gene: WDR47 were changed from neuronevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v8.52 WDR47 Achchuthan Shanmugasundram edited their review of gene: WDR47: Changed phenotypes to: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071
Intellectual disability v8.52 WDR47 Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v8.52 WDR47 Achchuthan Shanmugasundram Classified gene: WDR47 as Amber List (moderate evidence)
Intellectual disability v8.52 WDR47 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (four unrelated families) for the promotion of this gene to green rating on the next GMS update.
Intellectual disability v8.52 WDR47 Achchuthan Shanmugasundram Gene: wdr47 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.51 WDR47 Achchuthan Shanmugasundram Classified gene: WDR47 as Amber List (moderate evidence)
Intellectual disability v8.51 WDR47 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (four unrelated families) for the promotion of this gene to green rating on the next GMS update.
Intellectual disability v8.51 WDR47 Achchuthan Shanmugasundram Gene: wdr47 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.50 WDR47 Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: WDR47.
Intellectual disability v8.50 WDR47 Achchuthan Shanmugasundram Added comment: Comment on publications: PMID:39609633 paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Intellectual disability v8.50 WDR47 Achchuthan Shanmugasundram Publications for gene: WDR47 were set to 39609633
Severe microcephaly v7.7 WDR47 Achchuthan Shanmugasundram gene: WDR47 was added
gene: WDR47 was added to Severe microcephaly. Sources: Literature
Mode of inheritance for gene: WDR47 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR47 were set to 39609633
Phenotypes for gene: WDR47 were set to neuronevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: WDR47 was set to GREEN
Added comment: PMID:39609633 reported seven patients from five unrelated families with either homozygous or compound heterozygous variants in WDR47 gene. They all presented with a complex neurodevelopmental syndrome comprising corpus callosum dysgenesis, microcephaly, intellectual disability and epilepsy. Profound intellectual disability was present in four of five reported families.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Early onset or syndromic epilepsy v7.20 WDR47 Achchuthan Shanmugasundram gene: WDR47 was added
gene: WDR47 was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: WDR47 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR47 were set to 39609633
Phenotypes for gene: WDR47 were set to neuronevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: WDR47 was set to GREEN
Added comment: PMID:39609633 reported seven patients from five unrelated families with either homozygous or compound heterozygous variants in WDR47 gene. They all presented with a complex neurodevelopmental syndrome comprising corpus callosum dysgenesis, microcephaly, intellectual disability and epilepsy. Profound intellectual disability was present in four of five reported families.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Intellectual disability v8.49 WDR47 Achchuthan Shanmugasundram gene: WDR47 was added
gene: WDR47 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: WDR47 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR47 were set to 39609633
Phenotypes for gene: WDR47 were set to neuronevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Review for gene: WDR47 was set to GREEN
Added comment: PMID:39609633 reported seven patients from five unrelated families with either homozygous or compound heterozygous variants in WDR47 gene. They all presented with a complex neurodevelopmental syndrome comprising corpus callosum dysgenesis, microcephaly, intellectual disability and epilepsy. Profound intellectual disability was present in four of five reported families.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Inherited ovarian cancer (without breast cancer) v4.3 LLGL2 Riyaad Aungraheeta gene: LLGL2 was added
gene: LLGL2 was added to Inherited ovarian cancer (without breast cancer). Sources: Literature
Mode of inheritance for gene: LLGL2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: LLGL2 were set to 39794353
Phenotypes for gene: LLGL2 were set to High-grade serous ovarian carcinoma
Penetrance for gene: LLGL2 were set to unknown
Review for gene: LLGL2 was set to AMBER
Added comment: Sources: Literature
Skeletal dysplasia v7.16 SIK3 Ronnie Wright gene: SIK3 was added
gene: SIK3 was added to Skeletal dysplasia. Sources: NHS GMS
Mode of inheritance for gene: SIK3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SIK3 were set to 30232230; 22318228
Penetrance for gene: SIK3 were set to Complete
Review for gene: SIK3 was set to AMBER
gene: SIK3 was marked as current diagnostic
Added comment: Literature:
PMID:30232230 - 2 sibs affected with metaphyseal dysplasia, alongside other phenotypes (developmental delay with brain MRI abnormalities, a severe unclassified immunodeficiency) homozygous for NM_001366686.3(SIK3):c.559C>T p.(Arg187Cys), referred to as R129C in the publication - shown to affect kinase activity

Clinical/diagnostic testing:
Homozygous duplication (Exon 2-4 - no RNA but predicted out of frame insertion) in GMS clinical testing (off panel/untiered) in patient with with spondylometaphyseal skeletal dysplasia alongside global developmental delay, focal seizures, tetralogy of fallot (CVA-120418-1)

A possible 3rd family would provide support for green rating (details unknown- ?prenatally detected skeletal anomalies, see SIK3 review in fetal anomalies gene panel (https://panelapp.genomicsengland.co.uk/panels/478/gene/SIK3/)

Animal Model:
Association with skeletal dysplasia supported by mouse model evidence PMID:22318228
Sources: NHS GMS
Ataxia and cerebellar anomalies - narrow panel v7.11 MFSD8 Eleanor Williams Tag Q1_25_ NHS_review was removed from gene: MFSD8.
Hereditary ataxia with onset in adulthood v7.8 MFSD8 Eleanor Williams Tag Q1_25_ NHS_review was removed from gene: MFSD8.
Skeletal dysplasia v7.16 BTRC Eleanor Williams Tag cnv tag was added to gene: BTRC.
Tag microduplication tag was added to gene: BTRC.
Limb disorders v6.8 BTRC Eleanor Williams Publications for gene: BTRC were set to 12913067; 29263051; 28777841; 28422522; 27600068; 23596994; 16691619
Limb disorders v6.7 BTRC Eleanor Williams Phenotypes for gene: BTRC were changed from Split-hand split-foot malformation 3 to Split-hand/foot malformation 3, gene duplication syndrome, OMIM:246560; split hand-foot malformation 3, MONDO:0009525
Limb disorders v6.6 BTRC Eleanor Williams edited their review of gene: BTRC: Added comment: PMID: 35908152 - Qui et al 2022 - using trio clinical exome sequencing, a 120 kb microduplication containing only BTRC were identified in a Chinese family affected with SHFM3. The duplication co-segregated with SHFM phenotypes in the family. Transcription levels of BTRC mRNA in lymphocytes of the proband was significantly higher than in the healthy control.

PMID: 36928426 Cova et al 2023 - show that the Lbx1/Fgf8 locus consists of two separate, but interacting, regulatory domains. By re-engineering a human SHFM3-associated duplication in mice they observed ectopic interactions between the Fgf8 apical ectodermal ridge (AER) enhancers and two other genes in the locus, Lbx1 and Btrc. The same ectopic interactions were present in fibroblasts from a SHFM3 affected individual with duplication. In mice with the duplication a limb malformation was not observed. They also report a case of SHFM3 malformation associated with an inversion encompassing the DPDC, POLL and FBXW4 genes which when re-engineered in mice results in increased expression of genes, Lbx1 and Btrc, in an Fgf8-like pattern in the apical ectodermal ridge. Mice with the inversion were observed to have a digit phenotype.

In conclusion, point mutations in BTRC in association with SHFM3 have not been reported. It appears that changed expression of gene BTRC is related to the phenotype, but that expression levels can be impacted by both duplication of the region itself and inversion of other nearby regions, likely by disruption of regulatory domains.; Changed publications to: 35908152, 36928426
Skeletal dysplasia v7.16 BTRC Eleanor Williams Classified gene: BTRC as Amber List (moderate evidence)
Skeletal dysplasia v7.16 BTRC Eleanor Williams Added comment: Comment on list classification: Rating this gene as amber as there is some evidence that duplications encompassing this gene as well as nearby re-arrangements which may impact the expression of this gene, are linked to Split-hand/foot malformation 3.
Skeletal dysplasia v7.16 BTRC Eleanor Williams Gene: btrc has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v7.15 BTRC Eleanor Williams gene: BTRC was added
gene: BTRC was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: BTRC was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: BTRC were set to 19584065; 18067070; 12913067; 16681918; 27600068; 30622331; 35908152; 36928426; 18392654
Phenotypes for gene: BTRC were set to Split-hand/foot malformation 3, gene duplication syndrome, OMIM:246560; split hand-foot malformation 3, MONDO:0009525
Mode of pathogenicity for gene: BTRC was set to Other
Review for gene: BTRC was set to AMBER
Added comment: In OMIM Split-hand/foot malformation 3, gene duplication syndrome (OMIM:246560) is linked to a duplication at 10q24q25 inherited in an autosomal dominant manner and is characterized by the absence of central digits. Gene2Phenotype and ClinGen do not list this gene associated with any phenotype.

Multiple publications have reported patients with SHFM3 and rearrangements covering a 500 kb region encompassing five genes of the locus (LBX1, BTRC, POLL, DPCD, and a partial portion of FBXW4) but excluding the neighbouring FGF8 e.g. PMID: 12913067 (2003), PMID: 16681918 (2006). Subsequent reports have reported various re-arrangements involving different sets of genes in the region. Examples are:

PMID: 27600068 Li et al 2015 - mapped the breakpoints of cases with duplications in the 10q24 region with and without a SHFM3 phenotype and concluded that the critical region responsible for the SHFM phenotypes is most likely located at exon 1 of BTRC gene, which is duplicated in all cases with SHFM phenotypes.

PMID: 30622331 Holder-Espinasse et al 2019 - used array CGH or qPCR to analyse 32 new index cases of 10q24 duplication (22 SHFM including 3 with preaxial polydactyly, 7 monodactylies and 3 patients presenting overlapping phenotypes). 17 cases were familial and 15 occurred de novo. Studies in 4 families showed that the duplication segregated with the phenotype. All cases tested by array-CGH had duplication of at least BTRC and POLL genes. Seven cases had duplication of LBX1 gene as well and 12 patients had duplications comprising the FBXW4 gene (although partially for cases 24 and 27).

PMID: 35908152 - Qui et al 2022 - using trio clinical exome sequencing, a 120 kb microduplication containing only BTRC were identified in a Chinese family affected with SHFM3. The duplication co-segregated with SHFM phenotypes in the family. Transcription levels of BTRC mRNA in lymphocytes of the proband was significantly higher than in the healthy control.

PMID: 36928426 Cova et al 2023 - show that the Lbx1/Fgf8 locus consists of two separate, but interacting, regulatory domains. By re-engineering a human SHFM3-associated duplication in mice they observed ectopic interactions between the Fgf8 apical ectodermal ridge (AER) enhancers and two other genes in the locus, Lbx1 and Btrc. The same ectopic interactions were present in fibroblasts from a SHFM3 affected individual with duplication. In mice with the duplication a limb malformation was not observed. They also report a case of SHFM3 malformation associated with an inversion encompassing the DPDC, POLL and FBXW4 genes which when re-engineered in mice results in increased expression of genes, Lbx1 and Btrc, in an Fgf8-like pattern in the apical ectodermal ridge. Mice with the inversion were observed to have a digit phenotype.

In conclusion, point mutations in BTRC in association with SHFM3 have not been reported. It appears that changed expression of gene BTRC is related to the phenotype, but that expression levels can be impacted by both duplication of the region itself and inversion of other nearby regions, likely by disruption of regulatory domains.
Sources: Literature
Skeletal dysplasia v7.14 FBXW4 Eleanor Williams Phenotypes for gene: FBXW4 were changed from Split-hand/foot malformation 3 syndrome, OMIM:246560; split hand-foot malformation 3, MONDO:0009525 to Split-hand/foot malformation 3, gene duplication syndrome, OMIM:246560; split hand-foot malformation 3, MONDO:0009525
Limb disorders v6.6 FBXW4 Eleanor Williams Phenotypes for gene: FBXW4 were changed from Split-hand/foot malformation 3 syndrome, OMIM:246560; split hand-foot malformation 3, MONDO:0009525 to Split-hand/foot malformation 3, gene duplication syndrome, OMIM:246560; split hand-foot malformation 3, MONDO:0009525
Limb disorders v6.5 FBXW4 Eleanor Williams Publications for gene: FBXW4 were set to 19584065; 18067070
Skeletal dysplasia v7.13 FBXW4 Eleanor Williams Publications for gene: FBXW4 were set to 19584065; 18067070
Limb disorders v6.4 FBXW4 Eleanor Williams Entity copied from Skeletal dysplasia v7.12
Limb disorders v6.4 FBXW4 Eleanor Williams gene: FBXW4 was added
gene: FBXW4 was added to Limb disorders. Sources: Expert list,Emory Genetics Laboratory,Expert Review Amber,Illumina TruGenome Clinical Sequencing Services,UKGTN
Mode of inheritance for gene: FBXW4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FBXW4 were set to 19584065; 18067070
Phenotypes for gene: FBXW4 were set to Split-hand/foot malformation 3 syndrome, OMIM:246560; split hand-foot malformation 3, MONDO:0009525
Penetrance for gene: FBXW4 were set to Complete
Skeletal dysplasia v7.12 FBXW4 Eleanor Williams Source was removed from FBXW4.
Skeletal dysplasia v7.11 FBXW4 Eleanor Williams Tag currently-ngs-unreportable was removed from gene: FBXW4.
Skeletal dysplasia v7.11 FBXW4 Eleanor Williams Classified gene: FBXW4 as Amber List (moderate evidence)
Skeletal dysplasia v7.11 FBXW4 Eleanor Williams Added comment: Comment on list classification: Promoting to amber. There is some evidence from both patient cases and mouse models that disruptions within this gene can result in a split-hand/foot malformation phenotype. However, it is not clear exactly which disruptions are causative since duplications frequently span more than this gene.
Skeletal dysplasia v7.11 FBXW4 Eleanor Williams Gene: fbxw4 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v7.10 FBXW4 Eleanor Williams Phenotypes for gene: FBXW4 were changed from Split-hand/foot malformation 3 syndrome 246560 to Split-hand/foot malformation 3 syndrome, OMIM:246560; split hand-foot malformation 3, MONDO:0009525
Skeletal dysplasia v7.9 FBXW4 Eleanor Williams Mode of inheritance for gene: FBXW4 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Skeletal dysplasia v7.8 FBXW4 Eleanor Williams changed review comment from: In OMIM Split-hand/foot malformation 3, gene duplication syndrome (OMIM:246560) is linked to a duplication at 10q24q25 inherited in an autosomal dominant manner and is characterized by the absence of central digits.

Multiple publications have reported patients with SHFM3 and rearrangements covering a 500 kb region encompassing five genes of the locus (LBX1, BTRC, POLL, DPCD, and a partial portion of FBXW4) but excluding the neighbouring FGF8 e.g. PMID: 12913067 (2003), PMID: 16681918 (2006). Subsequent reports have reported various re-arrangements involving different sets of genes in the region. Examples are:

PMID: 27600068 Li et al 2015 - mapped the breakpoints of cases with duplications in the 10q24 region with and without a SHFM3 phenotype and concluded that the critical region responsible for the SHFM phenotypes is most likely located at exon 1 of BTRC gene, which is duplicated in all cases with SHFM phenotypes.

PMID: 30622331 Holder-Espinasse et al 2019 - used array CGH or qPCR to analyse 32 new index cases of 10q24 duplication (22 SHFM including 3 with preaxial polydactyly, 7 monodactylies and 3 patients presenting overlapping phenotypes). 17 cases were familial and 15 occurred de novo. Studies in 4 families showed that the duplication segregated with the phenotype. All cases tested by array-CGH had duplication of at least BTRC and POLL genes. Seven cases had duplication of LBX1 gene as well and 12 patients had duplications comprising the FBXW4 gene (although partially for cases 24 and 27).

PMID: 35908152 - Qui et al 2022 - using trio clinical exome sequencing, a 120 kb microduplication containing only BTRC were identified in a Chinese family affected with SHFM3. The duplication co-segregated with SHFM phenotypes in the family. Transcription levels of BTRC mRNA in lymphocytes of the proband was significantly higher than in the healthy control.

PMID: 36928426 Cova et al 2023 - show that the Lbx1/Fgf8 locus consists of two separate, but interacting, regulatory domains. By re-engineering a human SHFM3-associated duplication in mice they observed ectopic interactions between the Fgf8 apical ectodermal ridge (AER) enhancers and two other genes in the locus, Lbx1 and Btrc. The same ectopic interactions were present in fibroblasts from a SHFM3 affected individual with duplication. In mice with the duplication a limb malformation was not observed. They also report a case of SHFM3 malformation associated with an inversion encompassing the DPDC, POLL and FBXW4 genes which when re-engineered in mice results in increased expression of genes, Lbx1 and Btrc, in an Fgf8-like pattern in the apical ectodermal ridge. Mice with the inversion were observed to have a digit phenotype.

Mouse model:
PMID: 18392654 - Friedli et al 2008 - show that in Dactylaplasia mice which show a digital phenotype both Dac1j and Dac2j alleles are caused by insertions of MusD retroelements either within or close to the gene Fbxw4. They propose that both mutations result in complex alterations of gene regulation.

In conclusion, point mutations in FBXW4 in association with SHFM3 have not been reported. It appears that changed expression of gene BTRC is related to the phenotype, but that expression levels can be impacted by both duplication of the region itself and inversion of other nearby regions, by disruption of regulatory domains.; to: In OMIM Split-hand/foot malformation 3, gene duplication syndrome (OMIM:246560) is linked to a duplication at 10q24q25 inherited in an autosomal dominant manner and is characterized by the absence of central digits. In Gene2Phenotype the association of FBXW4 with SHFM3 has been rated limited. ClinGen report no evidence for haplo or triplosensitivity in relation to SHFM3 but this has not been re-assessed since 2014.

Multiple publications have reported patients with SHFM3 and rearrangements covering a 500 kb region encompassing five genes of the locus (LBX1, BTRC, POLL, DPCD, and a partial portion of FBXW4) but excluding the neighbouring FGF8 e.g. PMID: 12913067 (2003), PMID: 16681918 (2006). Subsequent reports have reported various re-arrangements involving different sets of genes in the region. Examples are:

PMID: 27600068 Li et al 2015 - mapped the breakpoints of cases with duplications in the 10q24 region with and without a SHFM3 phenotype and concluded that the critical region responsible for the SHFM phenotypes is most likely located at exon 1 of BTRC gene, which is duplicated in all cases with SHFM phenotypes.

PMID: 30622331 Holder-Espinasse et al 2019 - used array CGH or qPCR to analyse 32 new index cases of 10q24 duplication (22 SHFM including 3 with preaxial polydactyly, 7 monodactylies and 3 patients presenting overlapping phenotypes). 17 cases were familial and 15 occurred de novo. Studies in 4 families showed that the duplication segregated with the phenotype. All cases tested by array-CGH had duplication of at least BTRC and POLL genes. Seven cases had duplication of LBX1 gene as well and 12 patients had duplications comprising the FBXW4 gene (although partially for cases 24 and 27).

PMID: 35908152 - Qui et al 2022 - using trio clinical exome sequencing, a 120 kb microduplication containing only BTRC were identified in a Chinese family affected with SHFM3. The duplication co-segregated with SHFM phenotypes in the family. Transcription levels of BTRC mRNA in lymphocytes of the proband was significantly higher than in the healthy control.

PMID: 36928426 Cova et al 2023 - show that the Lbx1/Fgf8 locus consists of two separate, but interacting, regulatory domains. By re-engineering a human SHFM3-associated duplication in mice they observed ectopic interactions between the Fgf8 apical ectodermal ridge (AER) enhancers and two other genes in the locus, Lbx1 and Btrc. The same ectopic interactions were present in fibroblasts from a SHFM3 affected individual with duplication. In mice with the duplication a limb malformation was not observed. They also report a case of SHFM3 malformation associated with an inversion encompassing the DPDC, POLL and FBXW4 genes which when re-engineered in mice results in increased expression of genes, Lbx1 and Btrc, in an Fgf8-like pattern in the apical ectodermal ridge. Mice with the inversion were observed to have a digit phenotype.

Mouse model:
PMID: 18392654 - Friedli et al 2008 - show that in Dactylaplasia mice which show a digital phenotype both Dac1j and Dac2j alleles are caused by insertions of MusD retroelements either within or close to the gene Fbxw4. They propose that both mutations result in complex alterations of gene regulation.

In conclusion, point mutations in FBXW4 in association with SHFM3 have not been reported. It appears that changed expression of gene BTRC is related to the phenotype, but that expression levels can be impacted by both duplication of the region itself and inversion of other nearby regions which include FBXW4, likely by disruption of regulatory domains.
Skeletal dysplasia v7.8 FBXW4 Eleanor Williams changed review comment from: In OMIM Split-hand/foot malformation 3, gene duplication syndrome (OMIM:246560) is linked to a duplication at 10q24q25 inherited in an autosomal dominant manner and is characterized by the absence of central digits.

Multiple publications have reported patients with SHFM3 and rearrangements covering a 500 kb region encompassing five genes of the locus (LBX1, BTRC, POLL, DPCD, and a partial portion of FBXW4) but excluding the neighbouring FGF8 e.g. PMID: 12913067 (2003), PMID: 16681918 (2006). Subsequent reports have reported various duplications involving different sets of genes:

PMID: 27600068 Li et al 2015 - mapped the breakpoints of cases with duplications in the 10q24 region with and without a SHFM3 phenotype and concluded that the critical region responsible for the SHFM phenotypes is most likely located at exon 1 of BTRC gene, which is duplicated in all cases with SHFM phenotypes.


PMID: 30622331 Holder-Espinasse et al 2019 - used array CGH or qPCR to analyse 32 new index cases of 10q24 duplication (22 SHFM including 3 with preaxial polydactyly, 7 monodactylies and 3 patients presenting overlapping phenotypes). 17 cases were familial and 15 occurred de novo. Studies in 4 families showed that the duplication segregated with the phenotype. All cases tested by array-CGH had duplication of at least BTRC and POLL genes. Seven cases had duplication of LBX1 gene as well and 12 patients had duplications comprising the FBXW4 gene (although partially for cases 24 and 27).

PMID: 35908152 - Qui et al 2022 - using trio clinical exome sequencing, a 120 kb microduplication containing only BTRC were identified in a Chinese family affected with SHFM3. The duplication co-segregated with SHFM phenotypes in the family. Transcription levels of BTRC mRNA in lymphocytes of the proband was significantly higher than that in the healthy control.

PMID: 36928426 Cova et al 2023 - show that the Lbx1/Fgf8 locus consists of two separate, but interacting, regulatory domains. By re-engineering a human SHFM3-associated duplication in mice they observed ectopic interactions between the Fgf8 apical ectodermal ridge (AER) enhancers and two other genes in the locus, Lbx1 and Btrc. The same ectopic interactions were present in fibroblasts from a SHFM3 affected individual with duplication. In mice with the duplication a limb malformation was not observed. They also report a case of SHFM3 malformation associated with an inversion encompassing the DPDC, POLL and FBXW4 genes which when re-engineered in mice results in increased expression of genes, Lbx1 and Btrc, in an Fgf8-like pattern in the apical ectodermal ridge. Mice with the inversion were observed to have a digit phenotype.

Mouse model:
PMID: 18392654 - Friedli et al 2008 - show that in Dactylaplasia mice which show a digital phenotype both Dac1j and Dac2j alleles are caused by insertions of MusD retroelements either within or close to the gene Fbxw4. They propose that both mutations result in complex alterations of gene regulation.

In conclusion, point mutations in FBXW4 in association with SHFM3 have not been reported. It appears that expression of gene BTRC is related to the phenotype, but that expression levels can be impacted by both duplication of the region itself and inversion of other nearby regions, by disruption of regulatory domains.; to: In OMIM Split-hand/foot malformation 3, gene duplication syndrome (OMIM:246560) is linked to a duplication at 10q24q25 inherited in an autosomal dominant manner and is characterized by the absence of central digits.

Multiple publications have reported patients with SHFM3 and rearrangements covering a 500 kb region encompassing five genes of the locus (LBX1, BTRC, POLL, DPCD, and a partial portion of FBXW4) but excluding the neighbouring FGF8 e.g. PMID: 12913067 (2003), PMID: 16681918 (2006). Subsequent reports have reported various re-arrangements involving different sets of genes in the region. Examples are:

PMID: 27600068 Li et al 2015 - mapped the breakpoints of cases with duplications in the 10q24 region with and without a SHFM3 phenotype and concluded that the critical region responsible for the SHFM phenotypes is most likely located at exon 1 of BTRC gene, which is duplicated in all cases with SHFM phenotypes.

PMID: 30622331 Holder-Espinasse et al 2019 - used array CGH or qPCR to analyse 32 new index cases of 10q24 duplication (22 SHFM including 3 with preaxial polydactyly, 7 monodactylies and 3 patients presenting overlapping phenotypes). 17 cases were familial and 15 occurred de novo. Studies in 4 families showed that the duplication segregated with the phenotype. All cases tested by array-CGH had duplication of at least BTRC and POLL genes. Seven cases had duplication of LBX1 gene as well and 12 patients had duplications comprising the FBXW4 gene (although partially for cases 24 and 27).

PMID: 35908152 - Qui et al 2022 - using trio clinical exome sequencing, a 120 kb microduplication containing only BTRC were identified in a Chinese family affected with SHFM3. The duplication co-segregated with SHFM phenotypes in the family. Transcription levels of BTRC mRNA in lymphocytes of the proband was significantly higher than in the healthy control.

PMID: 36928426 Cova et al 2023 - show that the Lbx1/Fgf8 locus consists of two separate, but interacting, regulatory domains. By re-engineering a human SHFM3-associated duplication in mice they observed ectopic interactions between the Fgf8 apical ectodermal ridge (AER) enhancers and two other genes in the locus, Lbx1 and Btrc. The same ectopic interactions were present in fibroblasts from a SHFM3 affected individual with duplication. In mice with the duplication a limb malformation was not observed. They also report a case of SHFM3 malformation associated with an inversion encompassing the DPDC, POLL and FBXW4 genes which when re-engineered in mice results in increased expression of genes, Lbx1 and Btrc, in an Fgf8-like pattern in the apical ectodermal ridge. Mice with the inversion were observed to have a digit phenotype.

Mouse model:
PMID: 18392654 - Friedli et al 2008 - show that in Dactylaplasia mice which show a digital phenotype both Dac1j and Dac2j alleles are caused by insertions of MusD retroelements either within or close to the gene Fbxw4. They propose that both mutations result in complex alterations of gene regulation.

In conclusion, point mutations in FBXW4 in association with SHFM3 have not been reported. It appears that changed expression of gene BTRC is related to the phenotype, but that expression levels can be impacted by both duplication of the region itself and inversion of other nearby regions, by disruption of regulatory domains.
Skeletal dysplasia v7.8 FBXW4 Eleanor Williams changed review comment from: In OMIM Split-hand/foot malformation 3, gene duplication syndrome (OMIM:246560) is linked to a duplication at 10q24q25 inherited in an autosomal dominant manner and is characterized by the absence of central digits.

Multiple publications have reported patients with SHFM3 and rearrangements covering a 500 kb region encompassing five genes of the locus (LBX1, BTRC, POLL, DPCD, and a partial portion of FBXW4) but excluding the neighbouring FGF8 e.g. PMID: 12913067 (2003), PMID: 16681918 (2006). Subsequent reports have reported various duplications involving different sets of genes:

PMID: 27600068 Li et al 2015 - mapped the breakpoints of cases with duplications in the 10q24 region with and without a SHFM3 phenotype and concluded that the critical region responsible for the SHFM phenotypes is most likely located at exon 1 of BTRC gene, which is duplicated in all cases with SHFM phenotypes.


PMID: 30622331 Holder-Espinasse et al 2019 - used array CGH or qPCR to analyse 32 new index cases of 10q24 duplication (22 SHFM including 3 with preaxial polydactyly, 7 monodactylies and 3 patients presenting overlapping phenotypes). 17 cases were familial and 15 occurred de novo. Studies in 4 families showed that the duplication segregated with the phenotype. All cases tested by array-CGH had duplication of at least BTRC and POLL genes. Seven cases had duplication of LBX1 gene as well and 12 patients had duplications comprising the FBXW4 gene (although partially for cases 24 and 27).

PMID: 35908152 - Qui et al 2022 - using trio clinical exome sequencing, a 120 kb microduplication containing only BTRC were identified in a Chinese family affected with SHFM3. The duplication co-segregated with SHFM phenotypes in the family. Transcription levels of BTRC mRNA in lymphocyte of the proband was significantly higher than that in the healthy control.

PMID: 36928426 Cova et al 2023 - show that the Lbx1/Fgf8 locus consists of two separate, but interacting, regulatory domains. By re-engineering a human SHFM3-associated duplication in mice they observed ectopic interactions between the Fgf8 apical ectodermal ridge (AER) enhancers and two other genes in the locus, Lbx1 and Btrc. The same ectopic interactions were present in fibroblasts from a SHFM3 affected individual with duplication. In mice with the duplication a limb malformation was not observed. They also report a case of SHFM3 malformation associated with an inversion encompassing the DPDC, POLL and FBXW4 genes which when re-engineered in mice results in increased expression of genes, Lbx1 and Btrc, in an Fgf8-like pattern in the apical ectodermal ridge. Mice with the inversion were observed to have a digit phenotype.

Mouse model:
PMID: 18392654 - Friedli et al 2008 - show that in Dactylaplasia mice which show a digital phenotype both Dac1j and Dac2j are caused by insertions of MusD retroelements either within or close to the gene Fbxw4. They propose that both mutations result in complex alterations of gene regulation.

In conclusion, point mutations in FBXW4 in association with SHFM3 have not been reported. It appears that expression of gene BTRC is related to the phenotype, but that expression levels can be impacted by both duplication of the region itself and inversion of other nearby regions, by disruption of regulatory domains.; to: In OMIM Split-hand/foot malformation 3, gene duplication syndrome (OMIM:246560) is linked to a duplication at 10q24q25 inherited in an autosomal dominant manner and is characterized by the absence of central digits.

Multiple publications have reported patients with SHFM3 and rearrangements covering a 500 kb region encompassing five genes of the locus (LBX1, BTRC, POLL, DPCD, and a partial portion of FBXW4) but excluding the neighbouring FGF8 e.g. PMID: 12913067 (2003), PMID: 16681918 (2006). Subsequent reports have reported various duplications involving different sets of genes:

PMID: 27600068 Li et al 2015 - mapped the breakpoints of cases with duplications in the 10q24 region with and without a SHFM3 phenotype and concluded that the critical region responsible for the SHFM phenotypes is most likely located at exon 1 of BTRC gene, which is duplicated in all cases with SHFM phenotypes.


PMID: 30622331 Holder-Espinasse et al 2019 - used array CGH or qPCR to analyse 32 new index cases of 10q24 duplication (22 SHFM including 3 with preaxial polydactyly, 7 monodactylies and 3 patients presenting overlapping phenotypes). 17 cases were familial and 15 occurred de novo. Studies in 4 families showed that the duplication segregated with the phenotype. All cases tested by array-CGH had duplication of at least BTRC and POLL genes. Seven cases had duplication of LBX1 gene as well and 12 patients had duplications comprising the FBXW4 gene (although partially for cases 24 and 27).

PMID: 35908152 - Qui et al 2022 - using trio clinical exome sequencing, a 120 kb microduplication containing only BTRC were identified in a Chinese family affected with SHFM3. The duplication co-segregated with SHFM phenotypes in the family. Transcription levels of BTRC mRNA in lymphocytes of the proband was significantly higher than that in the healthy control.

PMID: 36928426 Cova et al 2023 - show that the Lbx1/Fgf8 locus consists of two separate, but interacting, regulatory domains. By re-engineering a human SHFM3-associated duplication in mice they observed ectopic interactions between the Fgf8 apical ectodermal ridge (AER) enhancers and two other genes in the locus, Lbx1 and Btrc. The same ectopic interactions were present in fibroblasts from a SHFM3 affected individual with duplication. In mice with the duplication a limb malformation was not observed. They also report a case of SHFM3 malformation associated with an inversion encompassing the DPDC, POLL and FBXW4 genes which when re-engineered in mice results in increased expression of genes, Lbx1 and Btrc, in an Fgf8-like pattern in the apical ectodermal ridge. Mice with the inversion were observed to have a digit phenotype.

Mouse model:
PMID: 18392654 - Friedli et al 2008 - show that in Dactylaplasia mice which show a digital phenotype both Dac1j and Dac2j alleles are caused by insertions of MusD retroelements either within or close to the gene Fbxw4. They propose that both mutations result in complex alterations of gene regulation.

In conclusion, point mutations in FBXW4 in association with SHFM3 have not been reported. It appears that expression of gene BTRC is related to the phenotype, but that expression levels can be impacted by both duplication of the region itself and inversion of other nearby regions, by disruption of regulatory domains.
Skeletal dysplasia v7.8 FBXW4 Eleanor Williams commented on gene: FBXW4
Thoracic aortic aneurysm or dissection (GMS) v3.19 SMAD6 Ian Berry reviewed gene: SMAD6: Rating: RED; Mode of pathogenicity: None; Publications: PMID:22275001, 30796334, 28659821, 36414630); Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v7.19 ADPRHL2 Eleanor Williams Publications for gene: ADPRHL2 were set to 30100084; 30401461
Ataxia and cerebellar anomalies - narrow panel v7.11 ADPRHL2 Eleanor Williams Publications for gene: ADPRHL2 were set to 30100084; 30401461
Structural eye disease v4.1 FOXE3 Dorine Bax reviewed gene: FOXE3: Rating: GREEN; Mode of pathogenicity: Other; Publications: PMID: 21150893, 9708017, 34046667; Phenotypes: HP:0007700, HP:0000568, HP:0007707, HP:0000589, HP:0000519; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Current diagnostic: yes
Skeletal dysplasia v7.8 CTGF Achchuthan Shanmugasundram commented on gene: CTGF: The 'new-gene-name' tag was added as the HGNC approved gene name is CCN2.
Skeletal dysplasia v7.8 CTGF Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: CTGF.
Skeletal dysplasia v7.8 CTGF Achchuthan Shanmugasundram Classified gene: CTGF as Amber List (moderate evidence)
Skeletal dysplasia v7.8 CTGF Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (two unrelated cases and animal models) in support of the association of biallelic variants with kyphomelic dysplasia. However, there is only one family reported with monoallelic variants. Hence, the MOI was set to 'BIALLELIC, autosomal or pseudoautosomal'. It can be promoted to green rating in the next GMS update.
Skeletal dysplasia v7.8 CTGF Achchuthan Shanmugasundram Gene: ctgf has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v7.7 CTGF Achchuthan Shanmugasundram Phenotypes for gene: CTGF were changed from to kyphomelic dysplasia, MONDO:0008881; spondyloepimetaphyseal dysplasia, MONDO:0100510
Skeletal dysplasia v7.6 CTGF Achchuthan Shanmugasundram Publications for gene: CTGF were set to 39506047; 12736220
Skeletal dysplasia v7.5 CTGF Achchuthan Shanmugasundram Tag Q1_25_ promote_green tag was added to gene: CTGF.
Skeletal dysplasia v7.5 CTGF Achchuthan Shanmugasundram reviewed gene: CTGF: Rating: GREEN; Mode of pathogenicity: None; Publications: 12736220, 39414788, 39506047; Phenotypes: kyphomelic dysplasia, MONDO:0008881, spondyloepimetaphyseal dysplasia, MONDO:0100510; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Distal myopathies v6.2 CNBP_CCTG Sarah Leigh changed review comment from: As STR: CNBP_CCTG has been reviewed and confirmed by the NHS Genomic Medicine Service, it can be rated as Green on this panel.; to: As STR: CNBP_CCTG has been reviewed and confirmed by the NHS Genomic Medicine Service, it can be rated as Green on this panel after the next available update.
Paediatric disorders - additional genes v6.10 HMGA2 Achchuthan Shanmugasundram Classified gene: HMGA2 as Amber List (moderate evidence)
Paediatric disorders - additional genes v6.10 HMGA2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Tracy Lester, the phenotypes observed are relevant to R27 Paediatric disorders clinical indication. In addition, this gene is currently missing in DDG2P panel and the phenotypes are not relevant to any other components of R27.

There is sufficient evidence available for green rating and hence this gene should be promoted to green in the next GMS review.
Paediatric disorders - additional genes v6.10 HMGA2 Achchuthan Shanmugasundram Gene: hmga2 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v7.10 MFSD8 Sarah Leigh Tag Q1_25_ NHS_review tag was added to gene: MFSD8.
Tag Q1_25_ promote_green tag was added to gene: MFSD8.
Hereditary ataxia with onset in adulthood v7.8 MFSD8 Sarah Leigh Tag Q1_25_ NHS_review tag was added to gene: MFSD8.
Tag Q1_25_ promote_green tag was added to gene: MFSD8.
Hereditary ataxia with onset in adulthood v7.8 MFSD8 Sarah Leigh Classified gene: MFSD8 as Amber List (moderate evidence)
Hereditary ataxia with onset in adulthood v7.8 MFSD8 Sarah Leigh Gene: mfsd8 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v7.10 MFSD8 Sarah Leigh Classified gene: MFSD8 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v7.10 MFSD8 Sarah Leigh Gene: mfsd8 has been classified as Amber List (Moderate Evidence).
Hereditary ataxia with onset in adulthood v7.7 MFSD8 Sarah Leigh Entity copied from Neuronal ceroid lipofuscinosis v2.8
Hereditary ataxia with onset in adulthood v7.7 MFSD8 Sarah Leigh gene: MFSD8 was added
gene: MFSD8 was added to Hereditary ataxia with onset in adulthood. Sources: NHS GMS,London North GLH,Expert Review Green
Mode of inheritance for gene: MFSD8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MFSD8 were set to Ceroid lipofuscinosis, neuronal, 7 OMIM:610951; neuronal ceroid lipofuscinosis 7 MONDO:0012588
Ataxia and cerebellar anomalies - narrow panel v7.9 MFSD8 Sarah Leigh Entity copied from Neuronal ceroid lipofuscinosis v2.8
Ataxia and cerebellar anomalies - narrow panel v7.9 MFSD8 Sarah Leigh gene: MFSD8 was added
gene: MFSD8 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: NHS GMS,London North GLH,Expert Review Green
Mode of inheritance for gene: MFSD8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MFSD8 were set to Ceroid lipofuscinosis, neuronal, 7 OMIM:610951; neuronal ceroid lipofuscinosis 7 MONDO:0012588
Neuronal ceroid lipofuscinosis v2.8 MFSD8 Sarah Leigh reviewed gene: MFSD8: Rating: GREEN; Mode of pathogenicity: None; Publications: 39108195, 30144815, 19201763; Phenotypes: Ceroid lipofuscinosis, neuronal, 7 OMIM:610951, neuronal ceroid lipofuscinosis 7 MONDO:0012588; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric disorders - additional genes v6.9 HMGA2 Achchuthan Shanmugasundram Phenotypes for gene: HMGA2 were changed from to Silver-Russell syndrome 5, OMIM:618908
Paediatric disorders - additional genes v6.8 HMGA2 Achchuthan Shanmugasundram Publications for gene: HMGA2 were set to
Paediatric disorders - additional genes v6.7 HMGA2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: HMGA2.
Tag Q1_25_ promote_green tag was added to gene: HMGA2.
Paediatric disorders - additional genes v6.7 HMGA2 Achchuthan Shanmugasundram reviewed gene: HMGA2: Rating: GREEN; Mode of pathogenicity: None; Publications: 25809938, 28796236, 29453418, 29655892; Phenotypes: Silver-Russell syndrome 5, OMIM:618908; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v7.1 C19orf44 Andrew Webster gene: C19orf44 was added
gene: C19orf44 was added to Retinal disorders. Sources: Research
Mode of inheritance for gene: C19orf44 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: C19orf44 were set to retinal dystrophy; macular dystrophy; cone-rod dystrophy; rod-cone dystrophy
Penetrance for gene: C19orf44 were set to unknown
Mode of pathogenicity for gene: C19orf44 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: C19orf44 was set to GREEN
Added comment: Publication accepted by Genetics In Medicine, involving four LOF alleles in 15 affected individuals from 11 families, with four centres contributing (Israel, Boston, Basel, London (UCL/MEH)).

GENETMED-D-24-00741R2
Biallelic null variants in C19orf44 cause a unique late onset retinal dystrophy
phenotype characterized by patchy perifoveal chorioretinal atrophy
Sources: Research
Paediatric disorders - additional genes v6.7 PLAG1 Achchuthan Shanmugasundram Phenotypes for gene: PLAG1 were changed from short stature to Silver-Russell syndrome 4, OMIM:618907
Severe early-onset obesity v4.12 STX16 Dmitrijs Rots gene: STX16 was added
gene: STX16 was added to Severe early-onset obesity. Sources: Literature
Mode of inheritance for gene: STX16 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: STX16 were set to PMID: 27338644; 28453643
Phenotypes for gene: STX16 were set to Obesity with pseudohypoparathyroidism type 1B
Penetrance for gene: STX16 were set to Incomplete
Review for gene: STX16 was set to GREEN
Added comment: PMID: 27338644 & PMID: 28453643 shows that STX16 deletions, causing GNAS methylation defects, result in obesity. GNAS is already on this panel as green. Enough evidence for the green rating.
Sources: Literature
Severe early-onset obesity v4.12 MRAP2 Dmitrijs Rots reviewed gene: MRAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 31700171; Phenotypes: obesity; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Severe early-onset obesity v4.12 MC3R Dmitrijs Rots gene: MC3R was added
gene: MC3R was added to Severe early-onset obesity. Sources: Literature
Mode of inheritance for gene: MC3R was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MC3R were set to PMID: 31090190
Phenotypes for gene: MC3R were set to obesity
Penetrance for gene: MC3R were set to Incomplete
Review for gene: MC3R was set to GREEN
Added comment: PMID: 31090190 described a meta analysis of ~3k cases (including children) with obesity & ~2.5k controls and found a significant enrichment of LoF MC3R variants in obesity cases (OR = 3.07). Enough evidence for the green rating.
Sources: Literature
Severe early-onset obesity v4.12 GNB1 Dmitrijs Rots gene: GNB1 was added
gene: GNB1 was added to Severe early-onset obesity. Sources: Literature
Mode of inheritance for gene: GNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: GNB1 were set to PMID: 38596856
Review for gene: GNB1 was set to GREEN
Added comment: 75% of cases with truncating variants present with obesity as described in PMID: 38596856
Sources: Literature
Skeletal dysplasia v7.5 CTGF Cassandra Smith gene: CTGF was added
gene: CTGF was added to Skeletal dysplasia. Sources: Literature
Mode of inheritance for gene: CTGF was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTGF were set to 39506047; 12736220
Review for gene: CTGF was set to GREEN
Added comment: New gene name CCN2

39506047: Two consanguineous families with three affected patients with reported kyphomelic dysplasia. Rare missense (Cys148Tyr )and novel frameshift variant (Pro260LeufsTer7). Zebrafish crispants show skeletal changes.

12736220: Knockout mice show a skeletal phenotype
Sources: Literature
Intellectual disability v8.48 TAOK2 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Nour Elkhateeb, PMID:39737487 reported 10 individuals with monoallelic TAOK2 variants and with a neurodevelopmemntal disorder. Four of these patients were reported with global developmental delay and eight were reported with intellectual disability/ learning difficulties. Hence, this gene can be promoted to green rating in the next GMS update.; to: Comment on list classification: As reviewed by Nour Elkhateeb, PMID:39737487 reported 10 individuals with monoallelic TAOK2 variants and with a neurodevelopmental disorder. Four of these patients were reported with global developmental delay and eight were reported with intellectual disability/ learning difficulties. Hence, this gene can be promoted to green rating in the next GMS update.
Intellectual disability v8.48 TAOK2 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: TAOK2.
Tag Q1_25_ promote_green tag was added to gene: TAOK2.
Intellectual disability v8.48 TAOK2 Achchuthan Shanmugasundram Classified gene: TAOK2 as Amber List (moderate evidence)
Intellectual disability v8.48 TAOK2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Nour Elkhateeb, PMID:39737487 reported 10 individuals with monoallelic TAOK2 variants and with a neurodevelopmemntal disorder. Four of these patients were reported with global developmental delay and eight were reported with intellectual disability/ learning difficulties. Hence, this gene can be promoted to green rating in the next GMS update.
Intellectual disability v8.48 TAOK2 Achchuthan Shanmugasundram Gene: taok2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.47 TAOK2 Achchuthan Shanmugasundram Phenotypes for gene: TAOK2 were changed from Developmental delay; Intellectual disability; Speech and language delay; Autism spectrum disorder to neuronevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v8.47 TAOK2 Achchuthan Shanmugasundram Publications for gene: TAOK2 were set to PMID: 39737487; 29467497
Intellectual disability v8.46 TAOK2 Achchuthan Shanmugasundram reviewed gene: TAOK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 39737487; Phenotypes: neuronevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v8.46 TAOK1 Achchuthan Shanmugasundram Phenotypes for gene: TAOK1 were changed from INTELLECTUAL DISABILITY; developmental delay to Developmental delay with or without intellectual impairment or behavioral abnormalities, OMIM:619575
Paediatric disorders - additional genes v6.6 CACHD1 Achchuthan Shanmugasundram Tag dd_review tag was added to gene: CACHD1.
Monogenic hearing loss v4.66 TUBB4B Achchuthan Shanmugasundram Classified gene: TUBB4B as Amber List (moderate evidence)
Monogenic hearing loss v4.66 TUBB4B Achchuthan Shanmugasundram Added comment: Comment on list classification: There are at least six unrelated patients reported with hearing loss and heterozygous TUBB4B variants. Hence, this gene can be promoted top green rating on the next GMS update.
Monogenic hearing loss v4.66 TUBB4B Achchuthan Shanmugasundram Gene: tubb4b has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.65 TUBB4B Achchuthan Shanmugasundram gene: TUBB4B was added
gene: TUBB4B was added to Monogenic hearing loss. Sources: Literature
dd_review, Q1_25_ promote_green tags were added to gene: TUBB4B.
Mode of inheritance for gene: TUBB4B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB4B were set to 29198720; 38662826; 39115449
Phenotypes for gene: TUBB4B were set to Leber congenital amaurosis with early-onset deafness, OMIM:617879; sensorineural hearing loss disorder, MONDO:0020678
Review for gene: TUBB4B was set to GREEN
Added comment: PMID:29198720 reported three patients of a family with early-onset retinal degeneration and hearing loss and they were identified with a heterozygous missense variant in TUBB4B gene (p.Arg391His).

PMID:38662826 reported a cohort of 12 patients with primary ciliary dyskinesia (PCD) and with heterozygous variants in TUBB4B gene. Four different variants were reported in these patients. Common clinical features of airway disease including chronic wet cough (7/12), recurrent infections (11/12), bronchiectasis (8/12) and rhinosinusitis (9/12) were observed across the cohort/ 6/12 patients were reported with hydrocephaly. Four patients with the p.Pro358Ser variant also presented with Leber congenital amaurosis (LCA) associated with sensorineural hearing loss (SNHL). Similar cellular phenotype was also observed in patient-derived respiratory epithelial cells.

PMID:39115449 reported eight patients with PCD, of which one patient was identified with a de novo variant in TUBB4B gene (p.Pro259Leu). This patient presented with airways disease and hearing loss.

This gene has been associated with Leber congenital amaurosis with early-onset deafness phenotype in OMIM (MIM #617879), but not yet in Gene2Phenotype.
Sources: Literature
Breast cancer pertinent cancer susceptibility v2.12 CDH1 Dmitrijs Rots reviewed gene: CDH1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Respiratory ciliopathies including non-CF bronchiectasis v3.25 TUBB4B Achchuthan Shanmugasundram changed review comment from: PMID:38662826 reported a cohort of 12 patients with primary ciliary dyskinesia (PCD) and with heterozygous variants in TUBB4B gene. Four different variants were reported in these patients. Common clinical features of airway disease including chronic wet cough (7/12), recurrent infections (11/12), bronchiectasis (8/12) and rhinosinusitis (9/12) were observed across the cohort/ 6/12 patients were reported with hydrocephaly. Four patients with the p.Pro358Ser variant also presented with Leber congenital amaurosis (LCA) associated with sensorineural hearing loss (SNHL). Similar cellular phenotype was also observed in patient-derived respiratory epithelial cells.

PMID:39115449 reported eight patients with PCD, of which one patient was identified with a de novo variant in TUBB4B gene.

The PCD phenotype has not yet been reported in OMIM, while LCA phenotype is already associated with TUBB4B in OMIM (MIM #617879).
Sources: Literature; to: PMID:38662826 reported a cohort of 12 patients with primary ciliary dyskinesia (PCD) and with heterozygous variants in TUBB4B gene. Four different variants were reported in these patients. Common clinical features of airway disease including chronic wet cough (7/12), recurrent infections (11/12), bronchiectasis (8/12) and rhinosinusitis (9/12) were observed across the cohort/ 6/12 patients were reported with hydrocephaly. Four patients with the p.Pro358Ser variant also presented with Leber congenital amaurosis (LCA) associated with sensorineural hearing loss (SNHL). Similar cellular phenotype was also observed in patient-derived respiratory epithelial cells.

PMID:39115449 reported eight patients with PCD, of which one patient was identified with a de novo variant in TUBB4B gene. This patient presented with airways disease and hearing loss.

The PCD phenotype has not yet been reported in OMIM, while LCA phenotype is already associated with TUBB4B in OMIM (MIM #617879).
Sources: Literature
Respiratory ciliopathies including non-CF bronchiectasis v3.25 TUBB4B Achchuthan Shanmugasundram Classified gene: TUBB4B as Amber List (moderate evidence)
Respiratory ciliopathies including non-CF bronchiectasis v3.25 TUBB4B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (>10 unrelated cases and functional work) for the promotion of this gene to green rating on the next GMS update.
Respiratory ciliopathies including non-CF bronchiectasis v3.25 TUBB4B Achchuthan Shanmugasundram Gene: tubb4b has been classified as Amber List (Moderate Evidence).
Respiratory ciliopathies including non-CF bronchiectasis v3.24 TUBB4B Achchuthan Shanmugasundram gene: TUBB4B was added
gene: TUBB4B was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: Literature
dd_review, Q1_25_ promote_green tags were added to gene: TUBB4B.
Mode of inheritance for gene: TUBB4B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB4B were set to 38662826; 39115449
Phenotypes for gene: TUBB4B were set to primary ciliary dyskinesia, MONDO:0016575
Review for gene: TUBB4B was set to GREEN
Added comment: PMID:38662826 reported a cohort of 12 patients with primary ciliary dyskinesia (PCD) and with heterozygous variants in TUBB4B gene. Four different variants were reported in these patients. Common clinical features of airway disease including chronic wet cough (7/12), recurrent infections (11/12), bronchiectasis (8/12) and rhinosinusitis (9/12) were observed across the cohort/ 6/12 patients were reported with hydrocephaly. Four patients with the p.Pro358Ser variant also presented with Leber congenital amaurosis (LCA) associated with sensorineural hearing loss (SNHL). Similar cellular phenotype was also observed in patient-derived respiratory epithelial cells.

PMID:39115449 reported eight patients with PCD, of which one patient was identified with a de novo variant in TUBB4B gene.

The PCD phenotype has not yet been reported in OMIM, while LCA phenotype is already associated with TUBB4B in OMIM (MIM #617879).
Sources: Literature
Fetal anomalies v5.7 CACHD1 Achchuthan Shanmugasundram Classified gene: CACHD1 as Amber List (moderate evidence)
Fetal anomalies v5.7 CACHD1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are two fetal cases reported from the same family, although there are six cases from four families reported in total. In addition, there is functional evidence. Hence, this gene can be rated amber with the current evidence.
Fetal anomalies v5.7 CACHD1 Achchuthan Shanmugasundram Gene: cachd1 has been classified as Amber List (Moderate Evidence).
Fetal anomalies v5.6 CACHD1 Achchuthan Shanmugasundram gene: CACHD1 was added
gene: CACHD1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CACHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CACHD1 were set to 38158856
Phenotypes for gene: CACHD1 were set to syndromic complex neurodevelopmental disorder, MONDO:0800439
Review for gene: CACHD1 was set to AMBER
Added comment: PMID:38158856 reported six affected individuals from four unrelated families with biallelic (either homozygous or compound heterozygous) CACHD1 variants (3 splice, 2 frameshift and 1 nonsense variant).

Of these, two cases from the fourth family are fetal cases. Excluding these two fatal cases, all others were affected by syndromic neurodevelopmental abnormalities, multiple organ systems featuring global impairment of psychomotor development, dysmorphic facial features, genitourinary abnormalities, oculo-auricular and congenital malformation. Cognitive impairment was reported to be mild in three cases from three different families, while the fourth case had no cognitive impairment. Psychomotor delay was reported in two unrelated cases and seizure was reported in one.

Facial dysmorphism and ear and genitourinary abnormalities were reported in the two fetal cases, while congenital malformations of the digestive tract was reported in one of them.

Functional evidence from human stem cell-derived neural models and zebrafish mutants are also available in support of the disease association.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Paediatric disorders - additional genes v6.6 CACHD1 Achchuthan Shanmugasundram changed review comment from: PMID:38158856 reported six affected individuals from four unrelated families with biallelic (either him,ozygous or compound heterozygous) CACHD1 variants (3 splice, 2 frameshift and 1 nonsense variant).

Excluding the two fatal cases from the fourth family, all others were affected by syndromic neurodevelopmental abnormalities, multiple organ systems featuring global impairment of psychomotor development, dysmorphic facial features, genitourinary abnormalities, oculo-auricular and congenital malformation. Cognitive impairment was reported to be mild in three cases from three different families, while the fourth case had no cognitive impairment. Psychomotor delay was reported in two unrelated cases and seizure was reported in one.

Functional evidence from human stem cell-derived neural models and zebrafish mutants are also available in support of the disease association.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature; to: PMID:38158856 reported six affected individuals from four unrelated families with biallelic (either homozygous or compound heterozygous) CACHD1 variants (3 splice, 2 frameshift and 1 nonsense variant).

Excluding the two fatal cases from the fourth family, all others were affected by syndromic neurodevelopmental abnormalities, multiple organ systems featuring global impairment of psychomotor development, dysmorphic facial features, genitourinary abnormalities, oculo-auricular and congenital malformation. Cognitive impairment was reported to be mild in three cases from three different families, while the fourth case had no cognitive impairment. Psychomotor delay was reported in two unrelated cases and seizure was reported in one.

Functional evidence from human stem cell-derived neural models and zebrafish mutants are also available in support of the disease association.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Paediatric disorders - additional genes v6.6 CACHD1 Achchuthan Shanmugasundram Classified gene: CACHD1 as Amber List (moderate evidence)
Paediatric disorders - additional genes v6.6 CACHD1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (three unrelated cases and functional studies) for the promotion of this gene to green rating on the next GMS update.
Paediatric disorders - additional genes v6.6 CACHD1 Achchuthan Shanmugasundram Gene: cachd1 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v6.5 CACHD1 Achchuthan Shanmugasundram gene: CACHD1 was added
gene: CACHD1 was added to Paediatric disorders - additional genes. Sources: Literature
Q1_25_ promote_green tags were added to gene: CACHD1.
Mode of inheritance for gene: CACHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CACHD1 were set to 38158856
Phenotypes for gene: CACHD1 were set to syndromic complex neurodevelopmental disorder, MONDO:0800439
Review for gene: CACHD1 was set to GREEN
Added comment: PMID:38158856 reported six affected individuals from four unrelated families with biallelic (either him,ozygous or compound heterozygous) CACHD1 variants (3 splice, 2 frameshift and 1 nonsense variant).

Excluding the two fatal cases from the fourth family, all others were affected by syndromic neurodevelopmental abnormalities, multiple organ systems featuring global impairment of psychomotor development, dysmorphic facial features, genitourinary abnormalities, oculo-auricular and congenital malformation. Cognitive impairment was reported to be mild in three cases from three different families, while the fourth case had no cognitive impairment. Psychomotor delay was reported in two unrelated cases and seizure was reported in one.

Functional evidence from human stem cell-derived neural models and zebrafish mutants are also available in support of the disease association.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Paediatric disorders - additional genes v6.4 PLAG1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Tracy Lester, the phenotypes observed are relevant to R27 Paediatric disorders clinical indication and this gene is present with 'strong' rating on the DD panel of Gene2Phenotype database. As there is sufficient evidence available for green rating, this gene should be promoted to green in the next GMS review.; to: Comment on list classification: As reviewed by Tracy Lester, the phenotypes observed are relevant to R27 Paediatric disorders clinical indication, and this gene is present with 'strong' rating on the DD panel of Gene2Phenotype database. As there is sufficient evidence available for green rating, this gene should be promoted to green in the next GMS review.
Paediatric disorders - additional genes v6.4 PLAG1 Achchuthan Shanmugasundram Classified gene: PLAG1 as Amber List (moderate evidence)
Paediatric disorders - additional genes v6.4 PLAG1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Tracy Lester, the phenotypes observed are relevant to R27 Paediatric disorders clinical indication and this gene is present with 'strong' rating on the DD panel of Gene2Phenotype database. As there is sufficient evidence available for green rating, this gene should be promoted to green in the next GMS review.
Paediatric disorders - additional genes v6.4 PLAG1 Achchuthan Shanmugasundram Gene: plag1 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v6.3 PLAG1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review tag was added to gene: PLAG1.
Tag Q1_25_ promote_green tag was added to gene: PLAG1.
Paediatric disorders - additional genes v6.3 PLAG1 Achchuthan Shanmugasundram reviewed gene: PLAG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28796236, 32546215, 33291420, 37673301; Phenotypes: Silver-Russell syndrome 4, OMIM:618907; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v6.145 FXN_GAA Sarah Leigh Tag STR tag was added to STR: FXN_GAA.
Hereditary neuropathy or pain disorder v6.145 FXN_GAA Sarah Leigh Tag Q3_24_promote_green tag was added to STR: FXN_GAA.
Tag Q3_24_NHS_review tag was added to STR: FXN_GAA.
Hereditary neuropathy or pain disorder v6.145 FXN_GAA Sarah Leigh Classified STR: FXN_GAA as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.145 FXN_GAA Sarah Leigh Str: fxn_gaa has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.144 FXN_GAA Sarah Leigh STR: FXN_GAA was added
STR: FXN_GAA was added to Hereditary neuropathy or pain disorder. Sources: NHS GMS
Mode of inheritance for STR: FXN_GAA was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for STR: FXN_GAA were set to Friedreich ataxia, OMIM:229300; Friedreich ataxia 1, MONDO:0100340
Review for STR: FXN_GAA was set to GREEN
Added comment: This STR has been added to Hereditary neuropathy or pain disorder panel, on the recommendation of James Polke (Rare & Inherited Disease Genomic Laboratory, NHS North Thames GLH). Biallelic (including compound heterozygous) FXN variants, both single nucleotide and repeat expansions, have been associated with Friedreich ataxia, OMIM:229300.
The STR repeat lengths have been reviewed and confirmed by the NHS Genomic Medicine Service.
Sources: NHS GMS
Undiagnosed metabolic disorders v1.624 USF1 Sarah Leigh Tag Q1_25_ demote_amber tag was added to gene: USF1.
Tag Q1_25_ NHS_review tag was added to gene: USF1.
Tag Q1_25_ MOI tag was added to gene: USF1.
Tag Q1_25_ promote_green tag was added to gene: USF1.
Tag Q1_25_ demote_red tag was added to gene: USF1.
Tag Q1_25_ expert_review tag was added to gene: USF1.
Tag Q1_25_ phenotype tag was added to gene: USF1.
Intellectual disability v8.45 TAOK2 Nour Elkhateeb gene: TAOK2 was added
gene: TAOK2 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: TAOK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TAOK2 were set to PMID: 39737487; 29467497
Phenotypes for gene: TAOK2 were set to Developmental delay; Intellectual disability; Speech and language delay; Autism spectrum disorder
Review for gene: TAOK2 was set to GREEN
Added comment: Recent study PMID: 39737487 reporting 10 individuals with varying degrees of Developmental delay, Intellectual disability, Speech and language delay and Autism spectrum disorder as well as other features such as obesity, tall stature and macrocephaly. These individuals had heterozygous missense and truncating TAOK2 variants.
PMID: 29467497 reported individuals with autism and heterozygous missense and truncating TAOK2 variants.
Sources: Literature
Autosomal recessive primary hypertrophic osteoarthropathy v1.12 SLCO2A1 Dmitrijs Rots reviewed gene: SLCO2A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v7.5 SLCO2A1 Dmitrijs Rots reviewed gene: SLCO2A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Structural eye disease v4.1 EFEMP1 Cassandra Smith reviewed gene: EFEMP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34923728, 38083999, 32476818; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Inherited phaeochromocytoma and paraganglioma excluding NF1 v3.1 DNMT3A Dmitrijs Rots gene: DNMT3A was added
gene: DNMT3A was added to Inherited phaeochromocytoma and paraganglioma excluding NF1. Sources: Literature
Mode of inheritance for gene: DNMT3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DNMT3A were set to 39166703
Penetrance for gene: DNMT3A were set to unknown
Mode of pathogenicity for gene: DNMT3A 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: DNMT3A was set to GREEN
Added comment: Over multiple case reports, missense variants in DNMT3A PWWP domain seem to be associated with paragangliomas (PMID:39166703).
Sources: Literature
Renal ciliopathies v3.15 DLG5 Tracy Lester reviewed gene: DLG5: Rating: AMBER; Mode of pathogenicity: None; Publications: 32631816; Phenotypes: CAKUT, hydrocephalus; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Cystic kidney disease v7.10 CFAP47 Achchuthan Shanmugasundram Tag Q4_24_promote_green tag was added to gene: CFAP47.
Cystic kidney disease v7.10 CFAP47 Achchuthan Shanmugasundram Classified gene: CFAP47 as Amber List (moderate evidence)
Cystic kidney disease v7.10 CFAP47 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (three unrelated cases and functional work) for the promotion of this gene to green rating in the next GMS update.
Cystic kidney disease v7.10 CFAP47 Achchuthan Shanmugasundram Gene: cfap47 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v7.9 CFAP47 Achchuthan Shanmugasundram Phenotypes for gene: CFAP47 were changed from PKD to polycystic kidney disease, MONDO:0020642
Cystic kidney disease v7.8 CFAP47 Achchuthan Shanmugasundram Publications for gene: CFAP47 were set to PMID: 38633811
Cystic kidney disease v7.7 CFAP47 Achchuthan Shanmugasundram reviewed gene: CFAP47: Rating: GREEN; Mode of pathogenicity: None; Publications: 39698362; Phenotypes: polycystic kidney disease, MONDO:0020642; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Congenital myopathy v5.12 MB Achchuthan Shanmugasundram Classified gene: MB as Red List (low evidence)
Congenital myopathy v5.12 MB Achchuthan Shanmugasundram Gene: mb has been classified as Red List (Low Evidence).
Congenital myopathy v5.11 MB Achchuthan Shanmugasundram Classified gene: MB as Amber List (moderate evidence)
Congenital myopathy v5.11 MB Achchuthan Shanmugasundram Added comment: Comment on list classification: As the disease onset is typically during adulthood, this gene should be rated red with current evidence.
Congenital myopathy v5.11 MB Achchuthan Shanmugasundram Gene: mb has been classified as Amber List (Moderate Evidence).
Congenital myopathy v5.10 MB Achchuthan Shanmugasundram Phenotypes for gene: MB were changed from to Myopathy, sarcoplasmic body, OMIM:620286
Congenital myopathy v5.9 MB Achchuthan Shanmugasundram Mode of inheritance for gene: MB was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital myopathy v5.8 MB Achchuthan Shanmugasundram reviewed gene: MB: Rating: RED; Mode of pathogenicity: None; Publications: 30918256, 34679218, 35527200; Phenotypes: Myopathy, sarcoplasmic body, OMIM:620286; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital myopathy v5.8 MYMX Achchuthan Shanmugasundram Classified gene: MYMX as Amber List (moderate evidence)
Congenital myopathy v5.8 MYMX Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (three unrelated cases and functional work) for the association of biallelic MYMX variants with congenital myopathy. Hence, this gene can be promoted to green rating in the next GMS update.
Congenital myopathy v5.8 MYMX Achchuthan Shanmugasundram Gene: mymx has been classified as Amber List (Moderate Evidence).
Congenital myopathy v5.7 MYMX Achchuthan Shanmugasundram Phenotypes for gene: MYMX were changed from congenital myopathy with recognizable facial palsy, growth restriction, and dysmorphism to ?Carey-Fineman-Ziter syndrome 2, OMIM:619941
Congenital myopathy v5.6 MYMX Achchuthan Shanmugasundram Publications for gene: MYMX were set to PMID: 39668186
Congenital myopathy v5.5 MYMX Achchuthan Shanmugasundram Mode of inheritance for gene: MYMX was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Congenital myopathy v5.4 MYMX Achchuthan Shanmugasundram Tag Q4_24_promote_green tag was added to gene: MYMX.
Congenital myopathy v5.4 MYMX Achchuthan Shanmugasundram reviewed gene: MYMX: Rating: GREEN; Mode of pathogenicity: None; Publications: 35642635, 39668186; Phenotypes: ?Carey-Fineman-Ziter syndrome 2, OMIM:619941; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.45 PABPC1 Achchuthan Shanmugasundram Tag dd_review tag was added to gene: PABPC1.
Hereditary neuropathy or pain disorder v6.143 PIGG Achchuthan Shanmugasundram Classified gene: PIGG as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.143 PIGG Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Christopher Record, there are six unrelated families reported with biallelic PIGG variants and hereditary motor neuropathy. Hence, this gene can be promoted to green rating in the next GMS review.
Hereditary neuropathy or pain disorder v6.143 PIGG Achchuthan Shanmugasundram Gene: pigg has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.142 PIGG Achchuthan Shanmugasundram Phenotypes for gene: PIGG were changed from HMN to Neurodevelopmental disorder with or without hypotonia, seizures, and cerebellar atrophy, OMIM:616917; childhood-onset motor neuropathy
Hereditary neuropathy or pain disorder v6.141 PIGG Achchuthan Shanmugasundram Tag Q4_24_NHS_review tag was added to gene: PIGG.
Tag Q4_24_promote_green tag was added to gene: PIGG.
Hereditary neuropathy or pain disorder v6.141 PIGG Achchuthan Shanmugasundram reviewed gene: PIGG: Rating: GREEN; Mode of pathogenicity: None; Publications: 39444079; Phenotypes: Neurodevelopmental disorder with or without hypotonia, seizures, and cerebellar atrophy, OMIM:616917, childhood-onset motor neuropathy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v7.18 PABPC1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: PMID:35511136 reported 4 unrelated individuals with de novo PABPC1 variants and with a phenotype of global developmental delay including intellectual disability, movement coordination disorders, seizures, behavioral disorders and mild facial dysmorphisms. There are no biallelic cases reported so far. Hence, the MOI should be updated to "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted" in the next GMS review.
Early onset or syndromic epilepsy v7.18 PABPC1 Achchuthan Shanmugasundram Mode of inheritance for gene: PABPC1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v7.17 PABPC1 Achchuthan Shanmugasundram Tag Q4_24_MOI tag was added to gene: PABPC1.
Early onset or syndromic epilepsy v7.17 PABPC1 Achchuthan Shanmugasundram reviewed gene: PABPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35511136; Phenotypes: neurodevelopmental disorder, MONDO:0700092, epilepsy, MONDO:0005027; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v8.45 PABPC1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: PMID:35511136 reported 4 unrelated individuals with de novo PABPC1 variants and with a phenotype of global developmental delay including intellectual disability, movement coordination disorders, seizures, behavioral disorders and mild facial dysmorphisms. There are no biallelic cases reported so far. Hence, the MOI should be updated to "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted" in the next GMS review.
Intellectual disability v8.45 PABPC1 Achchuthan Shanmugasundram Mode of inheritance for gene: PABPC1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v8.44 PABPC1 Achchuthan Shanmugasundram Tag Q4_24_MOI tag was added to gene: PABPC1.
Intellectual disability v8.44 PABPC1 Achchuthan Shanmugasundram edited their review of gene: PABPC1: Changed phenotypes to: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071
Intellectual disability v8.44 PABPC1 Achchuthan Shanmugasundram reviewed gene: PABPC1: Rating: GREEN; Mode of pathogenicity: None; Publications: 35511136; Phenotypes: neuronevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v7.1 SAG Cassandra Smith reviewed gene: SAG: Rating: GREEN; Mode of pathogenicity: Other; Publications: 28549094, 33047631; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v8.44 REEP2 Achchuthan Shanmugasundram Classified gene: REEP2 as Red List (low evidence)
Intellectual disability v8.44 REEP2 Achchuthan Shanmugasundram Gene: reep2 has been classified as Red List (Low Evidence).
Intellectual disability v8.44 REEP2 Achchuthan Shanmugasundram Classified gene: REEP2 as Red List (low evidence)
Intellectual disability v8.44 REEP2 Achchuthan Shanmugasundram Gene: reep2 has been classified as Red List (Low Evidence).
Early onset or syndromic epilepsy v7.17 CRELD1 Sarah Leigh Tag Q4_24_NHS_review tag was added to gene: CRELD1.
Tag Q4_24_MOI tag was added to gene: CRELD1.
Early onset or syndromic epilepsy v7.17 CRELD1 Sarah Leigh Added comment: Comment on mode of inheritance: The mode of inheritance for CRELD1 on this panel should be changed from "BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal" to "BIALLELIC, autosomal or pseudoautosomal".
Early onset or syndromic epilepsy v7.17 CRELD1 Sarah Leigh Mode of inheritance for gene: CRELD1 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Early onset or syndromic epilepsy v7.16 CRELD1 Sarah Leigh edited their review of gene: CRELD1: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v7.16 CRELD1 Sarah Leigh Phenotypes for gene: CRELD1 were changed from effries-Lakhani neurodevelopmental syndrome, OMIM:620771; Jeffries-Lakhani neurodevelopmental syndrome, MONDO:0958329 to Jeffries-Lakhani neurodevelopmental syndrome, OMIM:620771; Jeffries-Lakhani neurodevelopmental syndrome, MONDO:0958329
Early onset or syndromic epilepsy v7.15 CRELD1 Sarah Leigh Added comment: Comment on phenotypes: Monoallelic variants are associated with Atrioventricular septal defect, partial, with heterotaxy syndrome, OMIM:606217;{Atrioventricular septal defect, susceptibility to, 2}, OMIM:606217;atrioventricular septal defect, susceptibility to, 2, MONDO:0011650. However, this condition is not relevant to Early onset or syndromic epilepsy panel.
Early onset or syndromic epilepsy v7.15 CRELD1 Sarah Leigh Phenotypes for gene: CRELD1 were changed from Atrioventricular septal defect, partial, with heterotaxy syndrome, OMIM:606217; {Atrioventricular septal defect, susceptibility to, 2}, OMIM:606217; atrioventricular septal defect, susceptibility to, 2, MONDO:0011650 to effries-Lakhani neurodevelopmental syndrome, OMIM:620771; Jeffries-Lakhani neurodevelopmental syndrome, MONDO:0958329
Early onset or syndromic epilepsy v7.14 CRELD1 Sarah Leigh edited their review of gene: CRELD1: Added comment: Biallelic CRELD1 variants have been associated with Jeffries-Lakhani neurodevelopmental syndrome (OMIM:620771) and it is a moderate G2P gene for CRELD1-related neurodevelopmental disorder with hypotonia and seizures. At least four CRELD1 variants have been reported in at least 14 patients from 10 unrelated families (PMID: 37947183).; Changed publications to: 37947183
Early onset or syndromic epilepsy v7.14 CRELD1 Sarah Leigh Publications for gene: CRELD1 were set to 32437232
Monogenic hearing loss v4.64 MYO1A Sarah Leigh commented on gene: MYO1A
Monogenic hearing loss v4.64 MYO1A Sarah Leigh Tag curated_removed tag was added to gene: MYO1A.
Monogenic hearing loss v4.64 MYO1A Sarah Leigh Classified gene: MYO1A as No list
Monogenic hearing loss v4.64 MYO1A Sarah Leigh Gene: myo1a has been removed from the panel.
Monogenic hearing loss v4.63 MYO1A Sarah Leigh Publications for gene: MYO1A were set to
Iron metabolism disorders - NOT common HFE mutations v2.12 CYBRD1 Sarah Leigh Tag Q4_24_expert_review tag was added to gene: CYBRD1.
Tag Q4_24_demote_red tag was added to gene: CYBRD1.
Iron metabolism disorders - NOT common HFE mutations v2.12 CYBRD1 Sarah Leigh edited their review of gene: CYBRD1: Changed rating: RED
Iron metabolism disorders - NOT common HFE mutations v2.12 CYBRD1 Sarah Leigh changed review comment from: It would appear that there are no CYBRD1 rare SNVs associated with iron metabolism.  However, PMID: 37632052 concludes that the coexistence of minor alleles of HDAC3 rs976552 and CYBRD1 rs884409 is linked with higher prevalence of hepatocellular carcinoma.

Furthermore, HFE p.C282Y variant together with the CYBRD1 polymorphism rs884409 reduces CYBRD1 promoter activity by 30% (PMID: 19673882).; to: It would appear that there are no CYBRD1 rare SNVs associated with iron metabolism.  However, PMID: 37632052 concludes that the coexistence of minor alleles of HDAC3 rs976552 and CYBRD1 rs884409 is linked with higher prevalence of hepatocellular carcinoma.

Furthermore, HFE p.C282Y variant together with the CYBRD1 polymorphism rs884409 reduces CYBRD1 promoter activity by 30% (PMID: 19673882).

Overall, there is insufficient evidence for CYBRD1 to be green on PanelApp.
Likely inborn error of metabolism v7.9 TTC37 Sarah Leigh edited their review of gene: TTC37: Added comment: There is enough evidence for TTC37 to be Green on the Likely inborn error of metabolism panel and it was also suggested Emma Ashton on behalf of the London North GLH, for GMS Metabolic Consensus Specialist Test Group (2019).; Changed rating: GREEN
Likely inborn error of metabolism v7.9 TTC37 Sarah Leigh Deleted their comment
Iron metabolism disorders - NOT common HFE mutations v2.12 FTH1 Sarah Leigh Tag Q4_24_promote_green tag was added to gene: FTH1.
Iron metabolism disorders - NOT common HFE mutations v2.12 FTH1 Sarah Leigh Phenotypes for gene: FTH1 were changed from ?Hemochromatosis, type 5 OMIM:615517; hemochromatosis type 5 MONDO:0014225 to Neurodegeneration with brain iron accumulation 9, OMIM:620669; ?Hemochromatosis, type 5 OMIM:615517; hemochromatosis type 5 MONDO:0014225
Iron metabolism disorders - NOT common HFE mutations v2.11 FTH1 Sarah Leigh reviewed gene: FTH1: Rating: GREEN; Mode of pathogenicity: None; Publications: 37660254, 37265023; Phenotypes: Neurodegeneration with brain iron accumulation 9, OMIM:620669; Mode of inheritance: None
Iron metabolism disorders - NOT common HFE mutations v2.11 FTH1 Sarah Leigh Classified gene: FTH1 as Amber List (moderate evidence)
Iron metabolism disorders - NOT common HFE mutations v2.11 FTH1 Sarah Leigh Gene: fth1 has been classified as Amber List (Moderate Evidence).
Iron metabolism disorders - NOT common HFE mutations v2.10 FTH1 Sarah Leigh Publications for gene: FTH1 were set to 11389486; 37660254; 37265023
Iron metabolism disorders - NOT common HFE mutations v2.9 FTH1 Sarah Leigh Publications for gene: FTH1 were set to 11389486
Hereditary ataxia with onset in adulthood v7.6 GDAP2 Sarah Leigh Tag Q4_24_NHS_review tag was added to gene: GDAP2.
Tag Q4_24_promote_green tag was added to gene: GDAP2.
Hereditary ataxia with onset in adulthood v7.6 GDAP2 Sarah Leigh changed review comment from: Biallelic GDAP2 variants have been associated with Spinocerebellar ataxia, autosomal recessive 27 (OMIM:618369), but this gene has not been associated with a phenotype in G2P. At least seven variants have been reported in at least six unrelated cases of OMIM:618369 (PMID: 30084953;32437512;32428220;37070050;38587696).; to: Biallelic GDAP2 variants have been associated with Spinocerebellar ataxia, autosomal recessive 27 (OMIM:618369), but this gene has not been associated with a phenotype in G2P. At least seven variants have been reported in at least six unrelated cases of OMIM:618369 (PMID: 30084953;32437512;32428220;37070050;38587696). The Gdap2 knockdown of Drosophila model resulted in shortened lifespan and motor anomalies that resembled the human phenotype (PMID: 30084953). In vitro expression levels of variants: p.Gln316*, p.His400fs*15 and p.Ser436fs*3 transcripts were reduced in comparison to wild type, resulting in barely detectable levels of variant protein. The transcripts of the remaining variants (p.Thr442fs*7 and
p.Arg253*) tested resulted in truncated proteins (PMID: 32437512).
Hereditary ataxia with onset in adulthood v7.6 GDAP2 Sarah Leigh reviewed gene: GDAP2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary ataxia with onset in adulthood v7.6 GDAP2 Sarah Leigh Phenotypes for gene: GDAP2 were changed from Autosomal recessive spinocerebellar ataxia to Spinocerebellar ataxia, autosomal recessive 27, OMIM:618369; spinocerebellar ataxia, autosomal recessive 27, MONDO:0032706
Hereditary ataxia with onset in adulthood v7.5 GDAP2 Sarah Leigh Publications for gene: GDAP2 were set to 30084953; 32437512; 32428220; 37070050
Hereditary ataxia with onset in adulthood v7.4 GDAP2 Sarah Leigh Publications for gene: GDAP2 were set to 30084953; 32437512
Hereditary ataxia with onset in adulthood v7.3 GDAP2 Sarah Leigh Publications for gene: GDAP2 were set to
Ataxia and cerebellar anomalies - narrow panel v7.8 EXOSC5 Sarah Leigh Publications for gene: EXOSC5 were set to 32504085; 29302074
Fetal anomalies v5.5 EXOSC5 Sarah Leigh reviewed gene: EXOSC5: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Fetal anomalies v5.5 EXOSC5 Sarah Leigh Publications for gene: EXOSC5 were set to 32504085; 29302074; 34089229; 30950035
Ataxia and cerebellar anomalies - narrow panel v7.7 EXOSC5 Sarah Leigh Tag Q4_24_NHS_review tag was added to gene: EXOSC5.
Tag Q4_24_promote_green tag was added to gene: EXOSC5.
Ataxia and cerebellar anomalies - narrow panel v7.7 EXOSC5 Sarah Leigh reviewed gene: EXOSC5: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v5.4 EXOSC5 Sarah Leigh Publications for gene: EXOSC5 were set to 32504085; 29302074; 34089229; 30950035
Early onset or syndromic epilepsy v7.13 CRELD1 Tracy Lester reviewed gene: CRELD1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v5.3 EXOSC5 Sarah Leigh Publications for gene: EXOSC5 were set to 32504085; 29302074
Congenital myopathy v5.4 MYMX Dmitrijs Rots gene: MYMX was added
gene: MYMX was added to Congenital myopathy. Sources: Literature
Mode of inheritance for gene: MYMX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYMX were set to PMID: 39668186
Phenotypes for gene: MYMX were set to congenital myopathy with recognizable facial palsy, growth restriction, and dysmorphism
Penetrance for gene: MYMX were set to Complete
Review for gene: MYMX was set to GREEN
Added comment: The PMID: 39668186 describes additional 2 (to previous 2; total 4) patients with congenital myopathy with recognizable facial palsy, growth restriction, and dysmorphism. Enough evidence for the green rating. Probably the gene should be added also to the short stature panel?
Sources: Literature
Cytopenia - NOT Fanconi anaemia v3.36 RPL26 Dmitrijs Rots reviewed gene: RPL26: Rating: GREEN; Mode of pathogenicity: None; Publications: 39268718; Phenotypes: Diamond-Blackfan anemia; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cytopenia - NOT Fanconi anaemia v3.36 RPL17 Dmitrijs Rots gene: RPL17 was added
gene: RPL17 was added to Cytopenia - NOT Fanconi anaemia. Sources: Literature
Mode of inheritance for gene: RPL17 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: RPL17 were set to 39088281
Phenotypes for gene: RPL17 were set to Diamond-Blackfan anemia
Penetrance for gene: RPL17 were set to Incomplete
Review for gene: RPL17 was set to GREEN
Added comment: PMID: 39088281 described 2 families with Diamond-Blackfan anemia & functional data. Enough evidence for the green rating.
probably gene should be added also to other panels (like limb disorders; hematological malignancies).
Sources: Literature
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 BVES Achchuthan Shanmugasundram commented on gene: BVES: The new-gene-name tag was added as the HGNC approved gene name is POPDC1.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 BVES Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: BVES.
Possible mitochondrial disorder - nuclear genes v3.113 ATP5E Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: ATP5E.
Thoracic aortic aneurysm or dissection (GMS) v3.19 PMEPA1 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: PMEPA1.
Intellectual disability v8.43 ARHGAP35 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: ARHGAP35.
Hypogonadotropic hypogonadism (GMS) v3.22 ARHGAP35 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: ARHGAP35.
Fetal anomalies v5.2 RRAS Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: RRAS.
Cytopenia - NOT Fanconi anaemia v3.36 RRAS Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: RRAS.
Osteogenesis imperfecta v4.9 WNT11 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: WNT11.
Mosaic skin disorders - deep sequencing v2.49 GJA4 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: GJA4.
Segmental overgrowth disorders - Deep sequencing v3.19 GJA4 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: GJA4.
Mosaic skin disorders - deep sequencing v2.49 ARAF Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: ARAF.
Segmental overgrowth disorders - Deep sequencing v3.19 ARAF Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: ARAF.
Hereditary neuropathy or pain disorder v6.141 HPDL Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: HPDL.
Optic neuropathy v4.40 DNAJC30 Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: DNAJC30.
Monogenic hearing loss v4.62 KIAA1024L Achchuthan Shanmugasundram Tag gene-checked tag was added to gene: KIAA1024L.
Mosaic skin disorders - deep sequencing v2.49 MAP3K3 Achchuthan Shanmugasundram Tag gene-checked was removed from gene: MAP3K3.
Bleeding and platelet disorders v3.13 TPM4 Achchuthan Shanmugasundram Tag gene-checked was removed from gene: TPM4.
Bleeding and platelet disorders v3.13 TPM4 Achchuthan Shanmugasundram Phenotypes for gene: TPM4 were changed from to Bleeding disorder, platelet-type, 25, OMIM:620486
Cytopenia - NOT Fanconi anaemia v3.36 CXCR2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CXCR2.
Tag Q4_23_NHS_review was removed from gene: CXCR2.
Hypogonadotropic hypogonadism (GMS) v3.22 ARHGAP35 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ARHGAP35.
Tag Q4_23_NHS_review was removed from gene: ARHGAP35.
Intellectual disability v8.43 WBP4 Achchuthan Shanmugasundram Tag Q4_22_promote_green was removed from gene: WBP4.
Tag Q4_24_promote_green tag was added to gene: WBP4.
Monogenic short stature v1.1 SMC5 Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: SMC5.
Tag Q3_24_promote_green tag was added to gene: SMC5.
Monogenic short stature v1.1 SLF2 Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: SLF2.
Tag Q3_24_promote_green tag was added to gene: SLF2.
Monogenic short stature v1.1 RECQL4 Achchuthan Shanmugasundram Tag Q1_24_promote_green was removed from gene: RECQL4.
Tag Q1_24_NHS_review was removed from gene: RECQL4.
Tag Q3_24_promote_green tag was added to gene: RECQL4.
Tag Q3_24_NHS_review tag was added to gene: RECQL4.
Possible mitochondrial disorder - nuclear genes v3.113 MSTO1 Achchuthan Shanmugasundram Tag Q1_24_MOI was removed from gene: MSTO1.
Monogenic short stature v1.1 MSTO1 Achchuthan Shanmugasundram Tag Q1_24_MOI was removed from gene: MSTO1.
Tag Q1_24_NHS_review was removed from gene: MSTO1.
Tag Q3_24_NHS_review tag was added to gene: MSTO1.
Tag Q3_24_MOI tag was added to gene: MSTO1.
Monogenic short stature v1.1 PAPPA2 Achchuthan Shanmugasundram Tag Q1_24_promote_green was removed from gene: PAPPA2.
Tag Q1_24_NHS_review was removed from gene: PAPPA2.
Tag Q1_24_expert_review was removed from gene: PAPPA2.
Tag Q3_24_promote_green tag was added to gene: PAPPA2.
Tag Q3_24_NHS_review tag was added to gene: PAPPA2.
Tag Q3_24_expert_review tag was added to gene: PAPPA2.
Hypertrophic cardiomyopathy v4.20 MT-TI Eleanor Williams Publications for gene: MT-TI were set to 12767666; 21945886; 23332932; 29481798; 30025578
Hypertrophic cardiomyopathy v4.19 MT-TI Eleanor Williams edited their review of gene: MT-TI: Added comment: PMID: 39639347 Lopes et al 2024 - Used the bioinformatics pipeline, MitoHPC, to call mtDNA variants in 1363 genomes of cardiomyopathy patients from the 100,000 genomes project. 4 patients, all with a diagnosis of hypertrophic cardiomyopathy (HCM), with no previously identified genetic cause, had the m.4300A>G variant identified (0.6% of HCM cases without a diagnosis). No individuals from the control group were found to have this variant.; Changed publications to: 39639347
Cholestasis v3.6 RINT1 Zornitza Stark reviewed gene: RINT1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hypertrophic cardiomyopathy v4.19 TULP3 Eleanor Williams Tag Q2_23_promote_green was removed from gene: TULP3.
Tag Q2_23_NHS_review was removed from gene: TULP3.
Hypertrophic cardiomyopathy v4.19 RPS6KB1 Eleanor Williams Tag Q4_22_promote_green was removed from gene: RPS6KB1.
Hypertrophic cardiomyopathy v4.19 RPS6KB1 Eleanor Williams changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. The reviewers felt there was not yet sufficient evidence for a gene-disease association and there is a 'limited' rating for this association in ClinGen (as of 13-Sept-2023.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. The reviewers felt there was not yet sufficient evidence for a gene-disease association and there is a 'limited' rating for this association in ClinGen (as of 13-Sept-2023).
Hypertrophic cardiomyopathy v4.19 TBX20 Eleanor Williams Tag Q2_24_promote_green was removed from gene: TBX20.
Hypertrophic cardiomyopathy v4.19 MT-TI Eleanor Williams Tag Q2_24_promote_green was removed from gene: MT-TI.
Hypertrophic cardiomyopathy v4.19 TULP3 Eleanor Williams commented on gene: TULP3
Hypertrophic cardiomyopathy v4.19 RPS6KB1 Eleanor Williams commented on gene: RPS6KB1
Hypertrophic cardiomyopathy v4.19 TBX20 Eleanor Williams reviewed gene: TBX20: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hypertrophic cardiomyopathy v4.19 MT-TI Eleanor Williams reviewed gene: MT-TI: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MITOCHONDRIAL
Hypertrophic cardiomyopathy v4.18 TBX20 Eleanor Williams Source Expert Review Green was added to TBX20.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hypertrophic cardiomyopathy v4.18 MT-TI Eleanor Williams Source NHS GMS was added to MT-TI.
Source Expert Review Green was added to MT-TI.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v6.5 EYA4 Dmitrijs Rots reviewed gene: EYA4: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Dilated Cardiomyopathy and conduction defects v1.94 EYA4 Dmitrijs Rots reviewed gene: EYA4: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Familial hypoparathyroidism v2.17 TBX1 Eleanor Williams Tag Q1_23_promote_green was removed from gene: TBX1.
Familial hypoparathyroidism v2.17 STX16 Eleanor Williams Tag Q4_22_promote_green was removed from gene: STX16.
Familial hypoparathyroidism v2.17 TBX1 Eleanor Williams reviewed gene: TBX1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Familial hypoparathyroidism v2.17 STX16 Eleanor Williams reviewed gene: STX16: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Familial hypoparathyroidism v2.16 TBX1 Eleanor Williams Source Expert Review Green was added to TBX1.
Source NHS GMS was added to TBX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Familial hypoparathyroidism v2.16 STX16 Eleanor Williams Source Expert Review Green was added to STX16.
Source NHS GMS was added to STX16.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ehlers Danlos syndrome with a likely monogenic cause v3.21 LTBP2 Eleanor Williams Tag Q4_23_promote_green was removed from gene: LTBP2.
Ehlers Danlos syndrome with a likely monogenic cause v3.21 EFEMP1 Eleanor Williams Phenotypes for gene: EFEMP1 were changed from Connective tissue disorder to Cutis laxa, autosomal recessive, type ID, OMIM:620780; cutis laxa, MONDO:0016175
Ehlers Danlos syndrome with a likely monogenic cause v3.20 EFEMP1 Eleanor Williams Tag Q1_24_promote_green was removed from gene: EFEMP1.
Ehlers Danlos syndrome with a likely monogenic cause v3.20 LTBP2 Eleanor Williams reviewed gene: LTBP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ehlers Danlos syndrome with a likely monogenic cause v3.20 EFEMP1 Eleanor Williams reviewed gene: EFEMP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ehlers Danlos syndrome with a likely monogenic cause v3.19 LTBP2 Eleanor Williams Source Expert Review Green was added to LTBP2.
Source NHS GMS was added to LTBP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ehlers Danlos syndrome with a likely monogenic cause v3.19 EFEMP1 Eleanor Williams Source Expert Review Green was added to EFEMP1.
Source NHS GMS was added to EFEMP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ectodermal dysplasia v3.35 KRT86 Eleanor Williams Tag Q4_23_promote_green was removed from gene: KRT86.
Tag Q4_23_NHS_review was removed from gene: KRT86.
Paroxysmal central nervous system disorders v3.12 RHOBTB2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: RHOBTB2.
Paroxysmal central nervous system disorders v3.12 ALPK1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ALPK1.
Tag Q3_23_MOI was removed from gene: ALPK1.
Ectodermal dysplasia v3.35 SREBF1 Eleanor Williams Tag Q4_22_promote_green was removed from gene: SREBF1.
Paroxysmal central nervous system disorders v3.12 RHOBTB2 Achchuthan Shanmugasundram reviewed gene: RHOBTB2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Paroxysmal central nervous system disorders v3.12 ALPK1 Achchuthan Shanmugasundram reviewed gene: ALPK1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ectodermal dysplasia v3.35 RIPK4 Eleanor Williams Tag Q1_23_promote_green was removed from gene: RIPK4.
Ectodermal dysplasia v3.35 PPP1R13L Eleanor Williams Tag Q4_23_promote_green was removed from gene: PPP1R13L.
Ectodermal dysplasia v3.35 LRP6 Eleanor Williams Tag Q3_23_promote_green was removed from gene: LRP6.
Paroxysmal central nervous system disorders v3.11 RHOBTB2 Achchuthan Shanmugasundram Source NHS GMS was added to RHOBTB2.
Source Expert Review Green was added to RHOBTB2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paroxysmal central nervous system disorders v3.11 ALPK1 Achchuthan Shanmugasundram Source NHS GMS was added to ALPK1.
Source Expert Review Green was added to ALPK1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ectodermal dysplasia v3.35 LEF1 Eleanor Williams Tag Q1_24_promote_green was removed from gene: LEF1.
Ectodermal dysplasia v3.35 KRT81 Eleanor Williams Tag Q4_23_promote_green was removed from gene: KRT81.
Tag Q4_23_NHS_review was removed from gene: KRT81.
Ectodermal dysplasia v3.35 SREBF1 Eleanor Williams reviewed gene: SREBF1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ectodermal dysplasia v3.35 RIPK4 Eleanor Williams reviewed gene: RIPK4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ectodermal dysplasia v3.35 PPP1R13L Eleanor Williams reviewed gene: PPP1R13L: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ectodermal dysplasia v3.35 LRP6 Eleanor Williams reviewed gene: LRP6: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ectodermal dysplasia v3.35 LEF1 Eleanor Williams reviewed gene: LEF1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ectodermal dysplasia v3.35 KRT86 Eleanor Williams reviewed gene: KRT86: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ectodermal dysplasia v3.35 KRT81 Eleanor Williams reviewed gene: KRT81: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Ectodermal dysplasia v3.34 SREBF1 Eleanor Williams Source Expert Review Green was added to SREBF1.
Source NHS GMS was added to SREBF1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ectodermal dysplasia v3.34 RIPK4 Eleanor Williams Source Expert Review Green was added to RIPK4.
Source NHS GMS was added to RIPK4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ectodermal dysplasia v3.34 PPP1R13L Eleanor Williams Source Expert Review Green was added to PPP1R13L.
Source NHS GMS was added to PPP1R13L.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ectodermal dysplasia v3.34 LRP6 Eleanor Williams Source Expert Review Green was added to LRP6.
Source NHS GMS was added to LRP6.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ectodermal dysplasia v3.34 LEF1 Eleanor Williams Source Expert Review Green was added to LEF1.
Source NHS GMS was added to LEF1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ectodermal dysplasia v3.34 KRT86 Eleanor Williams Source Expert Review Green was added to KRT86.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ectodermal dysplasia v3.34 KRT81 Eleanor Williams Source Expert Review Green was added to KRT81.
Source NHS GMS was added to KRT81.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Palmoplantar keratodermas v3.27 TGM5 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: TGM5.
Tag Q4_23_NHS_review was removed from gene: TGM5.
Palmoplantar keratodermas v3.27 SERPINB8 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SERPINB8.
Tag Q4_23_NHS_review was removed from gene: SERPINB8.
Palmoplantar keratodermas v3.27 PEX7 Achchuthan Shanmugasundram Tag Q1_24_demote_red was removed from gene: PEX7.
Palmoplantar keratodermas v3.27 PERP Achchuthan Shanmugasundram Tag Q4_22_promote_green was removed from gene: PERP.
Palmoplantar keratodermas v3.27 JUP Achchuthan Shanmugasundram Tag Q4_22_MOI was removed from gene: JUP.
Palmoplantar keratodermas v3.27 FLG2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: FLG2.
Tag Q4_23_NHS_review was removed from gene: FLG2.
Palmoplantar keratodermas v3.27 SLC27A4 Achchuthan Shanmugasundram Tag Q1_24_demote_red was removed from gene: SLC27A4.
Tag Q1_24_expert_review was removed from gene: SLC27A4.
Palmoplantar keratodermas v3.27 POMP Achchuthan Shanmugasundram changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains green. The GMS reviewers note that R165 proposal for this gene is to change to green and R165/166 are often requested together, so it is contradictory to have green/red in these panels.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains green.

The GMS reviewers note that R165 proposal for this gene is to change to green and R165/166 are often requested together, so it is contradictory to have green/red in these panels.
Palmoplantar keratodermas v3.27 POMP Achchuthan Shanmugasundram Tag Q1_24_demote_red was removed from gene: POMP.
Tag Q1_24_expert_review was removed from gene: POMP.
Palmoplantar keratodermas v3.27 PHYH Achchuthan Shanmugasundram Tag Q1_24_demote_red was removed from gene: PHYH.
Tag Q1_24_expert_review was removed from gene: PHYH.
Palmoplantar keratodermas v3.27 MVK Achchuthan Shanmugasundram Tag Q1_24_demote_red was removed from gene: MVK.
Tag Q1_24_expert_review was removed from gene: MVK.
Palmoplantar keratodermas v3.27 CLDN1 Achchuthan Shanmugasundram Tag Q1_24_demote_red was removed from gene: CLDN1.
Tag Q1_24_expert_review was removed from gene: CLDN1.
Palmoplantar keratodermas v3.27 CASP14 Achchuthan Shanmugasundram Tag Q1_24_demote_red was removed from gene: CASP14.
Tag Q1_24_expert_review was removed from gene: CASP14.
Palmoplantar keratodermas v3.27 POMP Achchuthan Shanmugasundram commented on gene: POMP
Palmoplantar keratodermas v3.27 TGM5 Achchuthan Shanmugasundram reviewed gene: TGM5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Palmoplantar keratodermas v3.27 SLC27A4 Achchuthan Shanmugasundram reviewed gene: SLC27A4: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Palmoplantar keratodermas v3.27 SERPINB8 Achchuthan Shanmugasundram reviewed gene: SERPINB8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Palmoplantar keratodermas v3.27 PHYH Achchuthan Shanmugasundram reviewed gene: PHYH: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Palmoplantar keratodermas v3.27 PEX7 Achchuthan Shanmugasundram reviewed gene: PEX7: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Palmoplantar keratodermas v3.27 PERP Achchuthan Shanmugasundram commented on gene: PERP: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Palmoplantar keratodermas v3.27 MVK Achchuthan Shanmugasundram reviewed gene: MVK: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Palmoplantar keratodermas v3.27 JUP Achchuthan Shanmugasundram reviewed gene: JUP: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Palmoplantar keratodermas v3.27 FLG2 Achchuthan Shanmugasundram reviewed gene: FLG2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Palmoplantar keratodermas v3.27 CLDN1 Achchuthan Shanmugasundram reviewed gene: CLDN1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Palmoplantar keratodermas v3.27 CASP14 Achchuthan Shanmugasundram reviewed gene: CASP14: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Palmoplantar keratodermas v3.26 TGM5 Achchuthan Shanmugasundram Source Expert Review Green was added to TGM5.
Source NHS GMS was added to TGM5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Palmoplantar keratodermas v3.26 SLC27A4 Achchuthan Shanmugasundram Source Expert Review Red was added to SLC27A4.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Palmoplantar keratodermas v3.26 SERPINB8 Achchuthan Shanmugasundram Source Expert Review Green was added to SERPINB8.
Source NHS GMS was added to SERPINB8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Palmoplantar keratodermas v3.26 PHYH Achchuthan Shanmugasundram Source Expert Review Red was added to PHYH.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Palmoplantar keratodermas v3.26 PEX7 Achchuthan Shanmugasundram Source Expert Review Red was added to PEX7.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Palmoplantar keratodermas v3.26 PERP Achchuthan Shanmugasundram Source Expert Review Green was added to PERP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Palmoplantar keratodermas v3.26 MVK Achchuthan Shanmugasundram Source Expert Review Red was added to MVK.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Palmoplantar keratodermas v3.26 JUP Achchuthan Shanmugasundram Mode of inheritance for gene JUP was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Palmoplantar keratodermas v3.26 FLG2 Achchuthan Shanmugasundram Source Expert Review Green was added to FLG2.
Source NHS GMS was added to FLG2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Palmoplantar keratodermas v3.26 CLDN1 Achchuthan Shanmugasundram Source Expert Review Red was added to CLDN1.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Palmoplantar keratodermas v3.26 CASP14 Achchuthan Shanmugasundram Source Expert Review Red was added to CASP14.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Cytopenia - NOT Fanconi anaemia v3.36 RRAS Eleanor Williams Tag Q2_24_promote_green was removed from gene: RRAS.
Cytopenia - NOT Fanconi anaemia v3.36 RRAS 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.
Cytopenia - NOT Fanconi anaemia v3.36 RAP1B Eleanor Williams Tag Q4_23_promote_green was removed from gene: RAP1B.
Tag Q4_23_NHS_review was removed from gene: RAP1B.
Cytopenia - NOT Fanconi anaemia v3.36 RAP1B Eleanor Williams changed review comment from: The rating of this gene has been updated togreen and the mode of inheritance set to MONOALLELIC, 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 imprintedfollowing NHS Genomic Medicine Service approval.
Cytopenia - NOT Fanconi anaemia v3.36 DUT Eleanor Williams Tag Q4_23_promote_green was removed from gene: DUT.
Cytopenia - NOT Fanconi anaemia v3.36 RRAS Eleanor Williams reviewed gene: RRAS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cytopenia - NOT Fanconi anaemia v3.36 RAP1B Eleanor Williams reviewed gene: RAP1B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cytopenia - NOT Fanconi anaemia v3.36 DUT Eleanor Williams reviewed gene: DUT: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cytopenia - NOT Fanconi anaemia v3.36 CXCR2 Eleanor Williams reviewed gene: CXCR2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cytopenia - NOT Fanconi anaemia v3.35 RRAS Eleanor Williams Source Expert Review Green was added to RRAS.
Source NHS GMS was added to RRAS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v3.35 RAP1B Eleanor Williams Source Expert Review Green was added to RAP1B.
Source NHS GMS was added to RAP1B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v3.35 DUT Eleanor Williams Source Expert Review Green was added to DUT.
Source NHS GMS was added to DUT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cytopenia - NOT Fanconi anaemia v3.35 CXCR2 Eleanor Williams Source Expert Review Green was added to CXCR2.
Source NHS GMS was added to CXCR2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric pseudo-obstruction syndrome v1.7 MYL9 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: MYL9.
Paediatric pseudo-obstruction syndrome v1.7 MYL9 Achchuthan Shanmugasundram edited their review of gene: MYL9: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Paediatric pseudo-obstruction syndrome v1.6 MYL9 Achchuthan Shanmugasundram Source NHS GMS was added to MYL9.
Source Expert Review Green was added to MYL9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Osteogenesis imperfecta v4.9 WNT11 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: WNT11.
Osteogenesis imperfecta v4.9 WNT11 Achchuthan Shanmugasundram commented on gene: WNT11: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Osteogenesis imperfecta v4.8 WNT11 Achchuthan Shanmugasundram Source NHS GMS was added to WNT11.
Source Expert Review Green was added to WNT11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Corneal dystrophy v3.12 LTBP2 Eleanor Williams Tag Q4_23_promote_green was removed from gene: LTBP2.
Corneal dystrophy v3.12 LTBP2 Eleanor Williams reviewed gene: LTBP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Corneal dystrophy v3.11 LTBP2 Eleanor Williams Source NHS GMS was added to LTBP2.
Source Expert Review Green was added to LTBP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v4.40 UCHL1 Achchuthan Shanmugasundram Tag Q3_23_MOI was removed from gene: UCHL1.
Optic neuropathy v4.40 PDXK Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: PDXK.
Optic neuropathy v4.40 MAG Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: MAG.
Optic neuropathy v4.40 LHX2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: LHX2.
Optic neuropathy v4.40 LETM1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: LETM1.
Optic neuropathy v4.40 HSD17B10 Achchuthan Shanmugasundram Tag Q1_24_promote_green was removed from gene: HSD17B10.
Optic neuropathy v4.40 HK1 Achchuthan Shanmugasundram Tag Q4_22_promote_green was removed from gene: HK1.
Optic neuropathy v4.40 HIKESHI Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: HIKESHI.
Tag Q3_23_NHS_review was removed from gene: HIKESHI.
Optic neuropathy v4.40 BTD Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: BTD.
Optic neuropathy v4.40 UCHL1 Achchuthan Shanmugasundram reviewed gene: UCHL1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic neuropathy v4.40 PDXK Achchuthan Shanmugasundram commented on gene: PDXK: 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.
Optic neuropathy v4.40 MAG Achchuthan Shanmugasundram reviewed gene: MAG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v4.40 LHX2 Achchuthan Shanmugasundram reviewed gene: LHX2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Optic neuropathy v4.40 LETM1 Achchuthan Shanmugasundram reviewed gene: LETM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v4.40 HSD17B10 Achchuthan Shanmugasundram reviewed gene: HSD17B10: Rating: GREEN; 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)
Optic neuropathy v4.40 HK1 Achchuthan Shanmugasundram reviewed gene: HK1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Optic neuropathy v4.40 HIKESHI Achchuthan Shanmugasundram edited their review of gene: HIKESHI: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v4.40 BTD Achchuthan Shanmugasundram commented on gene: BTD: 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.
Optic neuropathy v4.39 UCHL1 Achchuthan Shanmugasundram Source NHS GMS was added to UCHL1.
Mode of inheritance for gene UCHL1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Optic neuropathy v4.39 PDXK Achchuthan Shanmugasundram Source NHS GMS was added to PDXK.
Source Expert Review Green was added to PDXK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v4.39 MAG Achchuthan Shanmugasundram Source Expert Review Green was added to MAG.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v4.39 LHX2 Achchuthan Shanmugasundram Source NHS GMS was added to LHX2.
Source Expert Review Green was added to LHX2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v4.39 LETM1 Achchuthan Shanmugasundram Source NHS GMS was added to LETM1.
Source Expert Review Green was added to LETM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v4.39 HSD17B10 Achchuthan Shanmugasundram Source NHS GMS was added to HSD17B10.
Source Expert Review Green was added to HSD17B10.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v4.39 HK1 Achchuthan Shanmugasundram Source NHS GMS was added to HK1.
Source Expert Review Green was added to HK1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Optic neuropathy v4.39 HIKESHI Achchuthan Shanmugasundram 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)
Optic neuropathy v4.39 BTD Achchuthan Shanmugasundram Source NHS GMS was added to BTD.
Source Expert Review Green was added to BTD.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Congenital myopathy v5.4 VWA1 Arina Puzriakova Tag Q1_24_promote_green was removed from gene: VWA1.
Tag Q1_24_expert_review was removed from gene: VWA1.
Congenital myopathy v5.4 VWA1 Arina Puzriakova reviewed gene: VWA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital myopathy v5.3 VWA1 Arina Puzriakova Source NHS GMS was added to VWA1.
Source Expert Review Green was added to VWA1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Congenital myaesthenic syndrome v4.11 TOR1AIP1 Arina Puzriakova Tag Q4_22_promote_green was removed from gene: TOR1AIP1.
Congenital myaesthenic syndrome v4.11 TOR1AIP1 Arina Puzriakova commented on gene: TOR1AIP1: The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Congenital myaesthenic syndrome v4.10 TOR1AIP1 Arina Puzriakova Source Expert Review Green was added to TOR1AIP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Neuronal ceroid lipofuscinosis v2.8 GRN Achchuthan Shanmugasundram Tag Q4_22_promote_green was removed from gene: GRN.
Neuronal ceroid lipofuscinosis v2.8 GRN Achchuthan Shanmugasundram reviewed gene: GRN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Neuronal ceroid lipofuscinosis v2.7 GRN Achchuthan Shanmugasundram Source Expert Review Green was added to GRN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Congenital muscular dystrophy v5.3 MSTO1 Arina Puzriakova Tag Q1_24_MOI was removed from gene: MSTO1.
Congenital muscular dystrophy v5.3 MSTO1 Arina Puzriakova reviewed gene: MSTO1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric or syndromic cardiomyopathy v6.5 MYZAP Eleanor Williams commented on gene: MYZAP: Copied this gene from R132 Dilated and arrhythmogenic cardiomyopathy since NHS GMS reviewers suggest that it is more suited to be on the R135 Paediatric or syndromic cardiomyopathy panel.

Note the MYZAP gene is part of the GRINL1A complex transcription unit, or GCOM1 gene, which also includes the downstream POLR2M gene.

Helio et al. (2021) (PMID: 34899865) - 2 Finnish families with different homozygous variants in GCOM1 in affected individuals. Probands had either DCM or arrhythmogenic right ventricular cardiomyopathy (ARVC). Note in Family 1, one family member without the variant had DCM secondary to lymphocytic myocarditis. Age at diagnosis ranged from 24 to 41.

Maver et al. (2022) (PMID: 35840178) - 2 Slovenian brothers affected by severe DCM with onset at ages 14 and 16 years. Both had a homozygous premature termination variant in MYZAP.

Ochoa et al. (2024) (PMID: 38436102) - 2 sisters of Spanish ancestry with compound heterozygous variants in MYZAP and a severe form of DCM. Neither patient had extracardiac features. Both were diagnosed in their early 30s.
Congenital muscular dystrophy v5.2 MSTO1 Arina Puzriakova Mode of inheritance for gene MSTO1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Nephrocalcinosis or nephrolithiasis v4.19 WDR72 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: WDR72.
Tag Q1_23_NHS_review was removed from gene: WDR72.
Nephrocalcinosis or nephrolithiasis v4.19 CLCNKB Achchuthan Shanmugasundram Tag Q3_23_MOI was removed from gene: CLCNKB.
Nephrocalcinosis or nephrolithiasis v4.19 WDR72 Achchuthan Shanmugasundram reviewed gene: WDR72: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Nephrocalcinosis or nephrolithiasis v4.19 CLCNKB Achchuthan Shanmugasundram reviewed gene: CLCNKB: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital hypothyroidism v2.20 GNAS Arina Puzriakova Tag Q4_22_MOI was removed from gene: GNAS.
Nephrocalcinosis or nephrolithiasis v4.18 WDR72 Achchuthan Shanmugasundram Source NHS GMS was added to WDR72.
Source Expert Review Green was added to WDR72.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Nephrocalcinosis or nephrolithiasis v4.18 CLCNKB Achchuthan Shanmugasundram Source NHS GMS was added to CLCNKB.
Mode of inheritance for gene CLCNKB was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Congenital hypothyroidism v2.20 GNAS Arina Puzriakova reviewed gene: GNAS: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Congenital hypothyroidism v2.19 GNAS Arina Puzriakova Source NHS GMS was added to GNAS.
Mode of inheritance for gene GNAS was changed from MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mosaic skin disorders - deep sequencing v2.49 TEK Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: TEK.
Tag Q3_23_NHS_review was removed from gene: TEK.
Congenital fibrosis of the extraocular muscles v1.18 MYF5 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: MYF5.
Tag Q4_23_NHS_review was removed from gene: MYF5.
Mosaic skin disorders - deep sequencing v2.49 PTCH1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PTCH1.
Tag Q3_23_NHS_review was removed from gene: PTCH1.
Congenital fibrosis of the extraocular muscles v1.18 COL25A1 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: COL25A1.
Mosaic skin disorders - deep sequencing v2.49 PIK3R1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PIK3R1.
Tag Q3_23_NHS_review was removed from gene: PIK3R1.
Mosaic skin disorders - deep sequencing v2.49 NEK9 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: NEK9.
Tag Q3_23_NHS_review was removed from gene: NEK9.
Congenital fibrosis of the extraocular muscles v1.18 MYF5 Arina Puzriakova reviewed gene: MYF5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital fibrosis of the extraocular muscles v1.18 COL25A1 Arina Puzriakova reviewed gene: COL25A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mosaic skin disorders - deep sequencing v2.49 MVD Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: MVD.
Congenital fibrosis of the extraocular muscles v1.17 MYF5 Arina Puzriakova Source NHS GMS was added to MYF5.
Source Expert Review Green was added to MYF5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Congenital fibrosis of the extraocular muscles v1.17 COL25A1 Arina Puzriakova Source NHS GMS was added to COL25A1.
Source Expert Review Green was added to COL25A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mosaic skin disorders - deep sequencing v2.49 IKBKG Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: IKBKG.
Mosaic skin disorders - deep sequencing v2.49 GJA4 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: GJA4.
Tag Q3_23_NHS_review was removed from gene: GJA4.
Mosaic skin disorders - deep sequencing v2.49 FGFR2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: FGFR2.
Tag Q3_23_NHS_review was removed from gene: FGFR2.
Mosaic skin disorders - deep sequencing v2.49 ATP2A2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ATP2A2.
Tag Q3_23_NHS_review was removed from gene: ATP2A2.
Mosaic skin disorders - deep sequencing v2.49 AKT3 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: AKT3.
Tag Q3_23_NHS_review was removed from gene: AKT3.
Mosaic skin disorders - deep sequencing v2.49 TEK Achchuthan Shanmugasundram reviewed gene: TEK: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mosaic skin disorders - deep sequencing v2.49 PTCH1 Achchuthan Shanmugasundram reviewed gene: PTCH1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mosaic skin disorders - deep sequencing v2.49 PIK3R1 Achchuthan Shanmugasundram reviewed gene: PIK3R1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mosaic skin disorders - deep sequencing v2.49 NEK9 Achchuthan Shanmugasundram reviewed gene: NEK9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mosaic skin disorders - deep sequencing v2.49 MVD Achchuthan Shanmugasundram reviewed gene: MVD: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mosaic skin disorders - deep sequencing v2.49 IKBKG Achchuthan Shanmugasundram reviewed gene: IKBKG: Rating: GREEN; 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)
Mosaic skin disorders - deep sequencing v2.49 GJA4 Achchuthan Shanmugasundram reviewed gene: GJA4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mosaic skin disorders - deep sequencing v2.49 FGFR2 Achchuthan Shanmugasundram reviewed gene: FGFR2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mosaic skin disorders - deep sequencing v2.49 ATP2A2 Achchuthan Shanmugasundram reviewed gene: ATP2A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Mosaic skin disorders - deep sequencing v2.49 AKT3 Achchuthan Shanmugasundram reviewed gene: AKT3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mosaic skin disorders - deep sequencing v2.48 TEK Achchuthan Shanmugasundram Source Expert Review Green was added to TEK.
Source NHS GMS was added to TEK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mosaic skin disorders - deep sequencing v2.48 PTCH1 Achchuthan Shanmugasundram Source Expert Review Green was added to PTCH1.
Source NHS GMS was added to PTCH1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mosaic skin disorders - deep sequencing v2.48 PIK3R1 Achchuthan Shanmugasundram Source Expert Review Green was added to PIK3R1.
Source NHS GMS was added to PIK3R1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mosaic skin disorders - deep sequencing v2.48 NEK9 Achchuthan Shanmugasundram Source Expert Review Green was added to NEK9.
Source NHS GMS was added to NEK9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mosaic skin disorders - deep sequencing v2.48 MVD Achchuthan Shanmugasundram Source Expert Review Green was added to MVD.
Source NHS GMS was added to MVD.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mosaic skin disorders - deep sequencing v2.48 IKBKG Achchuthan Shanmugasundram Source Expert Review Green was added to IKBKG.
Source NHS GMS was added to IKBKG.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mosaic skin disorders - deep sequencing v2.48 GJA4 Achchuthan Shanmugasundram Source Expert Review Green was added to GJA4.
Source NHS GMS was added to GJA4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mosaic skin disorders - deep sequencing v2.48 FGFR2 Achchuthan Shanmugasundram Source Expert Review Green was added to FGFR2.
Source NHS GMS was added to FGFR2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mosaic skin disorders - deep sequencing v2.48 ATP2A2 Achchuthan Shanmugasundram Source Expert Review Green was added to ATP2A2.
Source NHS GMS was added to ATP2A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mosaic skin disorders - deep sequencing v2.48 AKT3 Achchuthan Shanmugasundram Source Expert Review Green was added to AKT3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Congenital adrenal hypoplasia v3.13 CYP11B2 Arina Puzriakova Tag Q1_23_promote_green was removed from gene: CYP11B2.
Congenital adrenal hypoplasia v3.13 CYP11B2 Arina Puzriakova reviewed gene: CYP11B2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital adrenal hypoplasia v3.12 CYP11B2 Arina Puzriakova Source NHS GMS was added to CYP11B2.
Source Expert Review Green was added to CYP11B2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v6.5 MYZAP Eleanor Williams Tag Q2_24_promote_green was removed from gene: MYZAP.
Tag Q4_24_promote_green tag was added to gene: MYZAP.
Paediatric or syndromic cardiomyopathy v6.5 FKRP Eleanor Williams Tag Q4_24_promote_green tag was added to gene: FKRP.
Dilated and arrhythmogenic cardiomyopathy v2.36 MYZAP Eleanor Williams Tag Q2_24_promote_green was removed from gene: MYZAP.
Paediatric or syndromic cardiomyopathy v6.5 MYZAP Eleanor Williams Entity copied from Dilated and arrhythmogenic cardiomyopathy v2.36
Paediatric or syndromic cardiomyopathy v6.5 MYZAP Eleanor Williams gene: MYZAP was added
gene: MYZAP was added to Paediatric or syndromic cardiomyopathy. Sources: Other,Expert Review Amber
Q2_24_promote_green tags were added to gene: MYZAP.
Mode of inheritance for gene: MYZAP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYZAP were set to 34899865; 35840178; 38436102; 20093627; 24698889
Phenotypes for gene: MYZAP were set to Dilated cardiomyopathy, MONDO:0005021; Cardiomyopathy, dilated, 2K, OMIM:620894
Penetrance for gene: MYZAP were set to unknown
Mode of pathogenicity for gene: MYZAP was set to Other
Atypical haemolytic uraemic syndrome v3.6 ADAMTS13 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: ADAMTS13.
Atypical haemolytic uraemic syndrome v3.6 ADAMTS13 Achchuthan Shanmugasundram changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber.

The following is the comment from GMS reviewers:
The testing for associated defects are performed biochemically. The trigger for sequencing of this specific gene is based on clinical MDT and not appropriate as standard practice.
Atypical haemolytic uraemic syndrome v3.6 ADAMTS13 Achchuthan Shanmugasundram changed review comment from: The to_be_confirmed_NHSE tag has been added, as further NHSE review is required before promoting this gene to green.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber.
Membranoproliferative glomerulonephritis including C3 glomerulopathy v3.6 CFI Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: CFI.
Membranoproliferative glomerulonephritis including C3 glomerulopathy v3.6 CFI Achchuthan Shanmugasundram changed review comment from: The to_be_confirmed_NHSE tag has been added, as further NHSE review is required before demoting this gene to amber.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains green.

The following is the comment from GMS reviewers:
The target is included in current screening. Sequence data provides clinically informative information to the NRCTC. An audit of genotype:phenotype correlation is ongoing with in the NRCTC with a completion date in the New Year. We are requesting that this target remains within the panel to enable collation of audit data.
Membranoproliferative glomerulonephritis including C3 glomerulopathy v3.6 CFB Achchuthan Shanmugasundram changed review comment from: The to_be_confirmed_NHSE tag has been added, as further NHSE review is required before demoting this gene to amber.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains green.

The following is the comment from GMS reviewers:
The target is included in current screening. Sequence data provides clinically informative information to the NRCTC. An audit of genotype:phenotype correlation is ongoing with in the NRCTC with a completion date in the New Year. We are requesting that this target remains within the panel to enable collation of audit data.
Childhood solid tumours v4.20 KDM3B Arina Puzriakova Tag Q2_24_promote_green was removed from gene: KDM3B.
Childhood solid tumours v4.20 CDKN2A Arina Puzriakova Tag Q4_23_promote_green was removed from gene: CDKN2A.
Tag Q4_23_NHS_review was removed from gene: CDKN2A.
Childhood solid tumours v4.20 BAP1 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: BAP1.
Tag Q4_23_NHS_review was removed from gene: BAP1.
Childhood solid tumours v4.20 KDM3B Arina Puzriakova reviewed gene: KDM3B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Childhood solid tumours v4.20 CDKN2A Arina Puzriakova edited their review of gene: CDKN2A: 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; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Childhood solid tumours v4.20 BAP1 Arina Puzriakova edited their review of gene: BAP1: 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; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Childhood solid tumours v4.19 KDM3B Arina Puzriakova Source Expert Review Green was added to KDM3B.
Source NHS GMS was added to KDM3B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood solid tumours v4.19 CDKN2A Arina Puzriakova Source Expert Review Green was added to CDKN2A.
Source NHS GMS was added to CDKN2A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood solid tumours v4.19 BAP1 Arina Puzriakova Source Expert Review Green was added to BAP1.
Source NHS GMS was added to BAP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Membranoproliferative glomerulonephritis including C3 glomerulopathy v3.6 CFB Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: CFB.
Cerebral vascular malformations v3.18 COL5A1 Arina Puzriakova Tag Q2_24_promote_green was removed from gene: COL5A1.
Cerebral vascular malformations v3.18 SETD5 Arina Puzriakova Tag watchlist was removed from gene: SETD5.
Tag to_be_confirmed_NHSE was removed from gene: SETD5.
Cerebral vascular malformations v3.18 SETD5 Arina Puzriakova changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remainsAmber. Additional comments from reviewing GLHs: E: I can not find any new published evidence that this gene is associated with Cerebral vascular phenotype since 2020 publication - PMID 31474762 and Helens review in PanelApp. Large cohort study of Moyamoya angiopathy does not identify any individuals with variants in these genes - PMID:37012328. NW: Not enough evidence - limited to one paper only. NEY: moyamoya (the association) seems to be a small part of a developmental disorder phenotype and not a key feature in patients with variants in these genes. They feel more like R27 developmental disorder genes to me. I would keep them as amber. All of the moyamoya diagnoses we have had so far have been in RNF213, which is a pure moyamoya gene.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber.

Additional comments from reviewing GLHs: E: I can not find any new published evidence that this gene is associated with Cerebral vascular phenotype since 2020 publication - PMID 31474762 and Helens review in PanelApp. Large cohort study of Moyamoya angiopathy does not identify any individuals with variants in these genes - PMID:37012328. NW: Not enough evidence - limited to one paper only. NEY: moyamoya (the association) seems to be a small part of a developmental disorder phenotype and not a key feature in patients with variants in these genes. They feel more like R27 developmental disorder genes to me. I would keep them as amber. All of the moyamoya diagnoses we have had so far have been in RNF213, which is a pure moyamoya gene.
Cerebral vascular malformations v3.18 CNOT3 Arina Puzriakova Tag to_be_confirmed_NHSE was removed from gene: CNOT3.
Cerebral vascular malformations v3.18 CNOT3 Arina Puzriakova changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remainsAmber. Additional comments from reviewing GLHs: E: I can not find any new published evidence that this gene is associated with Cerebral vascular phenotype since 2020 publication - PMID 31474762 and Helens review in PanelApp. Large cohort study of Moyamoya angiopathy does not identify any individuals with variants in these genes - PMID:37012328. NW: Not enough evidence - limited to one paper only NEY: moyamoya (the association) seems to be a small part of a developmental disorder phenotype and not a key feature in patients with variants in these genes. They feel more like R27 developmental disorder genes to me. I would keep them as amber. All of the moyamoya diagnoses we have had so far have been in RNF213, which is a pure moyamoya gene.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber.

Additional comments from reviewing GLHs: E: I can not find any new published evidence that this gene is associated with Cerebral vascular phenotype since 2020 publication - PMID 31474762 and Helens review in PanelApp. Large cohort study of Moyamoya angiopathy does not identify any individuals with variants in these genes - PMID:37012328. NW: Not enough evidence - limited to one paper only NEY: moyamoya (the association) seems to be a small part of a developmental disorder phenotype and not a key feature in patients with variants in these genes. They feel more like R27 developmental disorder genes to me. I would keep them as amber. All of the moyamoya diagnoses we have had so far have been in RNF213, which is a pure moyamoya gene.
Cerebral vascular malformations v3.18 CHD4 Arina Puzriakova Tag watchlist was removed from gene: CHD4.
Tag to_be_confirmed_NHSE was removed from gene: CHD4.
Cerebral vascular malformations v3.18 CHD4 Arina Puzriakova changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remainsAmber. Additional comments from reviewing GLHs: E: I can not find any new published evidence that this gene is associated with Cerebral vascular phenotype since 2020 publication - PMID 31474762 and Helens review in PanelApp. Large cohort study of Moyamoya angiopathy does not identify any individuals with variants in these genes - PMID:37012328. NW: Not enough evidence - limited to one paper only. NEY: moyamoya (the association) seems to be a small part of a developmental disorder phenotype and not a key feature in patients with variants in these genes. They feel more like R27 developmental disorder genes to me. I would keep them as amber. All of the moyamoya diagnoses we have had so far have been in RNF213, which is a pure moyamoya gene.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber.

Additional comments from reviewing GLHs: E: I can not find any new published evidence that this gene is associated with Cerebral vascular phenotype since 2020 publication - PMID 31474762 and Helens review in PanelApp. Large cohort study of Moyamoya angiopathy does not identify any individuals with variants in these genes - PMID:37012328. NW: Not enough evidence - limited to one paper only. NEY: moyamoya (the association) seems to be a small part of a developmental disorder phenotype and not a key feature in patients with variants in these genes. They feel more like R27 developmental disorder genes to me. I would keep them as amber. All of the moyamoya diagnoses we have had so far have been in RNF213, which is a pure moyamoya gene.
Cerebral vascular malformations v3.18 COL5A1 Arina Puzriakova reviewed gene: COL5A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral vascular malformations v3.18 SETD5 Arina Puzriakova reviewed gene: SETD5: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral vascular malformations v3.18 CNOT3 Arina Puzriakova reviewed gene: CNOT3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral vascular malformations v3.18 CHD4 Arina Puzriakova reviewed gene: CHD4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral vascular malformations v3.17 COL5A1 Arina Puzriakova Source Expert Review Green was added to COL5A1.
Source NHS GMS was added to COL5A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v6.4 FKRP Eleanor Williams Publications for gene: FKRP were set to
Paediatric or syndromic cardiomyopathy v6.3 FKRP Eleanor Williams commented on gene: FKRP
Dilated and arrhythmogenic cardiomyopathy v2.36 TBX20 Eleanor Williams Tag Q2_24_promote_green was removed from gene: TBX20.
Dilated and arrhythmogenic cardiomyopathy v2.36 TAB2 Eleanor Williams changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. Reviewers note isolated DCM is not the presenting feature, it causes a syndromic phenotpye, and the cardiovascular manifestation is mulitple coronary heart disease and is therefore not suitable for R132 .; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. Reviewers note isolated DCM is not the presenting feature, it causes a syndromic phenotpye, and the cardiovascular manifestation is mulitple coronary heart disease and is therefore not suitable for R132 (where it is already green).
Dilated and arrhythmogenic cardiomyopathy v2.36 TAB2 Eleanor Williams Tag Q3_23_promote_green was removed from gene: TAB2.
Dilated and arrhythmogenic cardiomyopathy v2.36 RRAGC Eleanor Williams Tag Q2_23_promote_green was removed from gene: RRAGC.
Dilated and arrhythmogenic cardiomyopathy v2.36 PRDM16 Eleanor Williams Tag Q2_24_promote_green was removed from gene: PRDM16.
Tag Q2_24_NHS_review was removed from gene: PRDM16.
Dilated and arrhythmogenic cardiomyopathy v2.36 PPA2 Eleanor Williams Tag Q3_23_promote_green was removed from gene: PPA2.
Tag Q3_23_NHS_review was removed from gene: PPA2.
Dilated and arrhythmogenic cardiomyopathy v2.36 MYZAP Eleanor Williams Added comment: Comment on phenotypes: There is now an association with Cardiomyopathy in OMIM so added this as a phenotype term.
Dilated and arrhythmogenic cardiomyopathy v2.36 MYZAP Eleanor Williams Phenotypes for gene: MYZAP were changed from Dilated cardiomyopathy, MONDO:0005021 to Dilated cardiomyopathy, MONDO:0005021; Cardiomyopathy, dilated, 2K, OMIM:620894
Dilated and arrhythmogenic cardiomyopathy v2.35 FKRP Eleanor Williams Tag Q4_23_promote_green was removed from gene: FKRP.
Tag Q4_23_NHS_review was removed from gene: FKRP.
Dilated and arrhythmogenic cardiomyopathy v2.35 TBX20 Eleanor Williams reviewed gene: TBX20: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Dilated and arrhythmogenic cardiomyopathy v2.35 TAB2 Eleanor Williams commented on gene: TAB2
Dilated and arrhythmogenic cardiomyopathy v2.35 RRAGC Eleanor Williams commented on gene: RRAGC
Dilated and arrhythmogenic cardiomyopathy v2.35 PRDM16 Eleanor Williams reviewed gene: PRDM16: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Dilated and arrhythmogenic cardiomyopathy v2.35 PPA2 Eleanor Williams reviewed gene: PPA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Dilated and arrhythmogenic cardiomyopathy v2.35 MYZAP Eleanor Williams commented on gene: MYZAP
Dilated and arrhythmogenic cardiomyopathy v2.35 FKRP Eleanor Williams commented on gene: FKRP
Dilated and arrhythmogenic cardiomyopathy v2.34 TBX20 Eleanor Williams Source Expert Review Green was added to TBX20.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Dilated and arrhythmogenic cardiomyopathy v2.34 PRDM16 Eleanor Williams Source Expert Review Green was added to PRDM16.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Dilated and arrhythmogenic cardiomyopathy v2.34 PPA2 Eleanor Williams Source NHS GMS was added to PPA2.
Source Expert Review Green was added to PPA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hypogonadotropic hypogonadism (GMS) v3.22 SOX11 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: SOX11.
Hypogonadotropic hypogonadism (GMS) v3.22 SOX11 Achchuthan Shanmugasundram 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 green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Hypogonadotropic hypogonadism (GMS) v3.22 PROP1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PROP1.
Hypogonadotropic hypogonadism (GMS) v3.22 CUL4B Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CUL4B.
Hypogonadotropic hypogonadism (GMS) v3.22 ARHGAP35 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated to green and the mode of inheritance updated 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.
Hypogonadotropic hypogonadism (GMS) v3.22 SOX11 Achchuthan Shanmugasundram commented on gene: SOX11: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hypogonadotropic hypogonadism (GMS) v3.22 PROP1 Achchuthan Shanmugasundram commented on gene: PROP1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hypogonadotropic hypogonadism (GMS) v3.22 CUL4B Achchuthan Shanmugasundram commented on gene: CUL4B: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hypogonadotropic hypogonadism (GMS) v3.22 ARHGAP35 Achchuthan Shanmugasundram commented on gene: ARHGAP35: The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Hypogonadotropic hypogonadism (GMS) v3.21 SOX11 Achchuthan Shanmugasundram Source NHS GMS was added to SOX11.
Source Expert Review Green was added to SOX11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hypogonadotropic hypogonadism (GMS) v3.21 PROP1 Achchuthan Shanmugasundram Source Expert Review Green was added to PROP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hypogonadotropic hypogonadism (GMS) v3.21 CUL4B Achchuthan Shanmugasundram Source Expert Review Green was added to CUL4B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hypogonadotropic hypogonadism (GMS) v3.21 ARHGAP35 Achchuthan Shanmugasundram Source NHS GMS was added to ARHGAP35.
Source Expert Review Green was added to ARHGAP35.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hypophosphataemia or rickets v3.6 FAH Achchuthan Shanmugasundram Tag for-review was removed from gene: FAH.
Tag to_be_confirmed_NHSE was removed from gene: FAH.
Hypophosphataemia or rickets v3.6 FAH Achchuthan Shanmugasundram reviewed gene: FAH: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hypophosphataemia or rickets v3.5 FAH Achchuthan Shanmugasundram Source NHS GMS was added to FAH.
Source Expert Review Green was added to FAH.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ichthyosis and erythrokeratoderma v3.30 TGM5 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: TGM5.
Tag Q4_23_NHS_review was removed from gene: TGM5.
Ichthyosis and erythrokeratoderma v3.30 SREBF1 Achchuthan Shanmugasundram Tag Q4_22_promote_green was removed from gene: SREBF1.
Ichthyosis and erythrokeratoderma v3.30 SERPINB8 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SERPINB8.
Tag Q4_23_NHS_review was removed from gene: SERPINB8.
Ichthyosis and erythrokeratoderma v3.30 PERP Achchuthan Shanmugasundram Tag Q4_22_promote_green was removed from gene: PERP.
Ichthyosis and erythrokeratoderma v3.30 CSTA Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CSTA.
Tag Q4_23_NHS_review was removed from gene: CSTA.
Ichthyosis and erythrokeratoderma v3.30 CDSN Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: CDSN.
Tag Q4_23_NHS_review was removed from gene: CDSN.
Ichthyosis and erythrokeratoderma v3.30 ABHD5 Achchuthan Shanmugasundram Tag Q1_24_promote_green was removed from gene: ABHD5.
Tag Q1_24_NHS_review was removed from gene: ABHD5.
Ichthyosis and erythrokeratoderma v3.30 POMP Achchuthan Shanmugasundram Tag Q1_24_promote_green was removed from gene: POMP.
Tag Q1_24_expert_review was removed from gene: POMP.
Ichthyosis and erythrokeratoderma v3.30 TGM5 Achchuthan Shanmugasundram reviewed gene: TGM5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ichthyosis and erythrokeratoderma v3.30 SREBF1 Achchuthan Shanmugasundram commented on gene: SREBF1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Ichthyosis and erythrokeratoderma v3.30 SERPINB8 Achchuthan Shanmugasundram reviewed gene: SERPINB8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ichthyosis and erythrokeratoderma v3.30 POMP Achchuthan Shanmugasundram reviewed gene: POMP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ichthyosis and erythrokeratoderma v3.30 PERP Achchuthan Shanmugasundram commented on gene: PERP: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Ichthyosis and erythrokeratoderma v3.30 CSTA Achchuthan Shanmugasundram reviewed gene: CSTA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ichthyosis and erythrokeratoderma v3.30 CDSN Achchuthan Shanmugasundram reviewed gene: CDSN: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ichthyosis and erythrokeratoderma v3.30 ABHD5 Achchuthan Shanmugasundram reviewed gene: ABHD5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ichthyosis and erythrokeratoderma v3.29 TGM5 Achchuthan Shanmugasundram Source Expert Review Green was added to TGM5.
Source NHS GMS was added to TGM5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ichthyosis and erythrokeratoderma v3.29 SREBF1 Achchuthan Shanmugasundram Source Expert Review Green was added to SREBF1.
Source NHS GMS was added to SREBF1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ichthyosis and erythrokeratoderma v3.29 SERPINB8 Achchuthan Shanmugasundram Source Expert Review Green was added to SERPINB8.
Source NHS GMS was added to SERPINB8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ichthyosis and erythrokeratoderma v3.29 POMP Achchuthan Shanmugasundram Source Expert Review Green was added to POMP.
Source NHS GMS was added to POMP.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Ichthyosis and erythrokeratoderma v3.29 PERP Achchuthan Shanmugasundram Source Expert Review Green was added to PERP.
Source NHS GMS was added to PERP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ichthyosis and erythrokeratoderma v3.29 CSTA Achchuthan Shanmugasundram Source Expert Review Green was added to CSTA.
Source NHS GMS was added to CSTA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ichthyosis and erythrokeratoderma v3.29 CDSN Achchuthan Shanmugasundram Source Expert Review Green was added to CDSN.
Source NHS GMS was added to CDSN.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ichthyosis and erythrokeratoderma v3.29 ABHD5 Achchuthan Shanmugasundram Source Expert Review Green was added to ABHD5.
Source NHS GMS was added to ABHD5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Inherited pancreatic cancer v2.9 STK11 Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: STK11.
Tag Q2_24_NHS_review was removed from gene: STK11.
Inherited pancreatic cancer v2.9 ATM Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: ATM.
Tag Q2_24_MOI was removed from gene: ATM.
Tag Q2_24_NHS_review was removed from gene: ATM.
Inherited pancreatic cancer v2.9 STK11 Achchuthan Shanmugasundram reviewed gene: STK11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Inherited pancreatic cancer v2.9 ATM Achchuthan Shanmugasundram reviewed gene: ATM: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Inherited pancreatic cancer v2.8 STK11 Achchuthan Shanmugasundram Source Expert Review Green was added to STK11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Inherited pancreatic cancer v2.8 ATM Achchuthan Shanmugasundram Source NHS GMS was added to ATM.
Source Expert Review Green was added to ATM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Iron metabolism disorders - NOT common HFE mutations v2.8 STAB1 Achchuthan Shanmugasundram Tag Q1_24_promote_green was removed from gene: STAB1.
Iron metabolism disorders - NOT common HFE mutations v2.8 STAB1 Achchuthan Shanmugasundram commented on gene: STAB1: 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.
Iron metabolism disorders - NOT common HFE mutations v2.7 STAB1 Achchuthan Shanmugasundram Source Expert Review Green was added to STAB1.
Source NHS GMS was added to STAB1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Laterality disorders and isomerism v3.20 DAW1 Achchuthan Shanmugasundram Tag Q4_22_promote_green was removed from gene: DAW1.
Laterality disorders and isomerism v3.20 ARL2BP Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: ARL2BP.
Tag Q2_24_MOI was removed from gene: ARL2BP.
Tag Q2_24_NHS_review was removed from gene: ARL2BP.
Laterality disorders and isomerism v3.20 DAW1 Achchuthan Shanmugasundram edited their review of gene: DAW1: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Laterality disorders and isomerism v3.20 ARL2BP Achchuthan Shanmugasundram reviewed gene: ARL2BP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Laterality disorders and isomerism v3.19 DAW1 Achchuthan Shanmugasundram Source NHS GMS was added to DAW1.
Source Expert Review Green was added to DAW1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Laterality disorders and isomerism v3.19 ARL2BP Achchuthan Shanmugasundram Source NHS GMS was added to ARL2BP.
Source Expert Review Green was added to ARL2BP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v4.62 PTPRQ Achchuthan Shanmugasundram Tag Q3_23_MOI was removed from gene: PTPRQ.
Monogenic hearing loss v4.62 PSMC3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PSMC3.
Monogenic hearing loss v4.62 PLXNB2 Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: PLXNB2.
Monogenic hearing loss v4.62 PKHD1L1 Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: PKHD1L1.
Monogenic hearing loss v4.62 NLRP12 Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: NLRP12.
Monogenic hearing loss v4.62 LETM1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: LETM1.
Monogenic hearing loss v4.62 KIAA1024L Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: KIAA1024L.
Monogenic hearing loss v4.62 GRXCR2 Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: GRXCR2.
Monogenic hearing loss v4.62 GPR156 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: GPR156.
Tag Q3_23_NHS_review was removed from gene: GPR156.
Monogenic hearing loss v4.62 DNAJC3 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: DNAJC3.
Monogenic hearing loss v4.62 CRLS1 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: CRLS1.
Monogenic hearing loss v4.62 ATP2B2 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: ATP2B2.
Tag Q2_23_NHS_review was removed from gene: ATP2B2.
Monogenic hearing loss v4.62 ATP11A Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: ATP11A.
Monogenic hearing loss v4.62 SOX2 Achchuthan Shanmugasundram Tag for-review was removed from gene: SOX2.
Tag to_be_confirmed_NHSE was removed from gene: SOX2.
Monogenic hearing loss v4.62 FOXI1 Achchuthan Shanmugasundram Tag watchlist_moi tag was added to gene: FOXI1.
Monogenic hearing loss v4.62 GJB3 Achchuthan Shanmugasundram Tag for-review was removed from gene: GJB3.
Tag to_be_confirmed_NHSE was removed from gene: GJB3.
Monogenic hearing loss v4.62 FOXI1 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: FOXI1.
Monogenic hearing loss v4.62 FOXI1 Achchuthan Shanmugasundram changed review comment from: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed and remains BIALLELIC, autosomal or pseudoautosomal. The review from North Thames GLH notes that no good recent evidence to support monoallelic/digenic inheritance and suggests keeping under review. The review from North West GLH notes that biallelic inheritance is only applicable to hearing loss in ClinGen / OMIM - fits with KCNJ10 and SLC26A4.; to: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed and remains BIALLELIC, autosomal or pseudoautosomal.

The review from North Thames GLH notes that no good recent evidence to support monoallelic/digenic inheritance and suggests keeping under review.

The review from North West GLH notes that biallelic inheritance is only applicable to hearing loss in ClinGen / OMIM - fits with KCNJ10 and SLC26A4.
Monogenic hearing loss v4.62 COL9A3 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: COL9A3.
Monogenic hearing loss v4.62 FOXI1 Achchuthan Shanmugasundram commented on gene: FOXI1
Monogenic hearing loss v4.62 SOX2 Achchuthan Shanmugasundram reviewed gene: SOX2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v4.62 PTPRQ Achchuthan Shanmugasundram commented on gene: PTPRQ: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Monogenic hearing loss v4.62 PSMC3 Achchuthan Shanmugasundram commented on gene: PSMC3: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Monogenic hearing loss v4.62 PLXNB2 Achchuthan Shanmugasundram commented on gene: PLXNB2: 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.
Monogenic hearing loss v4.62 PKHD1L1 Achchuthan Shanmugasundram commented on gene: PKHD1L1: 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.
Monogenic hearing loss v4.62 NLRP12 Achchuthan Shanmugasundram commented on gene: NLRP12: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Monogenic hearing loss v4.62 LETM1 Achchuthan Shanmugasundram reviewed gene: LETM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v4.62 KIAA1024L Achchuthan Shanmugasundram commented on gene: KIAA1024L: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Monogenic hearing loss v4.62 GRXCR2 Achchuthan Shanmugasundram commented on gene: GRXCR2: 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.
Monogenic hearing loss v4.62 GPR156 Achchuthan Shanmugasundram commented on gene: GPR156: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Monogenic hearing loss v4.62 GJB3 Achchuthan Shanmugasundram reviewed gene: GJB3: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic hearing loss v4.62 DNAJC3 Achchuthan Shanmugasundram commented on gene: DNAJC3: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Monogenic hearing loss v4.62 CRLS1 Achchuthan Shanmugasundram commented on gene: CRLS1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Monogenic hearing loss v4.62 COL9A3 Achchuthan Shanmugasundram reviewed gene: COL9A3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic hearing loss v4.62 ATP2B2 Achchuthan Shanmugasundram reviewed gene: ATP2B2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Monogenic hearing loss v4.62 ATP11A Achchuthan Shanmugasundram commented on gene: ATP11A: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Monogenic hearing loss v4.61 SOX2 Achchuthan Shanmugasundram Source NHS GMS was added to SOX2.
Source Expert Review Amber was added to SOX2.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Monogenic hearing loss v4.61 PTPRQ Achchuthan Shanmugasundram Source NHS GMS was added to PTPRQ.
Mode of inheritance for gene PTPRQ was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Monogenic hearing loss v4.61 PSMC3 Achchuthan Shanmugasundram Source Expert Review Green was added to PSMC3.
Source NHS GMS was added to PSMC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v4.61 PLXNB2 Achchuthan Shanmugasundram Source Expert Review Green was added to PLXNB2.
Source NHS GMS was added to PLXNB2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v4.61 PKHD1L1 Achchuthan Shanmugasundram Source Expert Review Green was added to PKHD1L1.
Source NHS GMS was added to PKHD1L1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v4.61 NLRP12 Achchuthan Shanmugasundram Source Expert Review Green was added to NLRP12.
Source NHS GMS was added to NLRP12.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v4.61 LETM1 Achchuthan Shanmugasundram Source Expert Review Green was added to LETM1.
Source NHS GMS was added to LETM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v4.61 KIAA1024L Achchuthan Shanmugasundram Source Expert Review Green was added to KIAA1024L.
Source NHS GMS was added to KIAA1024L.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v4.61 GRXCR2 Achchuthan Shanmugasundram Source Expert Review Green was added to GRXCR2.
Source NHS GMS was added to GRXCR2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v4.61 GPR156 Achchuthan Shanmugasundram Source Expert Review Green was added to GPR156.
Source NHS GMS was added to GPR156.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v4.61 GJB3 Achchuthan Shanmugasundram Source NHS GMS was added to GJB3.
Source Expert Review Amber was added to GJB3.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Monogenic hearing loss v4.61 DNAJC3 Achchuthan Shanmugasundram Source Expert Review Green was added to DNAJC3.
Source NHS GMS was added to DNAJC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v4.61 CRLS1 Achchuthan Shanmugasundram Source Expert Review Green was added to CRLS1.
Source NHS GMS was added to CRLS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v4.61 COL9A3 Achchuthan Shanmugasundram Source Expert Review Green was added to COL9A3.
Source NHS GMS was added to COL9A3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v4.61 ATP2B2 Achchuthan Shanmugasundram Source Expert Review Green was added to ATP2B2.
Source NHS GMS was added to ATP2B2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic hearing loss v4.61 ATP11A Achchuthan Shanmugasundram Source Expert Review Green was added to ATP11A.
Source NHS GMS was added to ATP11A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic diabetes v2.60 SMPD4 Achchuthan Shanmugasundram Tag Q1_24_promote_green was removed from gene: SMPD4.
Monogenic diabetes v2.60 DUT Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: DUT.
Monogenic diabetes v2.60 SMPD4 Achchuthan Shanmugasundram commented on gene: SMPD4: 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.
Monogenic diabetes v2.60 DUT Achchuthan Shanmugasundram reviewed gene: DUT: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic diabetes v2.59 SMPD4 Achchuthan Shanmugasundram Source Expert Review Green was added to SMPD4.
Source NHS GMS was added to SMPD4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Monogenic diabetes v2.59 DUT Achchuthan Shanmugasundram Source Expert Review Green was added to DUT.
Source NHS GMS was added to DUT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorder with complex V deficiency v2.18 ATP5O Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: ATP5O.
Mitochondrial disorder with complex V deficiency v2.18 ATP5E Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ATP5E.
Mitochondrial disorder with complex V deficiency v2.18 ATP5O Achchuthan Shanmugasundram reviewed gene: ATP5O: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorder with complex V deficiency v2.18 ATP5E Achchuthan Shanmugasundram reviewed gene: ATP5E: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorder with complex V deficiency v2.17 ATP5O Achchuthan Shanmugasundram Source Expert Review Green was added to ATP5O.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorder with complex V deficiency v2.17 ATP5E Achchuthan Shanmugasundram Source Expert Review Green was added to ATP5E.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorder with complex IV deficiency v3.23 COX5A Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: COX5A.
Mitochondrial disorder with complex IV deficiency v3.23 COX11 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: COX11.
Mitochondrial disorder with complex IV deficiency v3.23 COX5A Achchuthan Shanmugasundram reviewed gene: COX5A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorder with complex IV deficiency v3.23 COX11 Achchuthan Shanmugasundram reviewed gene: COX11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Mitochondrial disorder with complex IV deficiency v3.22 COX5A Achchuthan Shanmugasundram Source Expert Review Green was added to COX5A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorder with complex IV deficiency v3.22 COX11 Achchuthan Shanmugasundram Source Expert Review Green was added to COX11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 SMCHD1 Achchuthan Shanmugasundram Tag Q1_24_promote_green was removed from gene: SMCHD1.
Tag Q1_24_NHS_review was removed from gene: SMCHD1.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 PYROXD1 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: PYROXD1.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 POPDC3 Achchuthan Shanmugasundram Tag Q1_24_promote_green was removed from gene: POPDC3.
Tag Q1_24_NHS_review was removed from gene: POPDC3.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 PNPLA2 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: PNPLA2.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 MYH7 Achchuthan Shanmugasundram Tag Q4_22_MOI was removed from gene: MYH7.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 HMGCR Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: HMGCR.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 CAPN3 Achchuthan Shanmugasundram Tag Q2_23_MOI was removed from gene: CAPN3.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 BVES Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: BVES.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 ACTN2 Achchuthan Shanmugasundram Tag watchlist_moi was removed from gene: ACTN2.
Tag Q2_23_promote_green was removed from gene: ACTN2.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 ABHD5 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ABHD5.
Tag Q4_23_NHS_review was removed from gene: ABHD5.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 POGLUT1 Achchuthan Shanmugasundram changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber.

The comment from the GMS reviewers is as follows:
Over the past 3 years, (when we were looking at a slightly larger gene panel (essentially R82 plus 20 genes)) we have screened more than 1000 patients on R82 and for POGLUT1 have not identified any clinically significant variants.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 POGLUT1 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: POGLUT1.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 DPM3 Achchuthan Shanmugasundram Tag Q4_22_promote_green was removed from gene: DPM3.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 DPM3 Achchuthan Shanmugasundram changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber.

The comment from the GMS reviewers is as follows:
Over the past 3 years, (when we were looking at a slightly larger gene panel (essentially R82 plus 20 genes)) we have screened more than 1000 patients on R82 and for DPM3 have not identified any clinically significant variants.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 CASQ1 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: CASQ1.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 CASQ1 Achchuthan Shanmugasundram changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber.

The comment from the GMS reviewers is as follows:
Over the past 3 years, (when we were looking at a slightly larger gene panel (essentially R82 plus 20 genes)) we have screened more than 1000 patients on R82 and for CASQ1 have not identified any clinically significant variants.
Intellectual disability v8.43 WBP4 Sarah Leigh Publications for gene: WBP4 were set to
Intellectual disability v8.42 WBP4 Sarah Leigh Classified gene: WBP4 as Amber List (moderate evidence)
Intellectual disability v8.42 WBP4 Sarah Leigh Gene: wbp4 has been classified as Amber List (Moderate Evidence).
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 CASQ1 Achchuthan Shanmugasundram edited their review of gene: CASQ1: Changed rating: AMBER
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 POGLUT1 Achchuthan Shanmugasundram commented on gene: POGLUT1
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 DPM3 Achchuthan Shanmugasundram commented on gene: DPM3
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 CASQ1 Achchuthan Shanmugasundram commented on gene: CASQ1: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 SMCHD1 Achchuthan Shanmugasundram reviewed gene: SMCHD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 PYROXD1 Achchuthan Shanmugasundram commented on gene: PYROXD1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 POPDC3 Achchuthan Shanmugasundram reviewed gene: POPDC3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 PNPLA2 Achchuthan Shanmugasundram commented on gene: PNPLA2: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 MYH7 Achchuthan Shanmugasundram reviewed gene: MYH7: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 HMGCR Achchuthan Shanmugasundram reviewed gene: HMGCR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 CAPN3 Achchuthan Shanmugasundram edited their review of gene: CAPN3: Added comment: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 BVES Achchuthan Shanmugasundram commented on gene: BVES: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 ACTN2 Achchuthan Shanmugasundram commented on gene: ACTN2: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.40 ABHD5 Achchuthan Shanmugasundram edited their review of gene: ABHD5: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.39 SMCHD1 Achchuthan Shanmugasundram Source Expert Review Green was added to SMCHD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.39 PYROXD1 Achchuthan Shanmugasundram Source NHS GMS was added to PYROXD1.
Source Expert Review Green was added to PYROXD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.39 POPDC3 Achchuthan Shanmugasundram Source NHS GMS was added to POPDC3.
Source Expert Review Green was added to POPDC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.39 PNPLA2 Achchuthan Shanmugasundram Source NHS GMS was added to PNPLA2.
Source Expert Review Green was added to PNPLA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.39 MYH7 Achchuthan Shanmugasundram Mode of inheritance for gene MYH7 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.39 HMGCR Achchuthan Shanmugasundram Source NHS GMS was added to HMGCR.
Source Expert Review Green was added to HMGCR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.39 CAPN3 Achchuthan Shanmugasundram Source NHS GMS was added to CAPN3.
Mode of inheritance for gene CAPN3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.39 BVES Achchuthan Shanmugasundram Source Expert Review Green was added to BVES.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.39 ACTN2 Achchuthan Shanmugasundram Source NHS GMS was added to ACTN2.
Source Expert Review Green was added to ACTN2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.39 ABHD5 Achchuthan Shanmugasundram Source NHS GMS was added to ABHD5.
Source Expert Review Green was added to ABHD5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v8.41 WBP4 Sarah Leigh gene: WBP4 was added
gene: WBP4 was added to Intellectual disability. Sources: Literature
Q4_24_NHS_review, Q4_22_promote_green tags were added to gene: WBP4.
Mode of inheritance for gene: WBP4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WBP4 were set to Neurodevelopemental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalities, OMIM:620852; neurodevelopmental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalities, MONDO:0971043
Review for gene: WBP4 was set to GREEN
Added comment: WBP4 variants have been associated with Neurodevelopemental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalities (OMIM:620852). PMID: 37963460 reports four apparently loss of function WBP4 variants in four unrelated cases.
Sources: Literature
Bleeding and platelet disorders v3.12 BLOC1S5 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: BLOC1S5.
Tag Q4_23_NHS_review was removed from gene: BLOC1S5.
Bleeding and platelet disorders v3.12 ADAMTS13 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: ADAMTS13.
Tag Q4_23_NHS_review was removed from gene: ADAMTS13.
Bleeding and platelet disorders v3.12 BLOC1S5 Arina Puzriakova edited their review of gene: BLOC1S5: 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
Bleeding and platelet disorders v3.12 ADAMTS13 Arina Puzriakova edited their review of gene: ADAMTS13: 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; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bleeding and platelet disorders v3.11 BLOC1S5 Arina Puzriakova Source Expert Review Green was added to BLOC1S5.
Source NHS GMS was added to BLOC1S5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Bleeding and platelet disorders v3.11 ADAMTS13 Arina Puzriakova Source Expert Review Green was added to ADAMTS13.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Amelogenesis imperfecta v3.11 PLXNB2 Arina Puzriakova Tag Q2_24_promote_green was removed from gene: PLXNB2.
Amelogenesis imperfecta v3.11 AMBN Arina Puzriakova Tag Q2_24_MOI was removed from gene: AMBN.
Amelogenesis imperfecta v3.11 PLXNB2 Arina Puzriakova reviewed gene: PLXNB2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Amelogenesis imperfecta v3.11 AMBN Arina Puzriakova reviewed gene: AMBN: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Amelogenesis imperfecta v3.10 PLXNB2 Arina Puzriakova Source Expert Review Green was added to PLXNB2.
Source NHS GMS was added to PLXNB2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Amelogenesis imperfecta v3.10 AMBN Arina Puzriakova Source NHS GMS was added to AMBN.
Mode of inheritance for gene AMBN was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Albinism or congenital nystagmus v3.11 TYR Arina Puzriakova Tag Q4_22_MOI was removed from gene: TYR.
Albinism or congenital nystagmus v3.11 CNGB3 Arina Puzriakova Tag Q4_22_promote_green was removed from gene: CNGB3.
Albinism or congenital nystagmus v3.11 CLDN11 Arina Puzriakova Tag Q4_23_promote_green was removed from gene: CLDN11.
Albinism or congenital nystagmus v3.11 TYR Arina Puzriakova edited their review of gene: TYR: Added comment: The mode of inheritance of this gene has been updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Albinism or congenital nystagmus v3.11 CNGB3 Arina Puzriakova commented on gene: CNGB3: 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.
Albinism or congenital nystagmus v3.11 CLDN11 Arina Puzriakova reviewed gene: CLDN11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Albinism or congenital nystagmus v3.10 TYR Arina Puzriakova Source NHS GMS was added to TYR.
Mode of inheritance for gene TYR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Albinism or congenital nystagmus v3.10 CNGB3 Arina Puzriakova Source NHS GMS was added to CNGB3.
Source Expert Review Green was added to CNGB3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Albinism or congenital nystagmus v3.10 CLDN11 Arina Puzriakova 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)
Acute rhabdomyolysis v1.21 MLIP Arina Puzriakova Tag Q4_22_promote_green was removed from gene: MLIP.
Acute rhabdomyolysis v1.21 PHKB Arina Puzriakova Tag Q3_23_expert_review was removed from gene: PHKB.
Tag Q3_23_demote_red was removed from gene: PHKB.
Acute rhabdomyolysis v1.21 MLIP Arina Puzriakova reviewed gene: MLIP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Acute rhabdomyolysis v1.21 PHKB Arina Puzriakova edited their review of gene: PHKB: Added comment: The rating of this gene has been updated to Red following NHS Genomic Medicine Service approval. Additional comments from reviewing GLHs: NW: In keeping with previous NHS GMS review for equivalent panel. NEY: PHKB which has never had an association with Rhabdomyolysis and so I agree with its removal from the panel.; Changed rating: RED
Acute rhabdomyolysis v1.20 PHKB Arina Puzriakova Source Expert Review Red was added to PHKB.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Acute rhabdomyolysis v1.20 MLIP Arina Puzriakova Source NHS GMS was added to MLIP.
Source Expert Review Green was added to MLIP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal muscle channelopathy v3.5 CNBP_CCTG Achchuthan Shanmugasundram commented on STR: CNBP_CCTG
Skeletal muscle channelopathy v3.5 CNBP_CCTG Achchuthan Shanmugasundram Tag Q1_24_promote_green was removed from STR: CNBP_CCTG.
Hereditary systemic amyloidosis v1.24 NLRP3 Achchuthan Shanmugasundram changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber.

This is the comment from national provider at North Thames GLH: This gene is well known cause of Cryopyrin-associated periodic syndrome (CAPS), a rare hereditary autoinflammatory disorder and is included in R413 autoinflammatory panel. It shouldn't be added to this panel because patients with Muckle-Wells syndrome who are referred with a query autoinflammatory disorder will undergo screening for the R413 autoinflammatory panel and not R204 amyloid panel.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber.

This is the comment from the national provider at North Thames GLH: This gene is well known cause of Cryopyrin-associated periodic syndrome (CAPS), a rare hereditary autoinflammatory disorder and is included in R413 autoinflammatory panel. It shouldn't be added to this panel because patients with Muckle-Wells syndrome who are referred with a query autoinflammatory disorder will undergo screening for the R413 autoinflammatory panel and not R204 amyloid panel.
Hereditary systemic amyloidosis v1.24 NLRP3 Achchuthan Shanmugasundram changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber.

This is the comment from national provider at North Thames GLH: This gene is well known cause of Cryopyrin-associated periodic syndrome (CAPS), a rare hereditary autoinflammatory disorder and is included in R413 autoinflammatory panel. It shouldn't be added to this panel because patients with Muckle-Wells syndrome who are referred with a query autoinflammatory disorder will undergo screening for the R413 autoinflammatory panel and not R204 amyloid panel.
Hereditary systemic amyloidosis v1.24 NLRP3 Achchuthan Shanmugasundram Tag for-review was removed from gene: NLRP3.
Tag to_be_confirmed_NHSE was removed from gene: NLRP3.
Hereditary systemic amyloidosis v1.24 NLRP3 Achchuthan Shanmugasundram commented on gene: NLRP3
Membranoproliferative glomerulonephritis including C3 glomerulopathy v3.6 CFI Achchuthan Shanmugasundram Tag for-review was removed from gene: CFI.
Membranoproliferative glomerulonephritis including C3 glomerulopathy v3.6 CFB Achchuthan Shanmugasundram Tag for-review was removed from gene: CFB.
Membranoproliferative glomerulonephritis including C3 glomerulopathy v3.6 CFI Achchuthan Shanmugasundram commented on gene: CFI
Membranoproliferative glomerulonephritis including C3 glomerulopathy v3.6 CFB Achchuthan Shanmugasundram commented on gene: CFB
Atypical haemolytic uraemic syndrome v3.6 ADAMTS13 Achchuthan Shanmugasundram commented on gene: ADAMTS13
Atypical haemolytic uraemic syndrome v3.5 ADAMTS13 Achchuthan Shanmugasundram Tag for-review was removed from gene: ADAMTS13.
Osteopetrosis v1.35 RASGRP2 Achchuthan Shanmugasundram Tag Q1_24_demote_red was removed from gene: RASGRP2.
Tag Q1_24_expert_review was removed from gene: RASGRP2.
Tag to_be_confirmed_NHSE tag was added to gene: RASGRP2.
Osteopetrosis v1.35 RASGRP2 Achchuthan Shanmugasundram commented on gene: RASGRP2
Congenital hyperinsulinism v3.5 AKT2 Achchuthan Shanmugasundram Deleted their comment
Congenital hyperinsulinism v3.5 GPC3 Achchuthan Shanmugasundram Deleted their comment
Congenital hyperinsulinism v3.5 GPC3 Achchuthan Shanmugasundram commented on gene: GPC3
Congenital hyperinsulinism v3.5 AKT2 Achchuthan Shanmugasundram commented on gene: AKT2
Vascular skin disorders v1.65 FOXC2 Achchuthan Shanmugasundram Tag Q1_24_demote_red was removed from gene: FOXC2.
Tag Q1_24_expert_review was removed from gene: FOXC2.
Tag to_be_confirmed_NHSE tag was added to gene: FOXC2.
Vascular skin disorders v1.65 FOXC2 Achchuthan Shanmugasundram commented on gene: FOXC2
Vascular skin disorders v1.65 FLT4 Achchuthan Shanmugasundram Tag Q1_24_demote_red was removed from gene: FLT4.
Tag Q1_24_expert_review was removed from gene: FLT4.
Tag to_be_confirmed_NHSE tag was added to gene: FLT4.
Vascular skin disorders v1.65 FLT4 Achchuthan Shanmugasundram commented on gene: FLT4
Vascular skin disorders v1.65 CCBE1 Achchuthan Shanmugasundram Tag Q1_24_demote_red was removed from gene: CCBE1.
Tag Q1_24_expert_review was removed from gene: CCBE1.
Tag to_be_confirmed_NHSE tag was added to gene: CCBE1.
Vascular skin disorders v1.65 CCBE1 Achchuthan Shanmugasundram commented on gene: CCBE1
Vascular skin disorders v1.65 STAMBP Achchuthan Shanmugasundram Tag Q1_24_promote_green was removed from gene: STAMBP.
Vascular skin disorders v1.65 AKT3 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: AKT3.
Vascular skin disorders v1.65 STAMBP Achchuthan Shanmugasundram reviewed gene: STAMBP: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Vascular skin disorders v1.65 AKT3 Achchuthan Shanmugasundram reviewed gene: AKT3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Vascular skin disorders v1.64 STAMBP Achchuthan Shanmugasundram Source Expert Review Green was added to STAMBP.
Source NHS GMS was added to STAMBP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Vascular skin disorders v1.64 AKT3 Achchuthan Shanmugasundram Source Expert Review Green was added to AKT3.
Source NHS GMS was added to AKT3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Thoracic aortic aneurysm or dissection (GMS) v3.19 SECISBP2 Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: SECISBP2.
Tag Q2_24_NHS_review was removed from gene: SECISBP2.
Thoracic aortic aneurysm or dissection (GMS) v3.19 PMEPA1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PMEPA1.
Tag Q4_23_NHS_review was removed from gene: PMEPA1.
Thoracic aortic aneurysm or dissection (GMS) v3.19 COL1A1 Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: COL1A1.
Tag Q2_24_expert_review was removed from gene: COL1A1.
Tag Q2_24_NHS_review was removed from gene: COL1A1.
Thoracic aortic aneurysm or dissection (GMS) v3.19 SECISBP2 Achchuthan Shanmugasundram commented on gene: SECISBP2: 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.
Thoracic aortic aneurysm or dissection (GMS) v3.19 PMEPA1 Achchuthan Shanmugasundram reviewed gene: PMEPA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Thoracic aortic aneurysm or dissection (GMS) v3.19 COL1A1 Achchuthan Shanmugasundram reviewed gene: COL1A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Thoracic aortic aneurysm or dissection (GMS) v3.18 SECISBP2 Achchuthan Shanmugasundram Source NHS GMS was added to SECISBP2.
Source Expert Review Green was added to SECISBP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Thoracic aortic aneurysm or dissection (GMS) v3.18 PMEPA1 Achchuthan Shanmugasundram Source NHS GMS was added to PMEPA1.
Source Expert Review Green was added to PMEPA1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Thoracic aortic aneurysm or dissection (GMS) v3.18 COL1A1 Achchuthan Shanmugasundram Source NHS GMS was added to COL1A1.
Source Expert Review Green was added to COL1A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe early-onset obesity v4.12 GNAS Achchuthan Shanmugasundram Tag Q4_22_MOI was removed from gene: GNAS.
Severe early-onset obesity v4.12 DYRK1B Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: DYRK1B.
Tag Q2_23_NHS_review was removed from gene: DYRK1B.
Severe early-onset obesity v4.12 ADCY3 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ADCY3.
Severe early-onset obesity v4.12 GNAS Achchuthan Shanmugasundram reviewed gene: GNAS: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Severe early-onset obesity v4.12 DYRK1B Achchuthan Shanmugasundram edited their review of gene: DYRK1B: 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
Severe early-onset obesity v4.12 ADCY3 Achchuthan Shanmugasundram commented on gene: ADCY3: The rating of this gene has been updated to green and the mode of inheritance set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Severe early-onset obesity v4.11 GNAS Achchuthan Shanmugasundram Source NHS GMS was added to GNAS.
Mode of inheritance for gene GNAS was changed from MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed) to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Severe early-onset obesity v4.11 DYRK1B Achchuthan Shanmugasundram Source Expert Review Green was added to DYRK1B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe early-onset obesity v4.11 ADCY3 Achchuthan Shanmugasundram Source NHS GMS was added to ADCY3.
Source Expert Review Green was added to ADCY3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Segmental overgrowth disorders - Deep sequencing v3.19 PIK3R1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PIK3R1.
Tag Q3_23_NHS_review was removed from gene: PIK3R1.
Segmental overgrowth disorders - Deep sequencing v3.19 GJA4 Achchuthan Shanmugasundram Tag recurrent-variant tag was added to gene: GJA4.
Segmental overgrowth disorders - Deep sequencing v3.19 GJA4 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: GJA4.
Tag recurrent-variant was removed from gene: GJA4.
Segmental overgrowth disorders - Deep sequencing v3.19 ARAF Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: ARAF.
Tag Q3_23_NHS_review was removed from gene: ARAF.
Segmental overgrowth disorders - Deep sequencing v3.19 AKT2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: AKT2.
Tag Q3_23_NHS_review was removed from gene: AKT2.
Segmental overgrowth disorders - Deep sequencing v3.19 PIK3R1 Achchuthan Shanmugasundram reviewed gene: PIK3R1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Segmental overgrowth disorders - Deep sequencing v3.19 GJA4 Achchuthan Shanmugasundram reviewed gene: GJA4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Segmental overgrowth disorders - Deep sequencing v3.19 ARAF Achchuthan Shanmugasundram reviewed gene: ARAF: Rating: GREEN; 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)
Segmental overgrowth disorders - Deep sequencing v3.19 AKT2 Achchuthan Shanmugasundram reviewed gene: AKT2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Segmental overgrowth disorders - Deep sequencing v3.18 PIK3R1 Achchuthan Shanmugasundram Source NHS GMS was added to PIK3R1.
Source Expert Review Green was added to PIK3R1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Segmental overgrowth disorders - Deep sequencing v3.18 GJA4 Achchuthan Shanmugasundram Source NHS GMS was added to GJA4.
Source Expert Review Green was added to GJA4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Segmental overgrowth disorders - Deep sequencing v3.18 ARAF Achchuthan Shanmugasundram Source NHS GMS was added to ARAF.
Source Expert Review Green was added to ARAF.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Segmental overgrowth disorders - Deep sequencing v3.18 AKT2 Achchuthan Shanmugasundram Source NHS GMS was added to AKT2.
Source Expert Review Green was added to AKT2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v3.23 SPEF2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: SPEF2.
Tag Q4_23_NHS_review was removed from gene: SPEF2.
Respiratory ciliopathies including non-CF bronchiectasis v3.23 NME5 Achchuthan Shanmugasundram Tag watchlist was removed from gene: NME5.
Tag Q4_23_promote_green was removed from gene: NME5.
Tag Q4_23_NHS_review was removed from gene: NME5.
Respiratory ciliopathies including non-CF bronchiectasis v3.23 FOXJ1 Achchuthan Shanmugasundram Tag watchlist was removed from gene: FOXJ1.
Tag Q4_23_promote_green was removed from gene: FOXJ1.
Tag Q4_23_NHS_review was removed from gene: FOXJ1.
Respiratory ciliopathies including non-CF bronchiectasis v3.23 DAW1 Achchuthan Shanmugasundram Tag Q4_22_promote_green was removed from gene: DAW1.
Respiratory ciliopathies including non-CF bronchiectasis v3.23 SPEF2 Achchuthan Shanmugasundram edited their review of gene: SPEF2: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Respiratory ciliopathies including non-CF bronchiectasis v3.23 NME5 Achchuthan Shanmugasundram commented on gene: NME5: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Respiratory ciliopathies including non-CF bronchiectasis v3.23 FOXJ1 Achchuthan Shanmugasundram commented on gene: FOXJ1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Respiratory ciliopathies including non-CF bronchiectasis v3.23 DAW1 Achchuthan Shanmugasundram edited their review of gene: DAW1: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Respiratory ciliopathies including non-CF bronchiectasis v3.22 SPEF2 Achchuthan Shanmugasundram Source Expert Review Green was added to SPEF2.
Source NHS GMS was added to SPEF2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v3.22 NME5 Achchuthan Shanmugasundram Source Expert Review Green was added to NME5.
Source NHS GMS was added to NME5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v3.22 FOXJ1 Achchuthan Shanmugasundram Source Expert Review Green was added to FOXJ1.
Source NHS GMS was added to FOXJ1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Respiratory ciliopathies including non-CF bronchiectasis v3.22 DAW1 Achchuthan Shanmugasundram Source Expert Review Green was added to DAW1.
Source NHS GMS was added to DAW1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Renal tubulopathies v4.21 WDR72 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: WDR72.
Renal tubulopathies v4.21 RMND1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: RMND1.
Tag Q3_23_NHS_review was removed from gene: RMND1.
Renal tubulopathies v4.21 WDR72 Achchuthan Shanmugasundram reviewed gene: WDR72: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Renal tubulopathies v4.21 RMND1 Achchuthan Shanmugasundram commented on gene: RMND1: 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.
Renal tubulopathies v4.20 WDR72 Achchuthan Shanmugasundram Source Expert Review Green was added to WDR72.
Source NHS GMS was added to WDR72.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Renal tubulopathies v4.20 RMND1 Achchuthan Shanmugasundram Source Expert Review Green was added to RMND1.
Source NHS GMS was added to RMND1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rare genetic inflammatory skin disorders v3.22 NLRP1 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: NLRP1.
Rare genetic inflammatory skin disorders v3.22 GNB1 Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: GNB1.
Rare genetic inflammatory skin disorders v3.22 NLRP1 Achchuthan Shanmugasundram commented on gene: NLRP1: The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Rare genetic inflammatory skin disorders v3.22 GNB1 Achchuthan Shanmugasundram commented on gene: GNB1: 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.
Rare genetic inflammatory skin disorders v3.21 NLRP1 Achchuthan Shanmugasundram Source Expert Review Green was added to NLRP1.
Source NHS GMS was added to NLRP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rare genetic inflammatory skin disorders v3.21 GNB1 Achchuthan Shanmugasundram Source Expert Review Green was added to GNB1.
Source NHS GMS was added to GNB1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Pulmonary arterial hypertension v3.8 SARS2 Achchuthan Shanmugasundram Tag for-review was removed from gene: SARS2.
Tag to_be_confirmed_NHSE was removed from gene: SARS2.
Pulmonary arterial hypertension v3.8 ABCC8 Achchuthan Shanmugasundram Tag for-review was removed from gene: ABCC8.
Tag to_be_confirmed_NHSE was removed from gene: ABCC8.
Pulmonary arterial hypertension v3.8 SARS2 Achchuthan Shanmugasundram reviewed gene: SARS2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pulmonary arterial hypertension v3.8 ABCC8 Achchuthan Shanmugasundram reviewed gene: ABCC8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Pulmonary arterial hypertension v3.7 SARS2 Achchuthan Shanmugasundram Source Expert Review Green was added to SARS2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Pulmonary arterial hypertension v3.7 ABCC8 Achchuthan Shanmugasundram Source NHS GMS was added to ABCC8.
Source Expert Review Green was added to ABCC8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Proteinuric renal disease v4.22 PRDM15 Achchuthan Shanmugasundram Tag Q2_24_promote_green was removed from gene: PRDM15.
Proteinuric renal disease v4.22 NOS1AP Achchuthan Shanmugasundram Tag Q1_24_promote_green was removed from gene: NOS1AP.
Proteinuric renal disease v4.22 PRDM15 Achchuthan Shanmugasundram commented on gene: PRDM15: 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.
Proteinuric renal disease v4.22 NOS1AP Achchuthan Shanmugasundram commented on gene: NOS1AP: 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.
Proteinuric renal disease v4.21 PRDM15 Achchuthan Shanmugasundram Source Expert Review Green was added to PRDM15.
Source NHS GMS was added to PRDM15.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Proteinuric renal disease v4.21 NOS1AP Achchuthan Shanmugasundram Source Expert Review Green was added to NOS1AP.
Source NHS GMS was added to NOS1AP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary lymphoedema v3.13 ERG Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: ERG.
Tag Q4_23_NHS_review was removed from gene: ERG.
Primary lymphoedema v3.13 ERG Achchuthan Shanmugasundram reviewed gene: ERG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary lymphoedema v3.12 ERG Achchuthan Shanmugasundram Source Expert Review Green was added to ERG.
Source NHS GMS was added to ERG.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v3.113 QARS Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: QARS.
Possible mitochondrial disorder - nuclear genes v3.113 PTCD3 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: PTCD3.
Tag Q4_23_NHS_review was removed from gene: PTCD3.
Possible mitochondrial disorder - nuclear genes v3.113 PPOX Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PPOX.
Possible mitochondrial disorder - nuclear genes v3.113 PANK2 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: PANK2.
Possible mitochondrial disorder - nuclear genes v3.113 OXCT1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: OXCT1.
Possible mitochondrial disorder - nuclear genes v3.113 MRM2 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: MRM2.
Tag Q4_23_NHS_review was removed from gene: MRM2.
Possible mitochondrial disorder - nuclear genes v3.113 LETM1 Achchuthan Shanmugasundram Tag Q3_23_promote_green was removed from gene: LETM1.
Tag Q3_23_NHS_review was removed from gene: LETM1.
Possible mitochondrial disorder - nuclear genes v3.113 IDH3A Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: IDH3A.
Tag Q3_23_NHS_review was removed from gene: IDH3A.
Possible mitochondrial disorder - nuclear genes v3.113 HSPA9 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HSPA9.
Tag Q4_23_NHS_review was removed from gene: HSPA9.
Possible mitochondrial disorder - nuclear genes v3.113 HADHB Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: HADHB.
Possible mitochondrial disorder - nuclear genes v3.113 CYCS Achchuthan Shanmugasundram Tag Q1_24_promote_green was removed from gene: CYCS.
Possible mitochondrial disorder - nuclear genes v3.113 CRLS1 Achchuthan Shanmugasundram Tag Q1_23_promote_green was removed from gene: CRLS1.
Tag Q3_23_NHS_review was removed from gene: CRLS1.
Possible mitochondrial disorder - nuclear genes v3.113 COX5A Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: COX5A.
Tag Q4_23_NHS_review was removed from gene: COX5A.
Possible mitochondrial disorder - nuclear genes v3.113 COX11 Achchuthan Shanmugasundram Tag Q4_23_promote_green was removed from gene: COX11.
Tag Q4_23_NHS_review was removed from gene: COX11.
Possible mitochondrial disorder - nuclear genes v3.113 C2orf69 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: C2orf69.
Tag Q3_23_NHS_review was removed from gene: C2orf69.
Possible mitochondrial disorder - nuclear genes v3.113 ATP5O Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: ATP5O.
Tag Q3_23_NHS_review was removed from gene: ATP5O.
Possible mitochondrial disorder - nuclear genes v3.113 ATP5E Achchuthan Shanmugasundram Tag watchlist was removed from gene: ATP5E.
Tag Q1_24_promote_green was removed from gene: ATP5E.
Tag Q1_24_NHS_review was removed from gene: ATP5E.
Possible mitochondrial disorder - nuclear genes v3.113 HPDL Achchuthan Shanmugasundram Tag for-review was removed from gene: HPDL.
Tag to_be_confirmed_NHSE was removed from gene: HPDL.
Possible mitochondrial disorder - nuclear genes v3.113 QARS Achchuthan Shanmugasundram commented on gene: QARS: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Possible mitochondrial disorder - nuclear genes v3.113 PTCD3 Achchuthan Shanmugasundram reviewed gene: PTCD3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v3.113 PPOX Achchuthan Shanmugasundram commented on gene: PPOX: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Possible mitochondrial disorder - nuclear genes v3.113 PANK2 Achchuthan Shanmugasundram commented on gene: PANK2: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Possible mitochondrial disorder - nuclear genes v3.113 OXCT1 Achchuthan Shanmugasundram commented on gene: OXCT1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Possible mitochondrial disorder - nuclear genes v3.113 MSTO1 Achchuthan Shanmugasundram reviewed gene: MSTO1: Rating: ; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v3.113 MRM2 Achchuthan Shanmugasundram reviewed gene: MRM2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v3.113 LETM1 Achchuthan Shanmugasundram reviewed gene: LETM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v3.113 IDH3A Achchuthan Shanmugasundram reviewed gene: IDH3A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v3.113 HSPA9 Achchuthan Shanmugasundram commented on gene: HSPA9: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Possible mitochondrial disorder - nuclear genes v3.113 HPDL Achchuthan Shanmugasundram reviewed gene: HPDL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v3.113 HADHB Achchuthan Shanmugasundram commented on gene: HADHB: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Possible mitochondrial disorder - nuclear genes v3.113 CYCS Achchuthan Shanmugasundram reviewed gene: CYCS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Possible mitochondrial disorder - nuclear genes v3.113 CRLS1 Achchuthan Shanmugasundram commented on gene: CRLS1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Possible mitochondrial disorder - nuclear genes v3.113 COX5A Achchuthan Shanmugasundram reviewed gene: COX5A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v3.113 COX11 Achchuthan Shanmugasundram reviewed gene: COX11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v3.113 C2orf69 Achchuthan Shanmugasundram edited their review of gene: C2orf69: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v3.113 ATP5O Achchuthan Shanmugasundram reviewed gene: ATP5O: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v3.113 ATP5E Achchuthan Shanmugasundram reviewed gene: ATP5E: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v3.112 QARS Achchuthan Shanmugasundram Source Expert Review Green was added to QARS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v3.112 PTCD3 Achchuthan Shanmugasundram Source Expert Review Green was added to PTCD3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v3.112 PPOX Achchuthan Shanmugasundram Source Expert Review Green was added to PPOX.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v3.112 PANK2 Achchuthan Shanmugasundram Source Expert Review Green was added to PANK2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v3.112 OXCT1 Achchuthan Shanmugasundram Source Expert Review Green was added to OXCT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v3.112 MSTO1 Achchuthan Shanmugasundram Mode of inheritance for gene MSTO1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Possible mitochondrial disorder - nuclear genes v3.112 MRM2 Achchuthan Shanmugasundram Source Expert Review Green was added to MRM2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v3.112 LETM1 Achchuthan Shanmugasundram Source Expert Review Green was added to LETM1.
Source NHS GMS was added to LETM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v3.112 IDH3A Achchuthan Shanmugasundram Source Expert Review Green was added to IDH3A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v3.112 HSPA9 Achchuthan Shanmugasundram Source Expert Review Green was added to HSPA9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v3.112 HPDL Achchuthan Shanmugasundram Source Expert Review Green was added to HPDL.
Source NHS GMS was added to HPDL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v3.112 HADHB Achchuthan Shanmugasundram Source Expert Review Green was added to HADHB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v3.112 CYCS Achchuthan Shanmugasundram Source Expert Review Green was added to CYCS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v3.112 CRLS1 Achchuthan Shanmugasundram Source Expert Review Green was added to CRLS1.
Source NHS GMS was added to CRLS1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v3.112 COX5A Achchuthan Shanmugasundram Source Expert Review Green was added to COX5A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v3.112 COX11 Achchuthan Shanmugasundram Source Expert Review Green was added to COX11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v3.112 C2orf69 Achchuthan Shanmugasundram Source Expert Review Green was added to C2orf69.
Source NHS GMS was added to C2orf69.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v3.112 ATP5O Achchuthan Shanmugasundram Source Expert Review Green was added to ATP5O.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Possible mitochondrial disorder - nuclear genes v3.112 ATP5E Achchuthan Shanmugasundram Source Expert Review Green was added to ATP5E.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Pituitary hormone deficiency v3.14 KCNQ1 Achchuthan Shanmugasundram Tag watchlist was removed from gene: KCNQ1.
Tag Q1_24_promote_green was removed from gene: KCNQ1.
Tag Q1_24_NHS_review was removed from gene: KCNQ1.
Tag Q1_24_expert_review was removed from gene: KCNQ1.
Pituitary hormone deficiency v3.14 KCNQ1 Achchuthan Shanmugasundram commented on gene: KCNQ1: The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Pituitary hormone deficiency v3.13 KCNQ1 Achchuthan Shanmugasundram Source Expert Review Green was added to KCNQ1.
Source NHS GMS was added to KCNQ1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Pigmentary skin disorders v3.14 LMNA Achchuthan Shanmugasundram Tag Q1_24_promote_green was removed from gene: LMNA.
Tag Q1_24_NHS_review was removed from gene: LMNA.
Pigmentary skin disorders v3.14 LMNA Achchuthan Shanmugasundram reviewed gene: LMNA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Pigmentary skin disorders v3.13 LMNA Achchuthan Shanmugasundram Source Expert Review Green was added to LMNA.
Source NHS GMS was added to LMNA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cystic kidney disease v7.7 CFAP47 Dmitrijs Rots gene: CFAP47 was added
gene: CFAP47 was added to Cystic kidney disease. Sources: Literature
Mode of inheritance for gene: CFAP47 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CFAP47 were set to PMID: 38633811
Phenotypes for gene: CFAP47 were set to PKD
Penetrance for gene: CFAP47 were set to unknown
Mode of pathogenicity for gene: CFAP47 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: CFAP47 was set to GREEN
Added comment: Three cases & some functional work described in PMID: 38633811 (now published).
Sources: Literature
Distal myopathies v6.2 NEB Arina Puzriakova Publications for gene: NEB were set to
Congenital myopathy v5.2 NEB Arina Puzriakova Publications for gene: NEB were set to 12207937
Intellectual disability v8.40 CRELD1 Arina Puzriakova Publications for gene: CRELD1 were set to 37947183
Ataxia and cerebellar anomalies - narrow panel v7.7 NAXE Arina Puzriakova Publications for gene: NAXE were set to 27616477; 27122014; 27290639; 30022751; 31758406; 31745726
Ataxia and cerebellar anomalies - narrow panel v7.6 NAXE Arina Puzriakova edited their review of gene: NAXE: Added comment: - PMID: 39455596 - identified a patient with NAXE-related mitochondrial encephalopathy and novel biallelic GGGCC repeat expansion as long as ~200 repeats in the NAXE promoter region using long-read sequencing; Changed publications to: 27616477, 27122014, 27290639, 30022751, 31758406, 31745726, 39455596
Hereditary Erythrocytosis v2.6 JAK2 Anna Godfrey reviewed gene: JAK2: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: PMID: 38629639, 37639050; Phenotypes: Hereditary erythrocytosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Laterality disorders and isomerism v3.18 ARMC4 Eleanor Williams Phenotypes for gene: ARMC4 were changed from Ciliary dyskinesia, primary, 23, 615451 to Ciliary dyskinesia, primary, 23, OMIM:615451
Fetal anomalies v5.2 MYBBP1A Achchuthan Shanmugasundram Phenotypes for gene: MYBBP1A were changed from to non-immune hydrops fetalis, MONDO:0009369
Fetal anomalies v5.1 MYBBP1A Achchuthan Shanmugasundram Tag Q3_24_MOI was removed from gene: MYBBP1A.
Hereditary neuropathy or pain disorder v6.141 LRP12 Sarah Leigh Classified gene: LRP12 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.141 LRP12 Sarah Leigh Gene: lrp12 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.140 LRP12 Sarah Leigh Classified gene: LRP12 as Red List (low evidence)
Hereditary neuropathy or pain disorder v6.140 LRP12 Sarah Leigh Gene: lrp12 has been classified as Red List (Low Evidence).
Hereditary neuropathy or pain disorder v6.139 LRP12 Sarah Leigh edited their review of gene: LRP12: Added comment: Apart from the LRP12_CGG variant, no other LRP12 variants have been associated with conditions in OMIM, G2P or Mondo.; Changed rating: RED
Hereditary neuropathy or pain disorder v6.139 NOTCH2NL Sarah Leigh Classified gene: NOTCH2NL as Red List (low evidence)
Hereditary neuropathy or pain disorder v6.139 NOTCH2NL Sarah Leigh Gene: notch2nl has been classified as Red List (Low Evidence).
Hereditary neuropathy or pain disorder v6.138 NOTCH2NL Sarah Leigh reviewed gene: NOTCH2NL: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Intellectual disability v8.39 KCND1 Sarah Leigh Publications for gene: KCND1 were set to
Hereditary neuropathy or pain disorder v6.138 NDC1 Achchuthan Shanmugasundram Tag Q3_24_MOI was removed from gene: NDC1.
Skeletal dysplasia v7.5 RIPPLY2 Achchuthan Shanmugasundram Mode of inheritance for gene: RIPPLY2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v7.1 MAN2B1 Achchuthan Shanmugasundram Tag Q3_24_MOI was removed from gene: MAN2B1.
Retinal disorders v7.1 DCT Achchuthan Shanmugasundram Tag Q3_24_MOI was removed from gene: DCT.
Intellectual disability v8.38 AFF3_GCC Sarah Leigh edited their review of STR: AFF3_GCC: Added comment: The genomic coordinates of the AFF3_GCC repeat expansion is not available. The number of normal and pathogenic repeats have not been established either.; Changed rating: RED
Intellectual disability v8.38 AFF3_GCC Sarah Leigh Phenotypes for STR: AFF3_GCC were changed from to neurodevelopmental disorder unspecified
Intellectual disability v8.37 AFF3_GCC Sarah Leigh Mode of inheritance for STR: AFF3_GCC was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Retinal disorders v7.1 RP1L1 Achchuthan Shanmugasundram Tag Q2_24_MOI was removed from gene: RP1L1.
Tag Q2_24_expert_review was removed from gene: RP1L1.
Intellectual disability v8.36 ATXN7L3 Achchuthan Shanmugasundram Tag Q3_24_NHS_review was removed from gene: ATXN7L3.
Tag Q3_24_MOI was removed from gene: ATXN7L3.
Likely inborn error of metabolism v7.9 DHRSX Achchuthan Shanmugasundram changed review comment from: Comment on list classification: This gene has already been recommended for promotion to green rating on the Congenital disorders of glycosylation panel (https://panelapp.genomicsengland.co.uk/panels/25/gene/DHRSX/). Hence, this gene should be promoted to green rating in the next GMS update.; to: Comment on list classification: This gene has already been recommended for promotion to green rating on the Congenital disorders of glycosylation panel (https://panelapp.genomicsengland.co.uk/panels/25/gene/DHRSX/). Hence, this gene should be promoted to green rating on this panel in the next GMS update.
Likely inborn error of metabolism v7.9 DHRSX Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available (three unrelated cases and functional evidence) for the promotion of this gene to green rating in the next GMS update.; to: Comment on list classification: This gene has already been recommended for promotion to green rating on the Congenital disorders of glycosylation panel (https://panelapp.genomicsengland.co.uk/panels/25/gene/DHRSX/). Hence, this gene should be promoted to green rating in the next GMS update.
Likely inborn error of metabolism v7.9 DHRSX Achchuthan Shanmugasundram Entity copied from Congenital disorders of glycosylation v6.8
Likely inborn error of metabolism v7.9 DHRSX Achchuthan Shanmugasundram gene: DHRSX was added
gene: DHRSX was added to Likely inborn error of metabolism. Sources: Expert Review Amber
Q3_24_promote_green, Pseudoautosomal region 1 tags were added to gene: DHRSX.
Mode of inheritance for gene: DHRSX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHRSX were set to 38821050
Phenotypes for gene: DHRSX were set to congenital disorder of glycosylation, MONDO:0015286
Penetrance for gene: DHRSX were set to Complete
Likely inborn error of metabolism v7.8 DDOST Achchuthan Shanmugasundram Classified gene: DDOST as Amber List (moderate evidence)
Likely inborn error of metabolism v7.8 DDOST Achchuthan Shanmugasundram Added comment: Comment on list classification: Two unrelated cases and functional evidence are available in support of the association of this gene with congenital disorder glycosylation and hence recommended for green rating on the Congenital disorders of glycosylation panel (https://panelapp.genomicsengland.co.uk/panels/25/gene/DDOST/). This gene should therefore promoted to green rating in the next GMS update.
Likely inborn error of metabolism v7.8 DDOST Achchuthan Shanmugasundram Gene: ddost has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v7.7 DDOST Achchuthan Shanmugasundram Phenotypes for gene: DDOST were changed from ?Congenital disorder of glycosylation, type Ir 614507 to Congenital disorder of glycosylation, type Ir, OMIM:614507
Likely inborn error of metabolism v7.7 DDOST Achchuthan Shanmugasundram Publications for gene: DDOST were set to 22305527
Likely inborn error of metabolism v7.6 DDOST Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: DDOST.
Likely inborn error of metabolism v7.6 DDOST Achchuthan Shanmugasundram reviewed gene: DDOST: Rating: GREEN; Mode of pathogenicity: None; Publications: 22305527, 34462534; Phenotypes: Congenital disorder of glycosylation, type Ir, OMIM:614507; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.36 AFF3_GCC Sarah Leigh Classified STR: AFF3_GCC as Red List (low evidence)
Intellectual disability v8.36 AFF3_GCC Sarah Leigh Added comment: Comment on list classification: This STR is rated as red, because it is not yet NGS validated.
Intellectual disability v8.36 AFF3_GCC Sarah Leigh Str: aff3_gcc has been classified as Red List (Low Evidence).
Intellectual disability v8.35 AFF3_GCC Sarah Leigh Tag STR tag was added to STR: AFF3_GCC.
Tag NGS Not Validated tag was added to STR: AFF3_GCC.
Hereditary neuropathy or pain disorder v6.138 LRP12_CGG Sarah Leigh Classified STR: LRP12_CGG as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.138 LRP12_CGG Sarah Leigh Added comment: Comment on list classification: This STR is rated as amber, because it is not yet NGS validated.
Hereditary neuropathy or pain disorder v6.138 LRP12_CGG Sarah Leigh Str: lrp12_cgg has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.137 LRP12_CGG Sarah Leigh Tag STR tag was added to STR: LRP12_CGG.
Tag NGS Not Validated tag was added to STR: LRP12_CGG.
Hereditary neuropathy v1.495 LRP12_CGG Sarah Leigh Classified STR: LRP12_CGG as Amber List (moderate evidence)
Hereditary neuropathy v1.495 LRP12_CGG Sarah Leigh Added comment: Comment on list classification: This STR is rated as amber, as it is not NGS validated.
Hereditary neuropathy v1.495 LRP12_CGG Sarah Leigh Str: lrp12_cgg has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy v1.494 LRP12_CGG Sarah Leigh Tag NGS Not Validated tag was added to STR: LRP12_CGG.
Hereditary neuropathy v1.494 LRP12_CGG Sarah Leigh GRCh37 position for LRP12_CGG was changed from - to 105601201-105601227.
GRCh38 position for LRP12_CGG was changed from 104588961-104588999 to 104588973-104588999.
Paediatric disorders - additional genes v6.3 IGFALS Tracy Lester gene: IGFALS was added
gene: IGFALS was added to Paediatric disorders - additional genes. Sources: NHS GMS
Mode of inheritance for gene: IGFALS was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IGFALS were set to short stature
Penetrance for gene: IGFALS were set to unknown
Review for gene: IGFALS was set to GREEN
gene: IGFALS was marked as current diagnostic
Added comment: This gene is on the R453 panel but absent from R27 - adding so that syndromic cases of short stature have all genes on the R453 panel covered.
Sources: NHS GMS
Paediatric disorders - additional genes v6.3 HMGA2 Tracy Lester gene: HMGA2 was added
gene: HMGA2 was added to Paediatric disorders - additional genes. Sources: NHS GMS
Mode of inheritance for gene: HMGA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Penetrance for gene: HMGA2 were set to unknown
Review for gene: HMGA2 was set to GREEN
gene: HMGA2 was marked as current diagnostic
Added comment: This gene is on the R453 panel but absent from R27 - adding so that syndromic cases of short stature have all genes on the R453 panel covered.
Sources: NHS GMS
Paediatric disorders - additional genes v6.3 PLAG1 Tracy Lester gene: PLAG1 was added
gene: PLAG1 was added to Paediatric disorders - additional genes. Sources: NHS GMS
Mode of inheritance for gene: PLAG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLAG1 were set to 28796236
Phenotypes for gene: PLAG1 were set to short stature
Penetrance for gene: PLAG1 were set to unknown
gene: PLAG1 was marked as current diagnostic
Added comment: This gene is on the R453 panel but absent from R27 - adding so that syndromic cases of short stature have all genes on the R453 panel covered.
Sources: NHS GMS
Intellectual disability v8.35 PABPC1 Cassandra Smith reviewed gene: PABPC1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.35 RNU4-2 Eleanor Williams Publications for gene: RNU4-2 were set to 38821540; 38645094
Intellectual disability v8.34 RNU4-2 Eleanor Williams edited their review of gene: RNU4-2: Added comment: Additional paper PMID:38991538 Chen et al 2024 supporting the association of RNU4-2 variants with a neurodevelopmental disorder. Data from the 100,000 Genomes Project dataset (used in other studies).; Changed publications to: 38991538
Optic neuropathy v4.38 DNAJC30 Eleanor Williams reviewed gene: DNAJC30: Rating: ; Mode of pathogenicity: None; Publications: 38107630; Phenotypes: ; Mode of inheritance: None
Haematological malignancies for rare disease v1.18 SH2B3 Dmitrijs Rots reviewed gene: SH2B3: Rating: GREEN; Mode of pathogenicity: None; Publications: 37206266; Phenotypes: myeloproliferation and multi‐organ autoimmunity; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy v1.493 LRP12 Dmitrijs Rots reviewed gene: LRP12: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Primary immunodeficiency or monogenic inflammatory bowel disease v7.21 EP300 Arina Puzriakova Phenotypes for gene: EP300 were changed from Rubinstein-Taybi Syndrome; Hypogammaglobulinemia; short stature; Intellectual disability; broad thumbs and first toes; highly arched eyebrows; long eyelashes; downslanting palpebral fissures; convex nasal ridge; low hanging columella; highly arched palate; micrognathia to Rubinstein-Taybi syndrome 2, OMIM:613684
Primary immunodeficiency or monogenic inflammatory bowel disease v7.20 EP300 Arina Puzriakova Classified gene: EP300 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v7.20 EP300 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update. Disruption of the immune system including recurrent and/or severe infections has been reported in a significant proportion (70%) of patients with Rubinstein-Taybi syndrome, supporting inclusion on this panel.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.20 EP300 Arina Puzriakova Gene: ep300 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v7.19 EP300 Arina Puzriakova Tag Q3_24_promote_green tag was added to gene: EP300.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.19 CREBBP Arina Puzriakova Classified gene: CREBBP as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v7.19 CREBBP Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update. Disruption of the immune system including recurrent and/or severe infections has been reported in a significant proportion (70%) of patients with Rubinstein-Taybi syndrome, supporting inclusion on this panel.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.19 CREBBP Arina Puzriakova Gene: crebbp has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v7.18 CREBBP Arina Puzriakova Tag Q3_24_promote_green tag was added to gene: CREBBP.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.18 CREBBP Arina Puzriakova Phenotypes for gene: CREBBP were changed from Rubinstein-Taybi Syndrome; Hypogammaglobulinemia; short stature; Intellectual disability; broad thumbs and first toes; highly arched eyebrows; long eyelashes; downslanting palpebral fissures; convex nasal ridge; low hanging columella; highly arched palate; micrognathia to Rubinstein-Taybi syndrome 1, OMIM:180849
Primary immunodeficiency or monogenic inflammatory bowel disease v7.17 GNAI2 Arina Puzriakova Classified gene: GNAI2 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v7.17 GNAI2 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update. Immunodeficiency/immunodysregulation was the most common feature reported in patients with pathogenic GNAI2 variants, supporting inclusion on this panel.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.17 GNAI2 Arina Puzriakova Gene: gnai2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.34 GNAI2 Arina Puzriakova Classified gene: GNAI2 as Amber List (moderate evidence)
Intellectual disability v8.34 GNAI2 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this to Green at the next GMS panel update. Multiple individuals reported with heterozygous variants supported by functional studies. In PMID:39298586 neurodevelopmental delay in early childhood was reported in 68% of cases, which progressed to ID as patients became older in 53%. Overall patients present with a highly variable phenotype that would be suited to the R27 Paediatic disorders super panel - inclusion on the ID panel would feed into R27.
Intellectual disability v8.34 GNAI2 Arina Puzriakova Gene: gnai2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.33 GNAI2 Arina Puzriakova Mode of pathogenicity for gene: GNAI2 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 Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v8.32 GNAI2 Arina Puzriakova Mode of pathogenicity for gene: GNAI2 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 Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v8.32 GNAI2 Arina Puzriakova Mode of pathogenicity for gene: GNAI2 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Intellectual disability v8.31 GNAI2 Arina Puzriakova Publications for gene: GNAI2 were set to 31036916; 27787898
Primary immunodeficiency or monogenic inflammatory bowel disease v7.16 GNAI2 Arina Puzriakova Publications for gene: GNAI2 were set to PMID: 39298586
Intellectual disability v8.30 GNAI2 Arina Puzriakova Tag Q3_24_promote_green tag was added to gene: GNAI2.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.15 GNAI2 Arina Puzriakova Tag Q3_24_promote_green tag was added to gene: GNAI2.
Intellectual disability v8.30 GNAI2 Arina Puzriakova edited their review of gene: GNAI2: Added comment: Ham et al. (2024) (PMID: 39298586) - 20 individuals from 18 unrelated families with heterozygous GOF missense variants in GNAI2 and highly heterogenous clinical presentations. Most commonly observed was disruption of the immune system, with almost 90% of cases exhibiting recurrent, unusual, and/or severe infections. Other features include birth defects, growth abnormalities, neurodevelopmental delay progressing to ID at later stages, brain structural abnormalities and various dysmorphic features. Authors dubbed the syndromic disorder with the acronym MAGIS - Midline malformations of the brain,
Anterior hypopituitarism, Growth retardation, Immunodeficiency/immunodysregulation, Skeletal
abnormalities.; Changed publications to: 31036916, 27787898, 39298586
Primary immunodeficiency or monogenic inflammatory bowel disease v7.15 GNAI2 Arina Puzriakova reviewed gene: GNAI2: Rating: ; Mode of pathogenicity: None; Publications: 39298586; Phenotypes: ; Mode of inheritance: None
Hereditary neuropathy or pain disorder v6.137 MAPK8IP3 Eleanor Williams Classified gene: MAPK8IP3 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.137 MAPK8IP3 Eleanor Williams Added comment: Comment on list classification: Promoting to amber and tagging for promotion to green, but GLH expert review is needed to decide whether there is clear enough mode of inheritance data and a strong enough association with neuropathy to report diagnostically particularly for people with isolated neuropathy presentations who are more likely to be tested via this route.
Hereditary neuropathy or pain disorder v6.137 MAPK8IP3 Eleanor Williams Gene: mapk8ip3 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.136 MAPK8IP3 Eleanor Williams Phenotypes for gene: MAPK8IP3 were changed from developmental delay; motor axonal neuropathy to Neurodevelopmental disorder with or without variable brain abnormalities, OMIM:618443; neurodevelopmental disorder with or without variable brain abnormalities, NEDBA, MONDO:0032755
Hereditary neuropathy or pain disorder v6.135 MAPK8IP3 Eleanor Williams Mode of inheritance for gene: MAPK8IP3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary neuropathy or pain disorder v6.134 MAPK8IP3 Eleanor Williams Tag Q3_24_promote_green tag was added to gene: MAPK8IP3.
Tag Q3_24_NHS_review tag was added to gene: MAPK8IP3.
Tag Q3_24_expert_review tag was added to gene: MAPK8IP3.
Limb disorders v6.3 COL5A1 Eleanor Williams commented on gene: COL5A1
Limb disorders v6.3 COL5A1 Eleanor Williams Tag curated_removed tag was added to gene: COL5A1.
Paediatric disorders - additional genes v6.3 COL5A1 Eleanor Williams Classified gene: COL5A1 as Amber List (moderate evidence)
Paediatric disorders - additional genes v6.3 COL5A1 Eleanor Williams Added comment: Comment on list classification: Promoting to amber with a provisional recommendation to green if it is decided this phenotype is appropriate for the panel.
Paediatric disorders - additional genes v6.3 COL5A1 Eleanor Williams Gene: col5a1 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v6.3 COL5A1 Eleanor Williams Classified gene: COL5A1 as Amber List (moderate evidence)
Paediatric disorders - additional genes v6.3 COL5A1 Eleanor Williams Added comment: Comment on list classification: Promoting to amber with a provisional recommendation to green if it is decided this phenotype is appropriate for the panel.
Paediatric disorders - additional genes v6.3 COL5A1 Eleanor Williams Gene: col5a1 has been classified as Amber List (Moderate Evidence).
Haematological malignancies cancer susceptibility v4.6 PTPN13 Arina Puzriakova Tag watchlist tag was added to gene: PTPN13.
Paediatric or syndromic cardiomyopathy v6.3 KBTBD13 Achchuthan Shanmugasundram Classified gene: KBTBD13 as Amber List (moderate evidence)
Paediatric or syndromic cardiomyopathy v6.3 KBTBD13 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although three unrelated families and evidence from mouse model are available in support of the association, all cases were reported with the same founder variant. Hence, this gene should be rated amber with the current evidence.
Paediatric or syndromic cardiomyopathy v6.3 KBTBD13 Achchuthan Shanmugasundram Gene: kbtbd13 has been classified as Amber List (Moderate Evidence).
Haematological malignancies cancer susceptibility v4.6 PTPN13 Arina Puzriakova Classified gene: PTPN13 as Amber List (moderate evidence)
Haematological malignancies cancer susceptibility v4.6 PTPN13 Arina Puzriakova Added comment: Comment on list classification: Rating Amber as only 2 unrelated cases reported to date with germline variants in PTPN13, presenting with ALL (PMID: 35643866). Not associated with any phenotype in OMIM but has been classified 'moderate' for 'PTPN13 related predisposition to bone marrow failure' in G2P. Adding watchlist tag to monitor for additional cases that corroborate this gene-disease association before promoting to green.
Haematological malignancies cancer susceptibility v4.6 PTPN13 Arina Puzriakova Gene: ptpn13 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v6.2 COL5A1 Eleanor Williams changed review comment from: Adding this gene for consideration for this panel following review of the gene on the Limb disorders panel. This 'Paediatric disorders - additional genes' panel appears a better fit than Limb disorders if the condition is to be included in the Paediatric disorders R27 test analyses.

However, consideration of whether the EDS phenotype is the within the scope of the Paediatric disorders panel needs to be reviewed before promoting this gene to green.
Sources: Expert Review; to: Adding this gene for consideration for this panel following review of the gene by Tracy Lester (Genetics laboratory, Oxford UK) on the Limb disorders panel. The 'Paediatric disorders - additional genes' panel appears a better fit than Limb disorders if the condition is to be included in the Paediatric disorders R27 superpanel test analyses.

However, consideration of whether the EDS phenotype is the within the scope of the Paediatric disorders panel needs to be reviewed before promoting this gene to green.
Sources: Expert Review
Paediatric or syndromic cardiomyopathy v6.2 KBTBD13 Achchuthan Shanmugasundram Phenotypes for gene: KBTBD13 were changed from to Nemaline myopathy 6, autosomal dominant, OMIM:609273; intrinsic cardiomyopathy, MONDO:0000591
Paediatric disorders - additional genes v6.2 COL5A1 Eleanor Williams Tag Q3_24_promote_green tag was added to gene: COL5A1.
Tag Q3_24_NHS_review tag was added to gene: COL5A1.
Tag Q3_24_expert_review tag was added to gene: COL5A1.
Paediatric or syndromic cardiomyopathy v6.1 KBTBD13 Achchuthan Shanmugasundram reviewed gene: KBTBD13: Rating: AMBER; Mode of pathogenicity: None; Publications: 36335629; Phenotypes: Nemaline myopathy 6, autosomal dominant, OMIM:609273, intrinsic cardiomyopathy, MONDO:0000591; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Paediatric disorders - additional genes v6.2 COL5A1 Eleanor Williams gene: COL5A1 was added
gene: COL5A1 was added to Paediatric disorders - additional genes. Sources: Expert Review
Mode of inheritance for gene: COL5A1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: COL5A1 were set to 21611149; 20847697
Phenotypes for gene: COL5A1 were set to Ehlers-Danlos syndrome, classic type, 1, OMIM:130000; Ehlers-Danlos syndrome, classic type, 1, MONDO:0019567
Review for gene: COL5A1 was set to AMBER
Added comment: Adding this gene for consideration for this panel following review of the gene on the Limb disorders panel. This 'Paediatric disorders - additional genes' panel appears a better fit than Limb disorders if the condition is to be included in the Paediatric disorders R27 test analyses.

However, consideration of whether the EDS phenotype is the within the scope of the Paediatric disorders panel needs to be reviewed before promoting this gene to green.
Sources: Expert Review
Hereditary neuropathy or pain disorder v6.134 MT-ND6 Achchuthan Shanmugasundram Classified gene: MT-ND6 as Red List (low evidence)
Hereditary neuropathy or pain disorder v6.134 MT-ND6 Achchuthan Shanmugasundram Gene: mt-nd6 has been classified as Red List (Low Evidence).
Hereditary neuropathy or pain disorder v6.133 MT-ND6 Achchuthan Shanmugasundram Publications for gene: MT-ND6 were set to PMID: 20301353
Hereditary neuropathy or pain disorder v6.132 MT-ND6 Achchuthan Shanmugasundram Phenotypes for gene: MT-ND6 were changed from LHON; peripheral neuropathy to Leber hereditary optic neuropathy
Hereditary neuropathy or pain disorder v6.131 MT-ND6 Achchuthan Shanmugasundram reviewed gene: MT-ND6: Rating: RED; Mode of pathogenicity: None; Publications: 17724295, 20301353, 27111573, 38975939; Phenotypes: ; Mode of inheritance: MITOCHONDRIAL
Cystic kidney disease v7.7 CYS1 Arina Puzriakova Entity copied from Renal ciliopathies v3.15
Cystic kidney disease v7.7 CYS1 Arina Puzriakova gene: CYS1 was added
gene: CYS1 was added to Cystic kidney disease. Sources: Expert Review Amber,Literature
watchlist tags were added to gene: CYS1.
Mode of inheritance for gene: CYS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CYS1 were set to 34521872
Phenotypes for gene: CYS1 were set to Polycystic kidney disease, MONDO:0020642
Renal ciliopathies v3.15 CYS1 Arina Puzriakova Classified gene: CYS1 as Amber List (moderate evidence)
Renal ciliopathies v3.15 CYS1 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). Not yet associated with any phenotype in OMIM or G2P. One family with biallelic pathogenic variants and having severe childhood polycystic kidney disease and congenital hepatic fibrosis (PMID: 34521872). Cystin (product of CYS1) is expressed in primary apical cilia of renal ductal epithelial cells and the knockout mouse model phenocopies human polycystic kidney disease, providing strong support for this association (PMID: 11854326)

Overall sufficient evidence for amber rating, but additional cases required before promotion to green (added watchlist tag).
Renal ciliopathies v3.15 CYS1 Arina Puzriakova Gene: cys1 has been classified as Amber List (Moderate Evidence).
Renal ciliopathies v3.14 CYS1 Arina Puzriakova Tag watchlist tag was added to gene: CYS1.
Hereditary neuropathy or pain disorder v6.131 PIGG Christopher Record gene: PIGG was added
gene: PIGG was added to Hereditary neuropathy or pain disorder. Sources: Literature
Mode of inheritance for gene: PIGG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGG were set to 39444079
Phenotypes for gene: PIGG were set to HMN
Review for gene: PIGG was set to GREEN
Added comment: Recessive variants in PIGG cause a inherited motor neuropathy with conduction block and/or temporal dispersion (39444079). This can be a pure neuropathy of part of a wider IGD syndrome to include cerebellar features, developmental delay, intellectual disability.
Sources: Literature
Hereditary neuropathy or pain disorder v6.131 LRP12_CGG Christopher Record STR: LRP12_CGG was added
STR: LRP12_CGG was added to Hereditary neuropathy or pain disorder. Sources: Literature
Mode of inheritance for STR: LRP12_CGG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for STR: LRP12_CGG were set to 39013564
Phenotypes for STR: LRP12_CGG were set to CMT2, HMN
Review for STR: LRP12_CGG was set to GREEN
Added comment: CGG repeat expansion as cause for autosomal dominant inherited neuropathy in 44 Japanese patients
STR only
Sources: Literature
Hereditary neuropathy or pain disorder v6.131 NOTCH2NL Christopher Record gene: NOTCH2NL was added
gene: NOTCH2NL was added to Hereditary neuropathy or pain disorder. Sources: Literature
Mode of inheritance for gene: NOTCH2NL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOTCH2NL were set to 36948577; 37749855; 34675106
Mode of pathogenicity for gene: NOTCH2NL was set to Other
Review for gene: NOTCH2NL was set to GREEN
Added comment: [NB NOTCH2NL selected from gene drop down as NOTCH2NLC not available]
NOTCH2NLC GGC repeat expansion
Reported pure CMT in 26 cases from Japan (36948577), and 7cases from Taiwan (34675106). Chinese NOTC2NLC related NIID cohort also showed peripheral neuropathy in significant proportion (37749855). Anecdotally found in family with CMT of European ancestry (unpublished).
Phenotypes included CMT2, CMTi and HMN
Sources: Literature
Intellectual disability v8.30 WDR83OS Achchuthan Shanmugasundram Classified gene: WDR83OS as Amber List (moderate evidence)
Intellectual disability v8.30 WDR83OS Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there are nine unrelated families reported with biallelic WDR83OS variants and a neurodevelopmental disorder comprising intellectual disability/ developmental delay. Hence, this gene can be promoted to green rating in the next GMS update.
Intellectual disability v8.30 WDR83OS Achchuthan Shanmugasundram Gene: wdr83os has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.29 WDR83OS Achchuthan Shanmugasundram Phenotypes for gene: WDR83OS were changed from Intellectual disability to complex neurodevelopmental disorder, MONDO:0100038; intellectual disability, MONDO:0001071
Intellectual disability v8.29 WDR83OS Achchuthan Shanmugasundram Publications for gene: WDR83OS were set to 30250217
Intellectual disability v8.28 WDR83OS Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: WDR83OS.
Intellectual disability v8.28 WDR83OS Achchuthan Shanmugasundram reviewed gene: WDR83OS: Rating: GREEN; Mode of pathogenicity: None; Publications: 30250217, 39471804; Phenotypes: complex neurodevelopmental disorder, MONDO:0100038, intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v7.6 ACSF3 Arina Puzriakova Publications for gene: ACSF3 were set to 21785126; 26915364; 30740739; 26827111; 27604308; 21841779
Likely inborn error of metabolism v7.5 ACSF3 Arina Puzriakova Phenotypes for gene: ACSF3 were changed from Combined methylmalonic and malonic aciduria (Organic acidurias); Combined malonic and methylmalonic aciduria to Combined malonic and methylmalonic aciduria, OMIM:614265
Likely inborn error of metabolism v7.5 ACSF3 Arina Puzriakova Publications for gene: ACSF3 were set to 27604308
Likely inborn error of metabolism v7.4 ACSF3 Arina Puzriakova commented on gene: ACSF3
Intellectual disability v8.28 MARK2 Achchuthan Shanmugasundram Classified gene: MARK2 as Amber List (moderate evidence)
Intellectual disability v8.28 MARK2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, 31 individuals were reported with intellectual disability/ developmental delay and with monoallelic MARK2 variants. ID/ DD was severe in seven, moderate in two, mild and/or borderline in four and unspecified in 17. In addition, functional evidence is also available.

This gene can therefore be promoted to green rating in the next GMS update.
Intellectual disability v8.28 MARK2 Achchuthan Shanmugasundram Gene: mark2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.27 MARK2 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Intellectual disability v8.27 MARK2 Achchuthan Shanmugasundram Phenotypes for gene: MARK2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v8.26 MARK2 Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: MARK2.
Intellectual disability v8.26 MARK2 Achchuthan Shanmugasundram Phenotypes for gene: MARK2 were changed from Neurodevelopmental disorder MONDO:0700092 to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v8.25 MARK2 Achchuthan Shanmugasundram reviewed gene: MARK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 39419027, 39436150; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v6.131 LRP12 Christopher Record reviewed gene: LRP12: Rating: GREEN; Mode of pathogenicity: Other; Publications: 39013564; Phenotypes: CMT2, HMN; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v7.13 AASS Arina Puzriakova Classified gene: AASS as Amber List (moderate evidence)
Early onset or syndromic epilepsy v7.13 AASS Arina Puzriakova Gene: aass has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v7.12 AASS Arina Puzriakova gene: AASS was added
gene: AASS was added to Early onset or syndromic epilepsy. Sources: Literature
Q3_24_promote_green tags were added to gene: AASS.
Mode of inheritance for gene: AASS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AASS were set to 23890588; 10775527; 27604308; 23570448
Phenotypes for gene: AASS were set to Hyperlysinemia, OMIM:238700; Hyperlysinemia (disease), MONDO:0009388
Review for gene: AASS was set to GREEN
Added comment: AASS associated with hyperlysinemia in ClinGen (definitive), G2P (strong) and OMIM. At least 10 probands in 4 publications (PMIDs: 23890588, 10775527, 27604308, 23570448), of which at least 4 cases had epilepsy. Seizures can represent an early feature of the disorder which supports inclusion of AASS on this panel.

This gene-disease relationship is supported by its biochemical function in lysine catabolism and a knock-in mouse model which recapitulates the human phenotype of hyperlysinemia (PMID: 35135854).
Sources: Literature
Likely inborn error of metabolism v7.4 AASS Arina Puzriakova Publications for gene: AASS were set to 27604308
Likely inborn error of metabolism v7.3 AASS Arina Puzriakova commented on gene: AASS
Severe microcephaly v7.6 SLC4A10 Arina Puzriakova Entity copied from Intellectual disability v8.25
Severe microcephaly v7.6 SLC4A10 Arina Puzriakova gene: SLC4A10 was added
gene: SLC4A10 was added to Severe microcephaly. Sources: Expert Review Amber,Other
Q3_24_promote_green tags were added to gene: SLC4A10.
Mode of inheritance for gene: SLC4A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC4A10 were set to 37459438; 38054405; 31130284
Phenotypes for gene: SLC4A10 were set to Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, OMIM:620746
Early onset or syndromic epilepsy v7.11 SLC4A10 Arina Puzriakova Entity copied from Intellectual disability v8.25
Early onset or syndromic epilepsy v7.11 SLC4A10 Arina Puzriakova gene: SLC4A10 was added
gene: SLC4A10 was added to Early onset or syndromic epilepsy. Sources: Expert Review Amber,Other
Q3_24_promote_green tags were added to gene: SLC4A10.
Mode of inheritance for gene: SLC4A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC4A10 were set to 37459438; 38054405; 31130284
Phenotypes for gene: SLC4A10 were set to Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, OMIM:620746
Intellectual disability v8.25 SLC4A10 Arina Puzriakova Tag Q3_24_promote_green tag was added to gene: SLC4A10.
Intellectual disability v8.25 SLC4A10 Arina Puzriakova Publications for gene: SLC4A10 were set to 37459438; 38054405
Intellectual disability v8.24 SLC4A10 Arina Puzriakova Classified gene: SLC4A10 as Amber List (moderate evidence)
Intellectual disability v8.24 SLC4A10 Arina Puzriakova Added comment: Comment on list classification: This gene is associated with a relevant phenotype in OMIM (MIM# 620746). Over 10 unrelated cases reported in literature with biallelic variants in this gene, presenting with a neurodevelopmental disorder characterised by hypotonia, delayed psychomotor development and intellectual impairment. Microcephaly (<−3 SDS) and epilepsy are also variably observed but there are sufficient to rate as green in the context of these features.

Overall sufficient evidence to promote this gene to Green at the next GMS panel update.
Intellectual disability v8.24 SLC4A10 Arina Puzriakova Gene: slc4a10 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.23 SLC4A10 Arina Puzriakova Phenotypes for gene: SLC4A10 were changed from to Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities, OMIM:620746
White matter disorders and cerebral calcification - narrow panel v6.2 SLC13A3 Arina Puzriakova Entity copied from Mitochondrial disorders v8.7
White matter disorders and cerebral calcification - narrow panel v6.2 SLC13A3 Arina Puzriakova gene: SLC13A3 was added
gene: SLC13A3 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert Review Amber,Literature
Q3_24_promote_green tags were added to gene: SLC13A3.
Mode of inheritance for gene: SLC13A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC13A3 were set to 30635937; 34966709; 35527102; 37290914; 38235040; 33340416
Phenotypes for gene: SLC13A3 were set to Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate, OMIM:618384
Penetrance for gene: SLC13A3 were set to Complete
Likely inborn error of metabolism v7.3 SLC13A3 Arina Puzriakova Entity copied from Mitochondrial disorders v8.7
Likely inborn error of metabolism v7.3 SLC13A3 Arina Puzriakova gene: SLC13A3 was added
gene: SLC13A3 was added to Likely inborn error of metabolism. Sources: Expert Review Amber,Literature
Q3_24_promote_green tags were added to gene: SLC13A3.
Mode of inheritance for gene: SLC13A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC13A3 were set to 30635937; 34966709; 35527102; 37290914; 38235040; 33340416
Phenotypes for gene: SLC13A3 were set to Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate, OMIM:618384
Penetrance for gene: SLC13A3 were set to Complete
Early onset or syndromic epilepsy v7.10 SLC13A3 Arina Puzriakova Tag Q3_24_promote_green tag was added to gene: SLC13A3.
Mitochondrial disorders v8.7 SLC13A3 Arina Puzriakova Tag Q3_24_promote_green tag was added to gene: SLC13A3.
Early onset or syndromic epilepsy v7.10 SLC13A3 Arina Puzriakova Publications for gene: SLC13A3 were set to 38235040; 34966709; 30635937
Mitochondrial disorders v8.7 SLC13A3 Arina Puzriakova Publications for gene: SLC13A3 were set to PMID: 33340416; PMID: 30635937
Mitochondrial disorders v8.6 SLC13A3 Arina Puzriakova Classified gene: SLC13A3 as Amber List (moderate evidence)
Mitochondrial disorders v8.6 SLC13A3 Arina Puzriakova Added comment: Comment on list classification: This gene is associated with a relevant phenotype in OMIM (MIM# 618384). At least 9 unrelated cases with biallelic variants in this gene and acute reversible leukoencephalopathy with increased urinary α-ketoglutarate, arising in the context of a febrile illness (PMID: 30635937; 34966709; 35527102; 37290914; 38235040).

Sufficient evidence to promote SLC13A3 to Green at the next GMS panel update.
Mitochondrial disorders v8.6 SLC13A3 Arina Puzriakova Gene: slc13a3 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v7.9 SLC13A3 Arina Puzriakova Classified gene: SLC13A3 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v7.9 SLC13A3 Arina Puzriakova Added comment: Comment on list classification: This gene is associated with a relevant phenotype in OMIM (MIM# 618384). At least 9 unrelated cases with biallelic variants in this gene and acute reversible leukoencephalopathy with increased urinary α-ketoglutarate, arising in the context of a febrile illness (PMID: 30635937; 34966709; 35527102; 37290914; 38235040).

Sufficient evidence to promote SLC13A3 to Green at the next GMS panel update.
Early onset or syndromic epilepsy v7.9 SLC13A3 Arina Puzriakova Gene: slc13a3 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v8.5 SLC13A3 Arina Puzriakova Phenotypes for gene: SLC13A3 were changed from Sodium dicarboxylate cotransporter 3 deficiency; Increased urinary dicarboxylic acids, alpha-ketoglutarate, fumarate, N-acetylaspartate; Encephalopathy; Ataxia to Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate, OMIM:618384
Early onset or syndromic epilepsy v7.8 SLC13A3 Arina Puzriakova Phenotypes for gene: SLC13A3 were changed from to Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate, OMIM:618384
Respiratory ciliopathies including non-CF bronchiectasis v3.21 TAPT1 Arina Puzriakova Mode of inheritance for gene: TAPT1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Respiratory ciliopathies including non-CF bronchiectasis v3.20 TAPT1 Arina Puzriakova Classified gene: TAPT1 as Red List (low evidence)
Respiratory ciliopathies including non-CF bronchiectasis v3.20 TAPT1 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red in line with the Red review by Steven Cowman (Bristol Royal Infirmary). No reports of relevant phenotype associated with this gene.
Respiratory ciliopathies including non-CF bronchiectasis v3.20 TAPT1 Arina Puzriakova Gene: tapt1 has been classified as Red List (Low Evidence).
Hereditary ataxia v1.337 NUS1 Achchuthan Shanmugasundram Classified gene: NUS1 as Green List (high evidence)
Hereditary ataxia v1.337 NUS1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots, there is sufficient evidence available (~10 unrelated patients and functional evidence) for the promotion of this gene to green rating.
Hereditary ataxia v1.337 NUS1 Achchuthan Shanmugasundram Gene: nus1 has been classified as Green List (High Evidence).
Hereditary ataxia v1.336 NUS1 Achchuthan Shanmugasundram Phenotypes for gene: NUS1 were changed from intellectual disability; seizures; ataxia; dystonia; tremor to hereditary ataxia, MONDO:0100309
Hereditary ataxia v1.335 NUS1 Achchuthan Shanmugasundram Publications for gene: NUS1 were set to 33731878; 32334381; 32485575; 31656175
Hereditary ataxia v1.334 NUS1 Achchuthan Shanmugasundram reviewed gene: NUS1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31656175, 32485575, 32959737, 33731878, 38291835; Phenotypes: hereditary ataxia, MONDO:0100309; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v7.6 NUS1 Achchuthan Shanmugasundram Classified gene: NUS1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v7.6 NUS1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (~10 unrelated patients and functional evidence) for the association of this gene with ataxia. Hence, this gene can be promoted to green rating in the next GMS update.
Ataxia and cerebellar anomalies - narrow panel v7.6 NUS1 Achchuthan Shanmugasundram Gene: nus1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v7.5 NUS1 Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: NUS1.
Ataxia and cerebellar anomalies - narrow panel v7.5 NUS1 Achchuthan Shanmugasundram gene: NUS1 was added
gene: NUS1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: NUS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NUS1 were set to 31656175; 32485575; 32959737; 33731878; 38291835
Phenotypes for gene: NUS1 were set to hereditary ataxia, MONDO:0100309
Review for gene: NUS1 was set to GREEN
Added comment: PMID:31656175 reported two unrelated patients with a novel de novo NUS1 variant and they presented with epileptic seizures with involuntary movement, ataxia, intellectual disability and scoliosis.

PMID:32485575 reported the identification of a novel heterozygous frameshift variant in NUS1 gene in five patients from a family with epilepsy. They all had cerebellar ataxia and tremor.

PMID:32959737 reported a 34-year-old female with NUS1 variant with a prominent and progressive generalised dystonia. She developed a slight head tremor at 18 months of age. Intellectual disability was diagnosed by second grade. She developed a mild but progressive gait ataxia, dysarthria, and dyscoordination of the hands.

PMID:33731878 reported three patients with de novo heterozygous NUS1 variants, of which two patients presented with ataxia. The third patient had no ataxia but was noted to have dysarthria. There is also functional evidence available from patient fibroblasts and zebrafish models.

PMID:38291835 reported five unrelated patients with NUS1 variants. They had onset of movement disorders ranging from birth to 13 years of age and four of them had mild gait ataxia.
Sources: Literature
Childhood onset dystonia, chorea or related movement disorder v6.3 NUS1 Achchuthan Shanmugasundram Classified gene: NUS1 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v6.3 NUS1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (seven unrelated cases) for the association of this gene with childhood-onset movement disorder including dystonia. Hence, this gene can be promoted to green rating in the next GMS update.
Childhood onset dystonia, chorea or related movement disorder v6.3 NUS1 Achchuthan Shanmugasundram Gene: nus1 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v6.2 NUS1 Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: NUS1.
Childhood onset dystonia, chorea or related movement disorder v6.2 NUS1 Achchuthan Shanmugasundram gene: NUS1 was added
gene: NUS1 was added to Childhood onset dystonia, chorea or related movement disorder. Sources: Literature
Mode of inheritance for gene: NUS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NUS1 were set to 32334381; 32959737; 38291835
Phenotypes for gene: NUS1 were set to movement disorder, MONDO:0005395
Review for gene: NUS1 was set to GREEN
Added comment: PMID:32334381 reported a patient with childhood onset static and focal upper limb dystonia and was diagnosed with a monoallelic NUS1 variant via WES.

PMID:32959737 reported a 34-year-old patient with autosomal dominant NUS1 variant and with a prominent and progressive generalised dystonia.

PMID:38291835 reported five unrelated patients ranging from 13 to 53 years of age with monoallelic NUS1 variant. They presented with movement disorder and its onset ranged from birth to 13 years of age. Three of them had dystonia.
Sources: Literature
Retinal disorders v7.1 PAX6 Achchuthan Shanmugasundram reviewed gene: PAX6: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Foveal hypoplasia 1, OMIM:136520, Microphthalmia/coloboma 12, OMIM:120200, ?Coloboma of optic nerve, OMIM:120430, Anterior segment dysgenesis 5, multiple subtypes, OMIM:604229; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v8.22 AFF3_GCC Sarah Leigh Tag NGS Not Validated was removed from STR: AFF3_GCC.
Intellectual disability v8.22 AFF3_GCC Sarah Leigh Tag NGS Not Validated tag was added to STR: AFF3_GCC.
Hereditary neuropathy v1.493 LRP12_CGG Arina Puzriakova LRP12 was changed to LRP12_CGG
Source Literature was removed from STR: LRP12_CGG.
Intellectual disability v8.22 AFF3_GCC Arina Puzriakova Gene was set to AFF3.
Intellectual disability v8.21 AFF3_GCC Arina Puzriakova AFF3 was changed to AFF3_GCC
Source Literature was removed from STR: AFF3_GCC.
Source Expert Review was added to STR: AFF3_GCC.
Publications for STR: AFF3_GCC were updated from PMID: 39313615 to 39313615
Intellectual disability v8.20 LINC01578 Sarah Leigh Tag new-gene-name tag was added to gene: LINC01578.
Tag Q3_24_promote_green tag was added to gene: LINC01578.
Tag Q3_24_NHS_review tag was added to gene: LINC01578.
Intellectual disability v8.20 LINC01578 Sarah Leigh reviewed gene: LINC01578: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v8.20 LINC01578 Sarah Leigh Classified gene: LINC01578 as Amber List (moderate evidence)
Intellectual disability v8.20 LINC01578 Sarah Leigh Gene: linc01578 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.19 AFF3 Riyaad Aungraheeta reviewed STR: AFF3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 39313615; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v8.19 AFF3 Riyaad Aungraheeta Deleted their review
Intellectual disability v8.19 AFF3 Riyaad Aungraheeta STR: AFF3 was added
STR: AFF3 was added to Intellectual disability. Sources: Literature
Mode of inheritance for STR: AFF3 was set to Unknown
Publications for STR: AFF3 were set to PMID: 39313615
Penetrance for STR: AFF3 were set to Incomplete
Review for STR: AFF3 was set to GREEN
Added comment: Sources: Literature
Early onset or syndromic epilepsy v7.7 AJAP1 Achchuthan Shanmugasundram Classified gene: AJAP1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v7.7 AJAP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although there are five unrelated cases, the epilepsy phenotype is broad and there is contradictory functional evidence. Hence, this gene is currently rated as amber.

The 'watchlist' tag has been added to keep track of any new evidence.
Early onset or syndromic epilepsy v7.7 AJAP1 Achchuthan Shanmugasundram Gene: ajap1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v7.6 AJAP1 Achchuthan Shanmugasundram Tag watchlist tag was added to gene: AJAP1.
Early onset or syndromic epilepsy v7.6 AJAP1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Hannah Knight, PMID:38985877 reported five unrelated individuals with monoallelic variants or a deletion in AJAP1 gene, of which four patients presented with epilepsy.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.; to: As reviewed by Hannah Knight, PMID:38985877 reported five unrelated individuals with monoallelic variants or a deletion in AJAP1 gene. Although four of these patients presented with seizures, the type of seizures varied across these individuals.

Two of these five cases had a conclusion of either 'benign' or 'unknown' in their evaluation of pathogenicity, where 'benign' was one of the four cases with seizures, where 'unknown' was the fifth case without seizures. One of the cases (Individual 1) has a missense variant that was evaluated as 'pathogenic'. But, functional studies in monoallelic knock in mice was not clearly supportive of this conclusion and the EEG in this mice appeared equivalent to wild type mouse. In addition, all missense variants of this gene in ClinVar are rated as VUS / benign.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Retinal disorders v7.1 FRMD7 Sarah Leigh changed review comment from: FRMD7 variants have been associated with Nystagmus 1, congenital, X-linked (OMIM:310700) and it is a definitive G2P gene for the same condition. In a multicenter study of the Genotypic and Phenotypic Spectrum of Foveal Hypoplasia (FH), Kuht et al (PMID: 35157951) report that FRMD7 variants are associated with 3.5% of the FH cases in the study population. This study also revealed that FRMD7 variants are involved in grade 1 FH or normal foveal morphology and consequently with a good visual acuity in the patients. It was postulated that this maybe due to the delayed action of the FRMD7 variants during development.; to: FRMD7 variants have been associated with Nystagmus 1, congenital, X-linked (OMIM:310700) and it is a definitive G2P gene for the same condition. In a multicenter study of the Genotypic and Phenotypic Spectrum of Foveal Hypoplasia (FH), Kuht et al (PMID: 35157951) report that FRMD7 variants are associated with 3.5% of the FH cases in the study population (a total of 17 FRMD7 variants are recorded in this study - supplementary file 4). This study also revealed that FRMD7 variants are involved in grade 1 FH or normal foveal morphology and consequently with a good visual acuity in the patients. It was postulated that this maybe due to the delayed action of the FRMD7 variants during development.
Retinal disorders v7.1 FRMD7 Sarah Leigh edited their review of gene: FRMD7: Changed rating: AMBER
Retinal disorders v7.1 FRMD7 Sarah Leigh reviewed gene: FRMD7: Rating: GREEN; Mode of pathogenicity: None; Publications: 35157951; Phenotypes: ; Mode of inheritance: None
Early onset or syndromic epilepsy v7.6 AJAP1 Achchuthan Shanmugasundram edited their review of gene: AJAP1: Changed rating: AMBER
Early onset or syndromic epilepsy v7.6 AJAP1 Achchuthan Shanmugasundram Tag Q3_24_promote_green was removed from gene: AJAP1.
Tag Q3_24_NHS_review was removed from gene: AJAP1.
Early onset or syndromic epilepsy v7.6 AJAP1 Achchuthan Shanmugasundram Deleted their comment
Cystic kidney disease v7.6 CYP24A1 Sarah Leigh changed review comment from: CYP24A1 variants have been associated with Hypercalcemia, infantile, 1 (OMIM:143880). PMIDs: 34307984; 22337913; 27105398; 28324001 report numerous biallelic CYP24A1 variants in cases of OMIM:143880, with the occurrence of kidney cysts. PMID: 34307984 also reports a family, where three of the members are monoallelic for CYP24A1 variants, but present with OMIM:143880 and 2/3 of these cases also have kidney cysts.; to: CYP24A1 variants have been associated with Hypercalcemia, infantile, 1 (OMIM:143880). PMIDs: 34307984; 22337913; 27105398; 28324001 report numerous biallelic CYP24A1 variants in cases of OMIM:143880, with the occurrence of kidney cysts. PMID: 34307984 also reports a family, where three of the members are monoallelic for CYP24A1 variants, but present with OMIM:143880 and 2/3 of these cases also have kidney cysts. However, as this is the only report of monoallelic variants for this gene associated with OMIM:143880, the mode of inheritance for this gene should be BIALLELIC, autosomal or pseudoautosomal.
Severe microcephaly v7.5 MIR17HG Arina Puzriakova Entity copied from Intellectual disability v8.19
Severe microcephaly v7.5 MIR17HG Arina Puzriakova gene: MIR17HG was added
gene: MIR17HG was added to Severe microcephaly. Sources: Expert Review,Expert Review Amber
deletions, watchlist, locus-type-rna-long-non-coding tags were added to gene: MIR17HG.
Mode of inheritance for gene: MIR17HG was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MIR17HG were set to 21892160; 19344873; 25391829; 26360630
Phenotypes for gene: MIR17HG were set to Feingold syndrome 2, 614326; FS2; Brachydactyly with short stature and microcephaly; Intellectual disability
Penetrance for gene: MIR17HG were set to Complete
Intellectual disability v8.19 MIR17HG Arina Puzriakova Classified gene: MIR17HG as Amber List (moderate evidence)
Intellectual disability v8.19 MIR17HG Arina Puzriakova Gene: mir17hg has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.19 MIR17HG Arina Puzriakova Classified gene: MIR17HG as Amber List (moderate evidence)
Intellectual disability v8.19 MIR17HG Arina Puzriakova Gene: mir17hg has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.18 MIR17HG Arina Puzriakova Source Expert Review was added to MIR17HG.
Rating Changed from No List (delete) to Red List (low evidence)
Intellectual disability v8.17 MIR17HG Arina Puzriakova All sources for gene: MIR17HG were removed
Intellectual disability v8.17 MIR17HG Arina Puzriakova All sources for gene: MIR17HG were removed
Optic neuropathy v4.38 MIEF1 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: MIEF1.
Tag Q3_24_NHS_review tag was added to gene: MIEF1.
Optic neuropathy v4.38 MIEF1 Sarah Leigh reviewed gene: MIEF1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Optic neuropathy v4.38 MIEF1 Sarah Leigh Classified gene: MIEF1 as Amber List (moderate evidence)
Optic neuropathy v4.38 MIEF1 Sarah Leigh Gene: mief1 has been classified as Amber List (Moderate Evidence).
Optic neuropathy v4.37 MIEF1 Sarah Leigh Phenotypes for gene: MIEF1 were changed from Optic atrophy 14 to Optic atrophy 14, OMIM:620550; optic atrophy 14, MONDO:0957824
Optic neuropathy v4.36 MIEF1 Sarah Leigh Publications for gene: MIEF1 were set to PMID: 33632269
Monogenic hearing loss v4.60 PLCG1 Sarah Leigh commented on gene: PLCG1: If PMID: 38260438 is accepted for publication, a green recommendation for PLCG1 would be made.
Monogenic hearing loss v4.60 PLCG1 Sarah Leigh changed review comment from: If PMID: 38260438 is accepted for publication, a green recommendation for PLCG1 would be made.; to: If the preprint PMID: 38260438 is accepted for publication, a green recommendation would be made for PLCG1.
Monogenic hearing loss v4.60 PLCG1 Sarah Leigh reviewed gene: PLCG1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Monogenic hearing loss v4.60 PLCG1 Sarah Leigh Publications for gene: PLCG1 were set to PMID: 38260438
Monogenic hearing loss v4.59 PLCG1 Sarah Leigh Classified gene: PLCG1 as Amber List (moderate evidence)
Monogenic hearing loss v4.59 PLCG1 Sarah Leigh Gene: plcg1 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v7.6 CYP24A1 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: CYP24A1.
Tag Q3_24_NHS_review tag was added to gene: CYP24A1.
Cystic kidney disease v7.6 CYP24A1 Sarah Leigh reviewed gene: CYP24A1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cystic kidney disease v7.6 CYP24A1 Sarah Leigh Phenotypes for gene: CYP24A1 were changed from cystic kidney disease; nephrocalcinosis; hypercalcaemia to Hypercalcemia, infantile, 1, OMIM:143880; hypercalcemia, infantile, 1, MONDO:0020739
Cystic kidney disease v7.5 CYP24A1 Sarah Leigh Classified gene: CYP24A1 as Amber List (moderate evidence)
Cystic kidney disease v7.5 CYP24A1 Sarah Leigh Gene: cyp24a1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.16 LINC01578 Zornitza Stark gene: LINC01578 was added
gene: LINC01578 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: LINC01578 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LINC01578 were set to 39442041
Phenotypes for gene: LINC01578 were set to Neurodevelopmental disorder, MONDO:0700092, CHASERR-related
Review for gene: LINC01578 was set to GREEN
Added comment: CHASERR (aka LINC01578) encodes a human long noncoding RNA (lncRNA) adjacent to CHD2, a coding gene in which de novo loss-of-function variants cause developmental and epileptic encephalopathy. Three unrelated children reported with a syndromic, early-onset neurodevelopmental disorder, each of whom had a de novo deletion in the CHASERR locus. The children had severe encephalopathy, shared facial dysmorphisms, cortical atrophy, and cerebral hypomyelination - a phenotype that is distinct from the phenotypes of patients with CHD2 haploinsufficiency. CHASERR deletion results in increased CHD2 protein abundance in patient-derived cell lines and increased expression of the CHD2 transcript in cis, indicating bidirectional dosage sensitivity in human disease.
Sources: Literature
Intellectual disability v8.16 MARK2 Zornitza Stark gene: MARK2 was added
gene: MARK2 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: MARK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MARK2 were set to 39419027; 39436150
Phenotypes for gene: MARK2 were set to Neurodevelopmental disorder MONDO:0700092
Review for gene: MARK2 was set to GREEN
Added comment: 31 individuals with autism spectrum disorder (30/31), intellectual disability/developmental delay (100%), motor delay (62%), speech-language problems (100%), seizure/epilepsy (46%), behaviour disorders (ADHD, aggression, anxiety)(74%), and distinctive facial features (narrow face, abnormal or broad forehead, downslanting palpebral fissures, and large or dysplastic ears).

WES/WGS identified 25 LOF and 6 missense variants in MARK2 gene (Microtubule affinity-regulating kinase 2) which contributes to establishing neuronal polarity and developing dendritic spines. LOF variants were de novo (16/25), inherited (4/25), or unk (5/25). All 6 missense variants were de novo and clustered in the kinase or KA1 domains.

The mRNA and protein expression of MARK2 in PBMCs were significantly lower in affected individuals with LOF variants than in the control group. In vitro expression assay of missense variants supported the effect of MARK2 loss. Proband-derived and CRISPR-engineered isogenic induced pluripotent stem cells (iPSCs) showed MARK2 loss leads to early neuronal developmental and functional deficits, including anomalous polarity and disorganization in neural rosettes, as well as imbalanced proliferation and differentiation in neural progenitor cells (NPCs). Mark2+/- mice showed abnormal cortical formation and partition and ASD-like behaviour. Through the use of RNA sequencing (RNA-seq) and lithium treatment, they linked MARK2 loss to downregulation of the WNT/β-catenin signaling pathway and identified lithium as a potential drug for treating MARK2-associated ASD.
Sources: Literature
Intellectual disability v8.16 WDR83OS Zornitza Stark reviewed gene: WDR83OS: Rating: GREEN; Mode of pathogenicity: None; Publications: 39471804; Phenotypes: complex neurodevelopmental disorder MONDO:0100038; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.131 PNPT1 Zornitza Stark reviewed gene: PNPT1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Congenital myopathy v5.1 MB Zornitza Stark reviewed gene: MB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Primary immunodeficiency or monogenic inflammatory bowel disease v7.15 TNFSF9 Boaz Palterer gene: TNFSF9 was added
gene: TNFSF9 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: TNFSF9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNFSF9 were set to 35657354
Phenotypes for gene: TNFSF9 were set to EBV lymphoproliferation; smooth muscle tumors
Penetrance for gene: TNFSF9 were set to unknown
Review for gene: TNFSF9 was set to RED
Added comment: Fournier et al. described one patient with DiGeorge syndrome with a unique susceptibility to EBV with broad EBV infection and smooth muscle tumors. He was found to have a homozygous missense mutation (p.V140G) in TNFSF9 coding for CD137L/4-1BBL, the ligand of the T cell co-stimulatory molecule CD137/4-1BB, whose deficiency predisposes to EBV infection.

They show that CD137LV140G mutant was weakly expressed on patient cells or when ectopically expressed in HEK and P815 cells. Importantly, patient EBV-infected B cells failed to trigger the expansion of EBV-specific T cells, resulting in decreased T cell effector responses. T cell expansion was recovered when CD137L expression was restored on B cells.
Sources: Literature
Adult onset neurodegenerative disorder v7.5 RAB32 Achchuthan Shanmugasundram Classified gene: RAB32 as Amber List (moderate evidence)
Adult onset neurodegenerative disorder v7.5 RAB32 Achchuthan Shanmugasundram Added comment: Comment on list classification: Although all reported cases were identified with the same p.Ser71Arg variant, there is functional evidence available for this variant. Hence, this gene can be promoted to green rating in the next GMS update.
Adult onset neurodegenerative disorder v7.5 RAB32 Achchuthan Shanmugasundram Gene: rab32 has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v7.4 RAB32 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has been associated with relevant phenotype in OMIM (MIM #620923).
Adult onset neurodegenerative disorder v7.4 RAB32 Achchuthan Shanmugasundram Phenotypes for gene: RAB32 were changed from Parkinson’s disease to {Parkinson disease 26, autosomal dominant, susceptibility to}, OMIM:620923
Adult onset neurodegenerative disorder v7.3 RAB32 Achchuthan Shanmugasundram Publications for gene: RAB32 were set to PMID: 38858457
Adult onset neurodegenerative disorder v7.2 RAB32 Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: RAB32.
Adult onset neurodegenerative disorder v7.2 RAB32 Achchuthan Shanmugasundram reviewed gene: RAB32: Rating: GREEN; Mode of pathogenicity: None; Publications: 38614108, 38858457; Phenotypes: {Parkinson disease 26, autosomal dominant, susceptibility to}, OMIM:620923; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v7.15 IL27RA Achchuthan Shanmugasundram Classified gene: IL27RA as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v7.15 IL27RA Achchuthan Shanmugasundram Gene: il27ra has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v7.14 IL27RA Achchuthan Shanmugasundram changed review comment from: PMID:38509369 reported three children from two families with severe acute primary Epstein-Barr virus infection. One family was reported with a homozygous p.Gln96Ter variant and the other family was reported with compound heterozygous variants - an-inframe deletion of (p.Gln381_Ala395del) and a missense variant p.Arg446Gly. p.Arg446Gly was identified in homozygous state in 15 individuals from FinnGen database, which contains >400,000 individuals. Two of these individuals had hospital diagnoses of EBV infectious mononucleosis (IM). There is extensive ex vivo and in vitro data available, including mice model.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.; to: PMID:38509369 reported three children from two families with severe acute primary Epstein-Barr virus infection. One family was reported with a homozygous p.Gln96Ter variant and the other family was reported with compound heterozygous variants - an-inframe deletion of (p.Gln381_Ala395del) and a missense variant p.Arg446Gly. p.Arg446Gly was enriched in the Finnish population (minor allele frequency = 0.0068) and was identified in homozygous state in 15 individuals from FinnGen database, which contains >400,000 individuals. Two of these individuals had hospital diagnoses of EBV infectious mononucleosis (IM). There is extensive ex vivo and in vitro data available, including mice model.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.

The evidence available suggests that the rating should be borderline amber/ green due to functional data. Hence, the 'watchlist' tag has been added with amber rating.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.14 IL27RA Achchuthan Shanmugasundram Phenotypes for gene: IL27RA were changed from Severe EBV infection to Epstein-Barr virus infection, MONDO:0005111
Primary immunodeficiency or monogenic inflammatory bowel disease v7.13 IL27RA Achchuthan Shanmugasundram Tag watchlist tag was added to gene: IL27RA.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.13 IL27RA Achchuthan Shanmugasundram reviewed gene: IL27RA: Rating: AMBER; Mode of pathogenicity: None; Publications: 38509369; Phenotypes: Epstein-Barr virus infection, MONDO:0005111; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v7.13 TRAF3 Achchuthan Shanmugasundram Classified gene: TRAF3 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v7.13 TRAF3 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available now for the promotion of this gene to green rating in the next GMS update.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.13 TRAF3 Achchuthan Shanmugasundram Gene: traf3 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v7.12 TRAF3 Achchuthan Shanmugasundram Phenotypes for gene: TRAF3 were changed from Herpes simplex encephalitis, susceptibility to, 3; Defects in Intrinsic and Innate Immunity; {?Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 5},614849; Herpes simplex virus 1 encephalitis; Herpetic encephalitis (HSE); Defects in intrinsic and innate immunity to {?Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 5}, OMIM:614849; immune dysregulation, autoimmunity, and autoinflammation, MONDO:0957790
Primary immunodeficiency or monogenic inflammatory bowel disease v7.11 TRAF3 Achchuthan Shanmugasundram Publications for gene: TRAF3 were set to 24378539; 20832341; 32048120; 11296228; 32086639
Primary immunodeficiency or monogenic inflammatory bowel disease v7.10 TRAF3 Achchuthan Shanmugasundram Mode of inheritance for gene: TRAF3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v7.9 TRAF3 Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: TRAF3.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.9 TRAF3 Achchuthan Shanmugasundram reviewed gene: TRAF3: Rating: GREEN; Mode of pathogenicity: None; Publications: 35960817; Phenotypes: immune dysregulation, autoimmunity, and autoinflammation, MONDO:0957790; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v7.9 RELB Achchuthan Shanmugasundram Classified gene: RELB as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v7.9 RELB Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots, there is sufficient evidence available (four unrelated cases and functional work) for the promotion of this gene to green rating in the next GMS update.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.9 RELB Achchuthan Shanmugasundram Gene: relb has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v7.8 RELB Achchuthan Shanmugasundram Phenotypes for gene: RELB were changed from Recurrent infections; Recurrent infectionsImmunodeficiencies affecting cellular and humoral immunity; Immunodeficiencies affecting cellular and humoral immunity; ?Immunodeficiency 53, 617585 to ?Immunodeficiency 53, OMIM:617585
Primary immunodeficiency or monogenic inflammatory bowel disease v7.7 RELB Achchuthan Shanmugasundram Publications for gene: RELB were set to 26385063; 32086639; 32048120
Primary immunodeficiency or monogenic inflammatory bowel disease v7.6 RELB Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: RELB.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.6 RELB Achchuthan Shanmugasundram Deleted their comment
Primary immunodeficiency or monogenic inflammatory bowel disease v7.6 RELB Achchuthan Shanmugasundram commented on gene: RELB: PMID:26385063 reported three male patients from a related kindred with primary immunodeficiency and with a homozygous truncating variant in RELB (p.Tyr397Ter). All had recurrent upper and lower respiratory infections, one had ecthyma gangrenosum and developed a polyarticular arthritis with joint swelling, and another had a urinary tract infection.

PMID:36402602 reported three siblings presenting with predominately severe autoimmune manifestations involving the liver, gut, lung, and skin, as well as repeated infections. They were identified with homozygous p.Pro364Leu variant.

PMID:39231201 reported two unrelated adult patients with either homozygous (p.Q72Tfs*152) or compound heterozygous (p.Glu145Lys & p.Pro364Leu) loss-of-function variants. Both of them presented with combined immunodeficiency with early-onset severe bacterial, viral, and fungal diseases.

Functional evidence is also available from all three publications mentioned above.

This gene has been associated with immunodeficiency phenotype in OMIM (MIM #617585).
Primary immunodeficiency or monogenic inflammatory bowel disease v7.6 RELB Achchuthan Shanmugasundram reviewed gene: RELB: Rating: GREEN; Mode of pathogenicity: None; Publications: 26385063, 36402602, 39231201; Phenotypes: ?Immunodeficiency 53, OMIM:617585; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Congenital myopathy v5.1 MB Cassandra Smith gene: MB was added
gene: MB was added to Congenital myopathy. Sources: Other
Mode of inheritance for gene: MB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MB were set to 30918256; 35527200; 34679218
Review for gene: MB was set to GREEN
Added comment: Seven unrelated families reported in the literature with the same His98Tyr variant, with haplotype analysis for six of these families suggesting a recurrent variant on different backgrounds.
Sources: Other
Respiratory ciliopathies including non-CF bronchiectasis v3.19 TAPT1 Steven Cowman reviewed gene: TAPT1: Rating: RED; Mode of pathogenicity: None; Publications: 26365339; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Arthrogryposis v8.4 MET Achchuthan Shanmugasundram Classified gene: MET as Amber List (moderate evidence)
Arthrogryposis v8.4 MET Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Dmitrijs Rots, two unrelated cases and functional evidence are available in support of the disease association. Hence, this gene can be promoted to green rating in the next GMS update.
Arthrogryposis v8.4 MET Achchuthan Shanmugasundram Gene: met has been classified as Amber List (Moderate Evidence).
Arthrogryposis v8.3 MET Achchuthan Shanmugasundram Phenotypes for gene: MET were changed from Arthrogryposis to ?Arthrogryposis, distal, type 11, OMIM:620019
Arthrogryposis v8.2 MET Achchuthan Shanmugasundram Publications for gene: MET were set to PMID: 38429387; 30777867
Arthrogryposis v8.1 MET Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: MET.
Arthrogryposis v8.1 MET Achchuthan Shanmugasundram reviewed gene: MET: Rating: GREEN; Mode of pathogenicity: None; Publications: 30777867, 38429387; Phenotypes: ?Arthrogryposis, distal, type 11, OMIM:620019; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v7.6 IL7 Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: IL7.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.6 IL7 Achchuthan Shanmugasundram Classified gene: IL7 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v7.6 IL7 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Cassandra Smith, PMID:39352394 reported the identification of biallelic IL7 variants in four unrelated kindreds with combined immunodeficiency and recurrent infections. Extensive immunophenotyping revealed IL7 dependent and independent development of T cells.

As there is sufficient evidence available, this gene should be promoted to green rating in the next GMS update.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.6 IL7 Achchuthan Shanmugasundram Gene: il7 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v7.5 IL7 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has not yet been associated with immunodeficiency phenotype either in OMIM or in Gene2Phenotype.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.5 IL7 Achchuthan Shanmugasundram Phenotypes for gene: IL7 were changed from to combined immunodeficiency, MONDO:0015131
Primary immunodeficiency or monogenic inflammatory bowel disease v7.4 IL7 Achchuthan Shanmugasundram reviewed gene: IL7: Rating: GREEN; Mode of pathogenicity: None; Publications: 39352394; Phenotypes: combined immunodeficiency, MONDO:0015131; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.16 CCDC88A Arina Puzriakova Publications for gene: CCDC88A were set to 26917597
Early onset or syndromic epilepsy v7.6 CCDC88A Arina Puzriakova Publications for gene: CCDC88A were set to 26917597; 30392057
Intellectual disability v8.15 CCDC88A Arina Puzriakova Phenotypes for gene: CCDC88A were changed from PEHO syndrome to PEHO syndrome-like, OMIM:617507
Severe microcephaly v7.4 CCDC88A Arina Puzriakova Publications for gene: CCDC88A were set to 26917597; 30392057
Early onset or syndromic epilepsy v7.5 CCDC88A Arina Puzriakova Phenotypes for gene: CCDC88A were changed from ?PEHO syndrome-like 617507 to PEHO syndrome-like, OMIM:617507
Severe microcephaly v7.3 CCDC88A Arina Puzriakova Phenotypes for gene: CCDC88A were changed from PEHO syndrome-like, 617507; microcephaly to PEHO syndrome-like, OMIM:617507
Early onset or syndromic epilepsy v7.4 CCDC88A Arina Puzriakova Tag watchlist was removed from gene: CCDC88A.
Tag Q3_24_promote_green tag was added to gene: CCDC88A.
Intellectual disability v8.14 CCDC88A Arina Puzriakova Classified gene: CCDC88A as Amber List (moderate evidence)
Intellectual disability v8.14 CCDC88A Arina Puzriakova Added comment: Comment on list classification: There are now at least 7 individuals from 4 unrelated families with biallelic variants in the CCDC88A gene (PMID: 26917597; 30392057; 37798908; 39334473), described to a PEHO-like syndrome with universal features including ID, epilepsy, microcephaly and optic nerve/cerebellar atrophy.

Sufficient unrelated cases with the same phenotype to promote this gene to green at the next GMS panel update.
Intellectual disability v8.14 CCDC88A Arina Puzriakova Gene: ccdc88a has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.13 CCDC88A Arina Puzriakova Tag Q3_24_promote_green tag was added to gene: CCDC88A.
Early onset or syndromic epilepsy v7.4 CCDC88A Arina Puzriakova Classified gene: CCDC88A as Amber List (moderate evidence)
Early onset or syndromic epilepsy v7.4 CCDC88A Arina Puzriakova Added comment: Comment on list classification: There are now at least 7 individuals from 4 unrelated families with biallelic variants in the CCDC88A gene (PMID: 26917597; 30392057; 37798908; 39334473), described to a PEHO-like syndrome with universal features including ID, epilepsy, microcephaly and optic nerve/cerebellar atrophy.

Sufficient unrelated cases with the same phenotype to promote this gene to green at the next GMS panel update.
Early onset or syndromic epilepsy v7.4 CCDC88A Arina Puzriakova Gene: ccdc88a has been classified as Amber List (Moderate Evidence).
Severe microcephaly v7.2 CCDC88A Arina Puzriakova Classified gene: CCDC88A as Amber List (moderate evidence)
Severe microcephaly v7.2 CCDC88A Arina Puzriakova Added comment: Comment on list classification: There are now at least 7 individuals from 4 unrelated families with biallelic variants in the CCDC88A gene (PMID: 26917597; 30392057; 37798908; 39334473), described to a PEHO-like syndrome with universal features including ID, epilepsy, microcephaly and optic nerve/cerebellar atrophy.

Sufficient unrelated cases with the same phenotype to promote this gene to green at the next GMS panel update.
Severe microcephaly v7.2 CCDC88A Arina Puzriakova Gene: ccdc88a has been classified as Amber List (Moderate Evidence).
Severe microcephaly v7.1 CCDC88A Arina Puzriakova Tag Q3_24_promote_green tag was added to gene: CCDC88A.
Hereditary neuropathy or pain disorder v6.131 SPAST Arina Puzriakova Classified gene: SPAST as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.131 SPAST Arina Puzriakova Added comment: Comment on list classification: Axonal peripheral polyneuropathy was reported in at least 8 individuals with SPAST-related HSP (PMID:28572275) and has been recommended for this panel by Alex Rossor (UCL). The scope of this panel has now been expanded to include complex forms of neuropathy and therefore this gene can be promoted to Green at the next GMS panel update.
Hereditary neuropathy or pain disorder v6.131 SPAST Arina Puzriakova Gene: spast has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.130 OPA3 Eleanor Williams Phenotypes for gene: OPA3 were changed from Infantile optic atrophy, additionally, extra pyramidal disorder (chorea), ataxia, cognitive defects, axonal sensory neuropathy, autonomic neuropathy, pseudo-obstruction; Optic atrophy 3 with cataract, 165300; 3-methylglutaconic aciduria, type III, 258501 to Optic atrophy 3 with cataract, OMIM:165300; optic atrophy 3, MONDO:0008133
Hereditary neuropathy or pain disorder v6.129 OPA3 Eleanor Williams Publications for gene: OPA3 were set to
Hereditary neuropathy or pain disorder v6.128 OPA3 Eleanor Williams Added comment: Comment on mode of inheritance: Cases with peripheral neuropathy appear to be associated with autosomal dominant Optic atrophy 3 with cataract. This gene is also associated with a recessive condition in OMIM.
Hereditary neuropathy or pain disorder v6.128 OPA3 Eleanor Williams Mode of inheritance for gene: OPA3 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary neuropathy or pain disorder v6.127 OPA3 Eleanor Williams Tag Q3_24_promote_green tag was added to gene: OPA3.
Tag Q3_24_NHS_review tag was added to gene: OPA3.
Hereditary neuropathy or pain disorder v6.127 OPA3 Eleanor Williams changed review comment from: Associated with 3-methylglutaconic aciduria, type III, OMIM:258501 (AR) and Optic atrophy 3 with cataract, OMIM:165300 (AD).

PMID:28050599 - Bourne et al 2017 - 1 case - woman with cataracts, optic atrophy, lipodystrophy/lipoatrophy, and peripheral neuropathy. Exome sequencing identified a OPA3 c.235C > G p.(Leu79Val) variant that was confirmed to be de novo. The variant is not reported in gnomAD.

PMID: 31119193 - Horga et al 2019 - describe 2 families and one sporadic case with a syndromic form of OPA3-related autosomal dominant optic atrophy and cataract in which patients also show peripheral neuropathy. Heterozyous variants in OPA3 were identified c.23T>C (p.Met8Thr), c.313C>G (p.Gln105Glu) and c.313C>G (p.Gln105Glu) in each of the 3 families. In In 4 patients, the peripheral neuropathy was a major cause of disability or was severe enough to motivate the referral to specialists.

PMID:21036400 - Yu-Wai-Man et al 2011 - no patients with OPA3 variants reported, only OPA1 variants.; to: Associated with 3-methylglutaconic aciduria, type III, OMIM:258501 (AR) and Optic atrophy 3 with cataract, OMIM:165300 (AD).

PMID:28050599 - Bourne et al 2017 - 1 case - woman with cataracts, optic atrophy, lipodystrophy/lipoatrophy, and peripheral neuropathy. Exome sequencing identified a OPA3 c.235C > G p.(Leu79Val) variant that was confirmed to be de novo. The variant is not reported in gnomAD.

PMID: 31119193 - Horga et al 2019 - describe 2 families and one sporadic case with a syndromic form of OPA3-related autosomal dominant optic atrophy and cataract in which patients also show peripheral neuropathy. Heterozyous variants in OPA3 were identified c.23T>C (p.Met8Thr), c.313C>G (p.Gln105Glu) and c.313C>G (p.Gln105Glu) in each of the 3 families. In 4 patients, the peripheral neuropathy was a major cause of disability or was severe enough to motivate the referral to specialists.

PMID:21036400 - Yu-Wai-Man et al 2011 - no patients with OPA3 variants reported, only OPA1 variants.
Hereditary neuropathy or pain disorder v6.127 OPA3 Eleanor Williams reviewed gene: OPA3: Rating: GREEN; Mode of pathogenicity: None; Publications: 28050599, 31119193; Phenotypes: Optic atrophy 3 with cataract, OMIM:165300; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary neuropathy or pain disorder v6.127 SPAST Arina Puzriakova Tag Q3_24_promote_green tag was added to gene: SPAST.
Tag Q3_24_NHS_review tag was added to gene: SPAST.
Hereditary neuropathy or pain disorder v6.127 PRNP Arina Puzriakova Classified gene: PRNP as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.127 PRNP Arina Puzriakova Added comment: Comment on list classification: Neuropathy (predominantly sensory and autonomic) has been reported in at least 7 unrelated families with PRNP-related prion disease, which can present as an early and/or isolated feature. The scope of this panel has now been expanded to include complex forms of neuropathy and therefore this gene can be promoted to Green at the next GMS panel update.
Hereditary neuropathy or pain disorder v6.127 PRNP Arina Puzriakova Gene: prnp has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.126 PRNP Arina Puzriakova Phenotypes for gene: PRNP were changed from to Creutzfeldt-Jakob disease, OMIM:123400; dementia; autonomic neuropathy; sensory neuropathy
Hereditary neuropathy or pain disorder v6.125 PRNP Arina Puzriakova Publications for gene: PRNP were set to 24224623
Hereditary neuropathy or pain disorder v6.124 PRNP Arina Puzriakova Tag Q3_24_promote_green tag was added to gene: PRNP.
Tag Q3_24_NHS_review tag was added to gene: PRNP.
Hereditary neuropathy or pain disorder v6.124 POLG Achchuthan Shanmugasundram Classified gene: POLG as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.124 POLG Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Alexander Rossor, peripheral neuropathy is a well-established feature of POLG disease and hence this gene should be promoted to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v6.124 POLG Achchuthan Shanmugasundram Gene: polg has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.123 POLG Achchuthan Shanmugasundram Phenotypes for gene: POLG were changed from sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO); Mitochondrial DNA depletion syndrome 4A (Alpers type); Cardiomyopathy; Progressive external ophthalmoplegia, autosomal recessive 1; Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE); Progressive external ophthalmoplegia, autosomal dominant 1; Mitochondrial DNA depletion syndrome 4B (MNGIE type) to Mitochondrial DNA depletion syndrome 4B (MNGIE type), OMIM:613662; Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE), OMIM:607459; Progressive external ophthalmoplegia, autosomal dominant 1, OMIM:157640; Progressive external ophthalmoplegia, autosomal recessive 1, OMIM:258450
Hereditary neuropathy or pain disorder v6.122 POLG Achchuthan Shanmugasundram Publications for gene: POLG were set to
Hereditary neuropathy or pain disorder v6.121 POLG Achchuthan Shanmugasundram edited their review of gene: POLG: Changed publications to: 12975295, 15534189, 19752458, 25281868, 33791913, 36703500, 38975049
Hereditary neuropathy or pain disorder v6.121 POLG Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: POLG.
Tag Q3_24_NHS_review tag was added to gene: POLG.
Hereditary neuropathy or pain disorder v6.121 POLG Achchuthan Shanmugasundram changed review comment from: PMID:25281868 reported 116 patients with genetically-defined mitochondrial disease and progressive external ophthalmoplegia, of which 16 patients had a large-fibre peripheral neuropathy. Eight of them were identified with biallelic PLOG variants and one of them was identified with POLG monoallelic variant.

PMID:33791913 reported a patient with sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO) and was identified with two novel missense variants. A systematic review of previous literature in this publication summarised a total of 35 distinct variants from POLG are reported in 63 patients with SANDO. All of them had the variants either in homozygous or compound heterozygous state.

PMID:36703500 reported gait disturbance related to sensory ataxia and oculomotor abnormalities in four patients with biallelic POLG variants. They all had sensory axonal neuropathy.

PMID:38975049 reported a retrospective study of 40 children carrying biallelic pathogenic POLG variants, of which sensorimotor axonal neuropathy was present in eight children (20%) and polyradiculoneuropathy was present in six children (15%).


; to: PMID:12975295 reported four unrelated patients with progressive external ophthalmoplegia (PEO) and with POLG variants. Of three patients with heterozygous variants, one had neuropathy and the only patient with compound heterozygous variants also had neuropathy.

PMID:15534189 reported a family with monoallelic missense variant in POLG gene and with progressive external ophthalmoplegia, neuropathy, hypogonadism, and parkinsonism.

PMID:19752458 reported 26 patients from 23 families with cerebellar ataxia plus sensory neuropathy or external ophthalmoplegia. Of these 15 patients from 11 families were identified with POLG variants, of which four patients from two families had heterozygous variants and 11 patients from nine families had either homozygous or compound heterozygous variants.

PMID:25281868 reported 116 patients with genetically-defined mitochondrial disease and progressive external ophthalmoplegia, of which 16 patients had a large-fibre peripheral neuropathy. Eight of them were identified with biallelic PLOG variants and one of them was identified with POLG monoallelic variant.

PMID:33791913 reported a patient with sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO) and was identified with two novel missense variants. A systematic review of previous literature in this publication summarised a total of 35 distinct variants from POLG are reported in 63 patients with SANDO. All of them had the variants either in homozygous or compound heterozygous state.

PMID:36703500 reported gait disturbance related to sensory ataxia and oculomotor abnormalities in four patients with biallelic POLG variants. They all had sensory axonal neuropathy.

PMID:38975049 reported a retrospective study of 40 children carrying biallelic pathogenic POLG variants, of which sensorimotor axonal neuropathy was present in eight children (20%) and polyradiculoneuropathy was present in six children (15%).

Both monoallelic and biallelic variants of this gene are associated with relevant phenotypes in OMIM and Gene2Phenotype (DD and eye panels) and OMIM records neuropathy as a clinical presentation of all but one phenotypes.
Hereditary neuropathy or pain disorder v6.121 TUBB3 Arina Puzriakova Publications for gene: TUBB3 were set to
Hereditary neuropathy or pain disorder v6.120 TUBB3 Arina Puzriakova Classified gene: TUBB3 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.120 TUBB3 Arina Puzriakova Added comment: Comment on list classification: Peripheral neuropathy has been reported >3 unrelated cases with CFEOM3A and one family with multiple mutant carriers had isolated peripheral neuropathy (PMID: 20074521). The scope of this panel has now been expanded to complex forms of neuropathy and therefore this gene can be promoted to Green at the next GMS panel update.
Hereditary neuropathy or pain disorder v6.120 TUBB3 Arina Puzriakova Gene: tubb3 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy v1.492 TUBB3 Arina Puzriakova Phenotypes for gene: TUBB3 were changed from Fibrosis of extraocular muscles, congenital, 3A; CFEOM3A; CONGENITAL FIBROSIS OF THE EXTRAOCULAR MUSCLES to Fibrosis of extraocular muscles, congenital, 3A, OMIM:600638; CFEOM3A
Hereditary neuropathy or pain disorder v6.119 TUBB3 Arina Puzriakova Phenotypes for gene: TUBB3 were changed from CONGENITAL FIBROSIS OF THE EXTRAOCULAR MUSCLES; CFEOM3A; Fibrosis of extraocular muscles, congenital, 3A to Fibrosis of extraocular muscles, congenital, 3A, OMIM:600638; CFEOM3A
Hereditary neuropathy or pain disorder v6.118 TUBB3 Arina Puzriakova Tag Q3_24_promote_green tag was added to gene: TUBB3.
Tag Q3_24_NHS_review tag was added to gene: TUBB3.
Hereditary neuropathy or pain disorder v6.118 POLG Achchuthan Shanmugasundram edited their review of gene: POLG: Changed publications to: 12975295, 25281868, 33791913, 36703500, 38975049; Changed phenotypes to: Mitochondrial DNA depletion syndrome 4B (MNGIE type), OMIM:613662, Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE), OMIM:607459, Progressive external ophthalmoplegia, autosomal dominant 1, OMIM:157640, Progressive external ophthalmoplegia, autosomal recessive 1, OMIM:258450
Likely inborn error of metabolism v7.2 TWNK Arina Puzriakova Phenotypes for gene: TWNK were changed from Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), OMIM:271245; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, OMIM:609286; Perrault syndrome 5, OMIM:616138 to Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), OMIM:271245 (AR); Perrault syndrome 5, OMIM:616138 (AR); Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, OMIM:609286 (AD)
Hereditary neuropathy v1.491 TWNK Arina Puzriakova Phenotypes for gene: TWNK were changed from Hereditary Neuropathies; Deafness, ovarian dysgenesis, learning difficulties, delayed motor development, cerebellar hypoplasia, peripheral axonal neuropathy to Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), OMIM:271245 (AR); Perrault syndrome 5, OMIM:616138 (AR); Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, OMIM:609286 (AD)
Undiagnosed metabolic disorders v1.624 TWNK Arina Puzriakova Phenotypes for gene: TWNK were changed from Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), OMIM:271245; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, OMIM:609286; Perrault syndrome 5, OMIM:616138 to Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), OMIM:271245 (AR); Perrault syndrome 5, OMIM:616138 (AR); Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, OMIM:609286 (AD)
Adult onset neurodegenerative disorder v7.2 TWNK Arina Puzriakova Phenotypes for gene: TWNK were changed from Spinocerebellar Ataxia, Recessive; Ataxia Neuropathy Spectrum Disorders, Dominant; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, 609286; Perrault syndrome 5, 616138; Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), 271245 to Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), OMIM:271245 (AR); Perrault syndrome 5, OMIM:616138 (AR); Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, OMIM:609286 (AD)
Hereditary ataxia v1.334 TWNK Arina Puzriakova Phenotypes for gene: TWNK were changed from Spinocerebellar Ataxia, Recessive; Ataxia Neuropathy Spectrum Disorders, Dominant; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, 609286; Perrault syndrome 5, 616138; Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), 271245 to Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), OMIM:271245 (AR); Perrault syndrome 5, OMIM:616138 (AR); Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, OMIM:609286 (AD)
Ataxia and cerebellar anomalies - narrow panel v7.4 TWNK Arina Puzriakova Phenotypes for gene: TWNK were changed from Spinocerebellar Ataxia, Recessive; Ataxia Neuropathy Spectrum Disorders, Dominant; Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, 609286; Perrault syndrome 5, 616138; Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), 271245 to Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), OMIM:271245 (AR); Perrault syndrome 5, OMIM:616138 (AR); Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, OMIM:609286 (AD)
Hereditary neuropathy or pain disorder v6.118 POLG Achchuthan Shanmugasundram edited their review of gene: POLG: Changed publications to: 25281868, 33791913, 36703500, 38975049; Changed phenotypes to: Mitochondrial DNA depletion syndrome 4B (MNGIE type), OMIM:613662, Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE), OMIM:607459'
Primary ovarian insufficiency v1.69 TWNK Arina Puzriakova Phenotypes for gene: TWNK were changed from Perrault syndrome 5, 616138 to Perrault syndrome 5, OMIM:616138
Hereditary neuropathy or pain disorder v6.118 POLG Achchuthan Shanmugasundram changed review comment from: PMID:25281868 reported 116 patients with genetically-defined mitochondrial disease and progressive external ophthalmoplegia, of which 16 patients had a large-fibre peripheral neuropathy. Eight of them were identified with biallelic PLOG variants and one of them was identified with POLG monoallelic variant.

PMID:33791913 reported a patient with sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO) and was identified with two novel missense variants. A systematic review of previous literature in this publication summarised a total of 35 distinct variants from POLG are reported in 63 patients with SANDO. All of them had the variants either in homozygous or compound heterozygous state.; to: PMID:25281868 reported 116 patients with genetically-defined mitochondrial disease and progressive external ophthalmoplegia, of which 16 patients had a large-fibre peripheral neuropathy. Eight of them were identified with biallelic PLOG variants and one of them was identified with POLG monoallelic variant.

PMID:33791913 reported a patient with sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO) and was identified with two novel missense variants. A systematic review of previous literature in this publication summarised a total of 35 distinct variants from POLG are reported in 63 patients with SANDO. All of them had the variants either in homozygous or compound heterozygous state.

PMID:36703500 reported gait disturbance related to sensory ataxia and oculomotor abnormalities in four patients with biallelic POLG variants. They all had sensory axonal neuropathy.

PMID:38975049 reported a retrospective study of 40 children carrying biallelic pathogenic POLG variants, of which sensorimotor axonal neuropathy was present in eight children (20%) and polyradiculoneuropathy was present in six children (15%).
Hereditary neuropathy or pain disorder v6.118 TWNK Arina Puzriakova Phenotypes for gene: TWNK were changed from Hereditary Neuropathies; Deafness, ovarian dysgenesis, learning difficulties, delayed motor development, cerebellar hypoplasia, peripheral axonal neuropathy to Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), OMIM:271245 (AR); Perrault syndrome 5, OMIM:616138 (AR); Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, OMIM:609286 (AD)
Hereditary neuropathy or pain disorder v6.117 TWNK Arina Puzriakova Publications for gene: TWNK were set to
Hereditary neuropathy or pain disorder v6.116 TWNK Arina Puzriakova Classified gene: TWNK as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.116 TWNK Arina Puzriakova Added comment: Comment on list classification: TWNK is associated with multiple phenotypes that feature peripheral neuropathy (Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), OMIM:271245 (AR); Perrault syndrome 5, OMIM:616138 (AR); Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, OMIM:609286 (AD)) - sufficient cases with dominant and recessive forms of disease to support the association.

The scope of this panel has now been expanded to complex forms of neuropathy and therefore this gene can be promoted to Green at the next GMS panel update.
Hereditary neuropathy or pain disorder v6.116 TWNK Arina Puzriakova Gene: twnk has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.115 TWNK Arina Puzriakova Tag Q3_24_promote_green tag was added to gene: TWNK.
Tag Q3_24_NHS_review tag was added to gene: TWNK.
Hereditary neuropathy or pain disorder v6.115 POLG Achchuthan Shanmugasundram reviewed gene: POLG: Rating: GREEN; Mode of pathogenicity: None; Publications: 25281868; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.115 XPA Arina Puzriakova Tag Q3_24_promote_green tag was added to gene: XPA.
Tag Q3_24_NHS_review tag was added to gene: XPA.
Hereditary neuropathy or pain disorder v6.115 XPA Arina Puzriakova Publications for gene: XPA were set to 2168777
Hereditary neuropathy or pain disorder v6.114 XPA Arina Puzriakova Classified gene: XPA as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.114 XPA Arina Puzriakova Added comment: Comment on list classification: Peripheral neuropathy is a reported feature in at least 8 unrelated families with xeroderma pigmentosum. The scope of this panel has now been expanded to complex forms of neuropathy and therefore this gene can be promoted to Green at the next GMS panel update.
Hereditary neuropathy or pain disorder v6.114 XPA Arina Puzriakova Gene: xpa has been classified as Amber List (Moderate Evidence).
Possible mitochondrial disorder - nuclear genes v3.111 MRPL39 Achchuthan Shanmugasundram Tag Q3_24_NHS_review was removed from gene: MRPL39.
Possible mitochondrial disorder - nuclear genes v3.111 MRPL39 Achchuthan Shanmugasundram Entity copied from Mitochondrial disorders v8.4
Possible mitochondrial disorder - nuclear genes v3.111 MRPL39 Achchuthan Shanmugasundram gene: MRPL39 was added
gene: MRPL39 was added to Possible mitochondrial disorder - nuclear genes. Sources: Literature,Expert Review Amber
Q3_24_promote_green, Q3_24_NHS_review tags were added to gene: MRPL39.
Mode of inheritance for gene: MRPL39 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MRPL39 were set to 37133451
Phenotypes for gene: MRPL39 were set to Combined oxidative phosphorylation deficiency 59, OMIM:620646
Mitochondrial disorders v8.4 MRPL39 Achchuthan Shanmugasundram Classified gene: MRPL39 as Amber List (moderate evidence)
Mitochondrial disorders v8.4 MRPL39 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Hannah Knight, there are three unrelated patients reported to be presenting with multisystem diseases with severity ranging from lethal, infantile-onset (Leigh syndrome spectrum) to milder with survival into adulthood. Two of these patients with more severe infantile-onset disease were identified with compound heterozygous frameshift variants in MRPL39 gene, while the third patient with milder disease was homozygous for a missense variant. There is also functional evidence available from patient fibroblasts.

As there is sufficient evidence available for the association of this gene with mitochondrial disease, this gene should be recommended for promotion to green rating in the next GMS update.
Mitochondrial disorders v8.4 MRPL39 Achchuthan Shanmugasundram Gene: mrpl39 has been classified as Amber List (Moderate Evidence).
Mitochondrial disorders v8.3 MRPL39 Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has been associated with relevant phenotype in OMIM (MIM #620646), but not yet in Gene2Phenotype.
Mitochondrial disorders v8.3 MRPL39 Achchuthan Shanmugasundram Phenotypes for gene: MRPL39 were changed from Combined oxidative phosphorylation deficiency 59 to Combined oxidative phosphorylation deficiency 59, OMIM:620646
Mitochondrial disorders v8.2 MRPL39 Achchuthan Shanmugasundram Publications for gene: MRPL39 were set to 37133451
Mitochondrial disorders v8.2 MRPL39 Achchuthan Shanmugasundram Publications for gene: MRPL39 were set to PMID: 37133451
Mitochondrial disorders v8.1 MRPL39 Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: MRPL39.
Tag Q3_24_NHS_review tag was added to gene: MRPL39.
Mitochondrial disorders v8.1 MRPL39 Achchuthan Shanmugasundram reviewed gene: MRPL39: Rating: GREEN; Mode of pathogenicity: None; Publications: 37133451; Phenotypes: Combined oxidative phosphorylation deficiency 59, OMIM:620646; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.113 SOX10 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available (more than six unrelated cases) for the association of monoallelic SOX10 variants with demyelinating peripheral neuropathy. Hence, this gene can be promoted to green rating on the next GMS update.; to: Comment on list classification: There is sufficient evidence available (more than six unrelated cases) for the association of monoallelic SOX10 variants with demyelinating peripheral neuropathy. Hence, this gene can be promoted to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v6.113 SOX10 Achchuthan Shanmugasundram Deleted their comment
Hereditary neuropathy or pain disorder v6.113 SOX10 Achchuthan Shanmugasundram Classified gene: SOX10 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.113 SOX10 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (more than six unrelated cases) for the association of monoallelic SOX10 variants with demyelinating peripheral neuropathy. Hence, this gene can be promoted to green rating on the next GMS update.
Hereditary neuropathy or pain disorder v6.113 SOX10 Achchuthan Shanmugasundram Gene: sox10 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.112 SOX10 Achchuthan Shanmugasundram Classified gene: SOX10 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.112 SOX10 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (more than six unrelated cases) for the association of monoallelic SOX10 variants with demyelinating peripheral neuropathy. Hence, this gene can be promoted to green rating on the next GMS update.
Hereditary neuropathy or pain disorder v6.112 SOX10 Achchuthan Shanmugasundram Gene: sox10 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.111 SOX10 Achchuthan Shanmugasundram Phenotypes for gene: SOX10 were changed from Waardenburg syndrome, type 2E, with or without neurologic involvement, 611584; Waardenburg syndrome, type 4C, 613266; PCWH syndrome, 609136; Hypopigmentation of the hair and skin, sensory hearing loss, demyelinating neuropathy, dysmyelinating leukodystrophy, developmental delay, spasticity, ataxia, Hirschsprung disease to PCWH syndrome, OMIM:609136
Hereditary neuropathy or pain disorder v6.110 SOX10 Achchuthan Shanmugasundram Publications for gene: SOX10 were set to 21898658
Hereditary neuropathy or pain disorder v6.109 SOX10 Achchuthan Shanmugasundram Mode of inheritance for gene: SOX10 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v6.108 SOX10 Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: SOX10.
Tag Q3_24_NHS_review tag was added to gene: SOX10.
Hereditary neuropathy or pain disorder v6.108 SOX10 Achchuthan Shanmugasundram reviewed gene: SOX10: Rating: GREEN; Mode of pathogenicity: None; Publications: 15004559, 29681101, 32150337; Phenotypes: PCWH syndrome, OMIM:609136; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v6.108 TTPA Sarah Leigh Tag Q3_24_promote_green tag was added to gene: TTPA.
Tag Q3_24_NHS_review tag was added to gene: TTPA.
Hereditary neuropathy or pain disorder v6.108 TTPA Sarah Leigh reviewed gene: TTPA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.108 TTPA Sarah Leigh Phenotypes for gene: TTPA were changed from Hereditary Neuropathies; Early onset ataxia and sensory axonal neuropathy similar to Friedreich ataxia, head titubation, normal fat absorption unlike abetalipoproteinaemia, rarely retinitis pigmentosa to Ataxia with isolated vitamin E deficiency, OMIM:277460; familial isolated deficiency of vitamin E MONDO:0010188
Hereditary neuropathy or pain disorder v6.107 TTPA Sarah Leigh Publications for gene: TTPA were set to
Hereditary neuropathy or pain disorder v6.106 GLA Sarah Leigh Tag Q3_24_promote_green tag was added to gene: GLA.
Tag Q3_24_NHS_review tag was added to gene: GLA.
Hereditary neuropathy or pain disorder v6.106 GLA Sarah Leigh reviewed gene: GLA: Rating: GREEN; Mode of pathogenicity: None; 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)
Hereditary neuropathy or pain disorder v6.106 GLA Sarah Leigh Phenotypes for gene: GLA were changed from Cardiomyopathy to Fabry disease, OMIM:301500; Fabry disease, cardiac variant, OMIM:301500; Fabry disease, MONDO:0010526
Hereditary neuropathy or pain disorder v6.105 GLA Sarah Leigh Publications for gene: GLA were set to
Hereditary neuropathy or pain disorder v6.104 FLVCR1 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: FLVCR1.
Tag Q3_24_NHS_review tag was added to gene: FLVCR1.
Hereditary neuropathy or pain disorder v6.104 FLVCR1 Sarah Leigh reviewed gene: FLVCR1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary neuropathy or pain disorder v6.104 FLVCR1 Sarah Leigh Phenotypes for gene: FLVCR1 were changed from Ataxia, posterior column, with retinitis pigmentosa, OMIM:609033 to Ataxia, posterior column, with retinitis pigmentosa, OMIM:609033; posterior column ataxia-retinitis pigmentosa syndrome, MONDO:0012177
Intellectual disability v8.13 SLC4A10 Cassandra Smith gene: SLC4A10 was added
gene: SLC4A10 was added to Intellectual disability. Sources: Other
Mode of inheritance for gene: SLC4A10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC4A10 were set to 37459438; 38054405
Review for gene: SLC4A10 was set to GREEN
Added comment: More than 10 families with biallelic variants reported in SLC4A10, causing a neurodevelopmental disorder including intellectual disability.
Sources: Other
Hereditary neuropathy or pain disorder v6.103 FLVCR1 Sarah Leigh Phenotypes for gene: FLVCR1 were changed from Ataxia, posterior column, with retinitis pigmentosa, 609033; Retinitis pigmentosa, sensory ganglionopathy and abnormal posterior columns on MRI to Ataxia, posterior column, with retinitis pigmentosa, OMIM:609033
Hereditary neuropathy or pain disorder v6.102 FLVCR1 Sarah Leigh Publications for gene: FLVCR1 were set to 21070897
Hereditary neuropathy or pain disorder v6.101 FAM126A Sarah Leigh Tag Q3_24_promote_green tag was added to gene: FAM126A.
Tag Q3_24_NHS_review tag was added to gene: FAM126A.
Hereditary neuropathy or pain disorder v6.101 FAM126A Sarah Leigh reviewed gene: FAM126A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.101 FAM126A Sarah Leigh Publications for gene: FAM126A were set to 16951682; 23998934; 21911699; 33531944; 22749724:
Hereditary neuropathy or pain disorder v6.100 AP1S1 Arina Puzriakova Publications for gene: AP1S1 were set to 19057675
Hereditary neuropathy or pain disorder v6.99 XPA Arina Puzriakova Phenotypes for gene: XPA were changed from Photosensitivity and increased risk of cutaneous malignancy, global developmental delay, deafness, sensory-motor axonal peripheral neuropathy; Xeroderma pigmentosum, group A, 278700 to Xeroderma pigmentosum, group A, OMIM:278700; Sensory-motor axonal peripheral neuropathy
Bilateral congenital or childhood onset cataracts v6.4 ADD3 Eleanor Williams gene: ADD3 was added
gene: ADD3 was added to Bilateral congenital or childhood onset cataracts. Sources: Literature
Mode of inheritance for gene: ADD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADD3 were set to 29768408
Phenotypes for gene: ADD3 were set to cataract, MONDO:0005129; Cataract, HP:0000518
Review for gene: ADD3 was set to RED
Added comment: PMID: 29768408 - Gonçalves et al 2018 reports 1 proband with childhood onset bilateral cataracts as part of a syndromic presentation including intellectual disability, microcephaly and skeletal defects. WES identified ADD3 compound heterozygous variants - c.86A>G, p.N29S; c.1588G>A, p.V530I (both on the same allele in the mother), c.995A>G, p.N332S (heterozygous in the father).

They also report an additional 3 siblings in another family with both ADD3 and KAT2B variants also presented with bilateral cataracts from early childhood along with further syndromic features of ID, skeletal defects, cardiac and renal abnormalities.
Sources: Literature
Hereditary neuropathy or pain disorder v6.98 PHYH Achchuthan Shanmugasundram Classified gene: PHYH as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.98 PHYH Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Alexander Rossor, peripheral neuropathy is a part of Refsum disease (MIM #266500). OMIM record lists peripheral sensorimotor neuropathy as one of the clinical manifestations. In addition, PMID:20301527 reports that polyneuropathy is present in ~70% of cases with Refsum disease.

Hence, this gene can be promoted to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v6.98 PHYH Achchuthan Shanmugasundram Gene: phyh has been classified as Amber List (Moderate Evidence).
Bilateral congenital or childhood onset cataracts v6.3 KAT2B Eleanor Williams changed review comment from: 1 case with homozygous variants in KAT2B with 2 siblings treated for bilateral cataracts in early childhood, along with a renal phenotype. An additional case where 3 siblings had bilateral cataracts either from birth or in early childhood but were an additional potentially pathogenic variant was found in the ADD gene.

PMID: 39366742 - Niel et al 2024 - 2 siblings originating from Montenegro who presented in teenage years with steroid-resistant nephrotic syndrome and had bilateral cataracts in early childhood. WES identified a homozygous variant in KAT2B in both patients (NM_003884.5:c.700dup, NP_003875.3:p.(Ser234LysfsTer13)), leading to a 1-base insertion, a frameshift and a premature stop codon in exon 6/18. The variant was not described in gnomAD, and was hetrozygous in both parents, who are unrelated but originate from the same geographical location in Montenegro. No pathogenic variants of other genes of interest, including ADD3 (previous cases with variants in both KAT2B and ADD and nephrotic syndrome have been reported PMID: 29768408), were identified.

PMID: 29768408 - Gonçalves et al 2018 - report 3 families with intellectual disability. Biallelic missense ADD variants were found in all probands, but in one family an additional homozygous variant (c.920T>C, p.F307S) was found in KAT2B. In this family, 3 affected siblings also presented with steroid-resistant nephrotic syndrome and proteinuira below the age of 13, dilated cardiomyopathy and bilateral cateracts. Bilateral cateracts were also reported in one of the probands with ADD variants only.
Sources: Literature; to: 1 case with homozygous variants in KAT2B with 2 siblings treated for bilateral cataracts in early childhood, along with a renal phenotype which develops later in childhood. An additional case where 3 siblings had bilateral cataracts either from birth or in early childhood but were an additional potentially pathogenic variant was found in the ADD gene.

PMID: 39366742 - Niel et al 2024 - 2 siblings originating from Montenegro who presented in teenage years with steroid-resistant nephrotic syndrome and had bilateral cataracts in early childhood. WES identified a homozygous variant in KAT2B in both patients (NM_003884.5:c.700dup, NP_003875.3:p.(Ser234LysfsTer13)), leading to a 1-base insertion, a frameshift and a premature stop codon in exon 6/18. The variant was not described in gnomAD, and was hetrozygous in both parents, who are unrelated but originate from the same geographical location in Montenegro. No pathogenic variants of other genes of interest, including ADD3 (previous cases with variants in both KAT2B and ADD and nephrotic syndrome have been reported PMID: 29768408), were identified.

PMID: 29768408 - Gonçalves et al 2018 - report 3 families with intellectual disability. Biallelic missense ADD variants were found in all probands, but in one family an additional homozygous variant (c.920T>C, p.F307S) was found in KAT2B. In this family, 3 affected siblings also presented with steroid-resistant nephrotic syndrome and proteinuira below the age of 13, dilated cardiomyopathy and bilateral cateracts. Bilateral cateracts were also reported in one of the probands with ADD variants only.
Sources: Literature
Bilateral congenital or childhood onset cataracts v6.3 KAT2B Eleanor Williams Classified gene: KAT2B as Red List (low evidence)
Bilateral congenital or childhood onset cataracts v6.3 KAT2B Eleanor Williams Added comment: Comment on list classification: Setting the rating as red, as only 1 case with cataracts and only KAT2B has been reported.
Bilateral congenital or childhood onset cataracts v6.3 KAT2B Eleanor Williams Gene: kat2b has been classified as Red List (Low Evidence).
Bilateral congenital or childhood onset cataracts v6.2 KAT2B Eleanor Williams gene: KAT2B was added
gene: KAT2B was added to Bilateral congenital or childhood onset cataracts. Sources: Literature
Mode of inheritance for gene: KAT2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KAT2B were set to 39366742; 29768408
Phenotypes for gene: KAT2B were set to cataract, MONDO:0005129; Cataract, HP:0000518
Review for gene: KAT2B was set to AMBER
Added comment: 1 case with homozygous variants in KAT2B with 2 siblings treated for bilateral cataracts in early childhood, along with a renal phenotype. An additional case where 3 siblings had bilateral cataracts either from birth or in early childhood but were an additional potentially pathogenic variant was found in the ADD gene.

PMID: 39366742 - Niel et al 2024 - 2 siblings originating from Montenegro who presented in teenage years with steroid-resistant nephrotic syndrome and had bilateral cataracts in early childhood. WES identified a homozygous variant in KAT2B in both patients (NM_003884.5:c.700dup, NP_003875.3:p.(Ser234LysfsTer13)), leading to a 1-base insertion, a frameshift and a premature stop codon in exon 6/18. The variant was not described in gnomAD, and was hetrozygous in both parents, who are unrelated but originate from the same geographical location in Montenegro. No pathogenic variants of other genes of interest, including ADD3 (previous cases with variants in both KAT2B and ADD and nephrotic syndrome have been reported PMID: 29768408), were identified.

PMID: 29768408 - Gonçalves et al 2018 - report 3 families with intellectual disability. Biallelic missense ADD variants were found in all probands, but in one family an additional homozygous variant (c.920T>C, p.F307S) was found in KAT2B. In this family, 3 affected siblings also presented with steroid-resistant nephrotic syndrome and proteinuira below the age of 13, dilated cardiomyopathy and bilateral cateracts. Bilateral cateracts were also reported in one of the probands with ADD variants only.
Sources: Literature
Proteinuric renal disease v4.20 KAT2B Eleanor Williams Classified gene: KAT2B as Amber List (moderate evidence)
Proteinuric renal disease v4.20 KAT2B Eleanor Williams Added comment: Comment on list classification: Promoting this gene to amber based on 1 case plus a second supportive case (with an additional possible variant) and a Drosophila model.
Proteinuric renal disease v4.20 KAT2B Eleanor Williams Gene: kat2b has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.97 PHYH Achchuthan Shanmugasundram Phenotypes for gene: PHYH were changed from Hereditary Neuropathies to Refsum disease, OMIM:266500
Hereditary neuropathy or pain disorder v6.96 PHYH Achchuthan Shanmugasundram Publications for gene: PHYH were set to
Hereditary neuropathy or pain disorder v6.95 PHYH Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: PHYH.
Tag Q3_24_NHS_review tag was added to gene: PHYH.
Hereditary neuropathy or pain disorder v6.95 PHYH Achchuthan Shanmugasundram reviewed gene: PHYH: Rating: GREEN; Mode of pathogenicity: None; Publications: 2433405, 9326940, 10767344, 20301527; Phenotypes: Refsum disease, OMIM:266500; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v4.19 KAT2B Eleanor Williams Phenotypes for gene: KAT2B were changed from Steroid-resistant nephrotic syndrome to steroid-resistant nephrotic syndrome, MONDO:0044765
Proteinuric renal disease v4.18 KAT2B Eleanor Williams Publications for gene: KAT2B were set to PMID: 39366742
Proteinuric renal disease v4.17 KAT2B Eleanor Williams Mode of inheritance for gene: KAT2B was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal
Proteinuric renal disease v4.16 KAT2B Eleanor Williams changed review comment from: 1 case reported of biallelic variants in KAT2B and steroid-resistant nephrotic syndrome. 2nd case with a similar phenotype but an additional variant ADD which may contribute to the patients phenotype.

PMID: 39366742 - Niel et al 2024 - 2 siblings originating from Montenegro who presented in teenage years with steroid-resistant nephrotic syndrome and had bilateral cataracts in early childhood. WES identified a homozygous variant in KAT2B in both patients (NM_003884.5:c.700dup, NP_003875.3:p.(Ser234LysfsTer13)), leading to a 1-base insertion, a frameshift and a premature stop codon in exon 6/18. The variant was not described in gnomAD, and was hetrozygous in both parents, who are unrelated but originate from the same geographical location in Montenegro. No pathogenic variants of other genes of interest, including ADD3 (previous cases with variants in both KAT2B and ADD and nephrotic syndrome have been reported PMID: 29768408), were identified.

PMID: 29768408 - Gonçalves et al 2018 - report 3 families with intellectual disability. Biallelic missense ADD variants were found in all probands, but in one family an additional homozygous variant (c.920T>C, p.F307S) was found in KAT2B. In this family, 3 affected siblings also presented with steroid-resistant nephrotic syndrome and proteinuira below the age of 13, dilated cardiomyopathy and bilateral cateracts. Bilateral cateracts were also reported in one of the probands with ADD variants only. In Drosophila KAT2B F307S mutants displayed both heart and renal defects will ADD mutants did not.; to: 1 case reported of biallelic variants in KAT2B and steroid-resistant nephrotic syndrome. 2nd case with a similar phenotype but an additional variant ADD which may contribute to the patients phenotype. Drosophila KAT2B mutant replicates the renal phenotype.

PMID: 39366742 - Niel et al 2024 - 2 siblings originating from Montenegro who presented in teenage years with steroid-resistant nephrotic syndrome and had bilateral cataracts in early childhood. WES identified a homozygous variant in KAT2B in both patients (NM_003884.5:c.700dup, NP_003875.3:p.(Ser234LysfsTer13)), leading to a 1-base insertion, a frameshift and a premature stop codon in exon 6/18. The variant was not described in gnomAD, and was hetrozygous in both parents, who are unrelated but originate from the same geographical location in Montenegro. No pathogenic variants of other genes of interest, including ADD3 (previous cases with variants in both KAT2B and ADD and nephrotic syndrome have been reported PMID: 29768408), were identified.

PMID: 29768408 - Gonçalves et al 2018 - report 3 families with intellectual disability. Biallelic missense ADD variants were found in all probands, but in one family an additional homozygous variant (c.920T>C, p.F307S) was found in KAT2B. In this family, 3 affected siblings also presented with steroid-resistant nephrotic syndrome and proteinuira below the age of 13, dilated cardiomyopathy and bilateral cateracts. Bilateral cateracts were also reported in one of the probands with ADD variants only. In Drosophila KAT2B F307S mutants displayed both heart and renal defects will ADD mutants did not.
Proteinuric renal disease v4.16 KAT2B Eleanor Williams reviewed gene: KAT2B: Rating: AMBER; Mode of pathogenicity: None; Publications: 39366742, 29768408; Phenotypes: steroid-resistant nephrotic syndrome, MONDO:0044765; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.95 HADHB Achchuthan Shanmugasundram Classified gene: HADHB as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.95 HADHB Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Alexander Rossor, mitochondrial trifunctional protein deficiency 2 (MIM #620300) includes peripheral neuropathy as one of the clinical manifestations. There are more than three unrelated cases reported with neuropathy in literature. Hence, this gene can be promoted to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v6.95 HADHB Achchuthan Shanmugasundram Gene: hadhb has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.94 HADHB Achchuthan Shanmugasundram Phenotypes for gene: HADHB were changed from Trifunctional protein deficiency, 609015 to Mitochondrial trifunctional protein deficiency 2, OMIM: 620300
Hereditary neuropathy or pain disorder v6.93 HADHB Achchuthan Shanmugasundram Publications for gene: HADHB were set to
Hereditary neuropathy or pain disorder v6.92 HADHB Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: HADHB.
Tag Q3_24_NHS_review tag was added to gene: HADHB.
Hereditary neuropathy or pain disorder v6.92 HADHB Achchuthan Shanmugasundram reviewed gene: HADHB: Rating: GREEN; Mode of pathogenicity: None; Publications: 24664533, 28685493, 28649548, 35235001, 37388542; Phenotypes: Mitochondrial trifunctional protein deficiency 2, OMIM: 620300; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.92 FAM126A Sarah Leigh Publications for gene: FAM126A were set to 16951682
Hereditary neuropathy or pain disorder v6.91 FAM126A Sarah Leigh Phenotypes for gene: FAM126A were changed from Congenital cataracts, global developmental delay from 1 year, diffuse cerebral hypomyelination on MRI, neuropathy with SNCV; Leukodystrophy, hypomyelinating, 5, 610532 to Leukodystrophy, hypomyelinating, 5, OMIM:610532; hypomyelinating leukodystrophy 5, MONDO:0012514
Hereditary neuropathy or pain disorder v6.90 FAH Sarah Leigh Tag Q3_24_promote_green tag was added to gene: FAH.
Tag Q3_24_NHS_review tag was added to gene: FAH.
Hereditary neuropathy or pain disorder v6.90 FAH Sarah Leigh reviewed gene: FAH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.90 HADHA Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: HADHA.
Tag Q3_24_NHS_review tag was added to gene: HADHA.
Hereditary neuropathy or pain disorder v6.90 HADHA Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by by Alexander Rossor, mitochondrial trifunctional protein deficiency 1 (MIM #609015) includes peripheral neuropathy as one of the clinical manifestations. There are at least three unrelated cases reported with neuropathy in literature. Hence, this gene can be promoted to green rating in the next GMS update.; to: Comment on list classification: As reviewed by Alexander Rossor, mitochondrial trifunctional protein deficiency 1 (MIM #609015) includes peripheral neuropathy as one of the clinical manifestations. There are at least three unrelated cases reported with neuropathy in literature. Hence, this gene can be promoted to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v6.90 FAH Sarah Leigh Phenotypes for gene: FAH were changed from Tyrosinemia, type I, OMIM:276700 to Tyrosinemia, type I, OMIM:276700; tyrosinemia type I, MONDO:0010161
Hereditary neuropathy or pain disorder v6.89 FAH Sarah Leigh Phenotypes for gene: FAH were changed from Infantile or adolescent onset liver disease, renal tubular dysfunction and hypophosphatemic rickets. Acute episodes of neuropathy similar to AIP; Tyrosinemia, type I, 276700 to Tyrosinemia, type I, OMIM:276700
Hereditary neuropathy or pain disorder v6.88 HADHA Achchuthan Shanmugasundram Classified gene: HADHA as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.88 HADHA Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by by Alexander Rossor, mitochondrial trifunctional protein deficiency 1 (MIM #609015) includes peripheral neuropathy as one of the clinical manifestations. There are at least three unrelated cases reported with neuropathy in literature. Hence, this gene can be promoted to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v6.88 HADHA Achchuthan Shanmugasundram Gene: hadha has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.87 HADHA Achchuthan Shanmugasundram Publications for gene: HADHA were set to
Hereditary neuropathy or pain disorder v6.86 HADHA Achchuthan Shanmugasundram Phenotypes for gene: HADHA were changed from Trifunctional protein deficiency, 609015 to Mitochondrial trifunctional protein deficiency 1, OMIM:609015
Hereditary neuropathy or pain disorder v6.85 HADHA Achchuthan Shanmugasundram reviewed gene: HADHA: Rating: GREEN; Mode of pathogenicity: None; Publications: 23868323, 32897397; Phenotypes: Mitochondrial trifunctional protein deficiency 1, OMIM:609015; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.85 FAH Sarah Leigh Publications for gene: FAH were set to
Early onset or syndromic epilepsy v7.3 PI4K2A Achchuthan Shanmugasundram Classified gene: PI4K2A as Amber List (moderate evidence)
Early onset or syndromic epilepsy v7.3 PI4K2A Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Tracy Lester, there are four unrelated cases reported with a neurodevelopmental disorder. Of these, epilepsy was present in three unrelated cases. Hence, this gene should be promoted to green rating in the next GMS update.
Early onset or syndromic epilepsy v7.3 PI4K2A Achchuthan Shanmugasundram Gene: pi4k2a has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v7.2 PI4K2A Achchuthan Shanmugasundram Deleted their comment
Early onset or syndromic epilepsy v7.2 PI4K2A Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Tracy Lester, there are four unrelated cases reported with global developmental delay and/ or profound intellectual disability. Hence, this gene should be promoted to green rating in the next GMS update.; to: Comment on list classification: As reviewed by Tracy Lester, there are four unrelated cases reported with a neurodevelopmental disorder . Hence, this gene should be promoted to green rating in the next GMS update.
Early onset or syndromic epilepsy v7.2 PI4K2A Achchuthan Shanmugasundram Entity copied from Intellectual disability v8.13
Early onset or syndromic epilepsy v7.2 PI4K2A Achchuthan Shanmugasundram gene: PI4K2A was added
gene: PI4K2A was added to Early onset or syndromic epilepsy. Sources: Expert Review Amber,NHS GMS
Q3_24_promote_green, Q3_24_NHS_review tags were added to gene: PI4K2A.
Mode of inheritance for gene: PI4K2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PI4K2A were set to 30564627; 32418222; 35880319
Phenotypes for gene: PI4K2A were set to Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities, OMIM:620732
Penetrance for gene: PI4K2A were set to unknown
Intellectual disability v8.13 PI4K2A Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v8.13 PI4K2A Achchuthan Shanmugasundram Classified gene: PI4K2A as Amber List (moderate evidence)
Intellectual disability v8.13 PI4K2A Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Tracy Lester, there are four unrelated cases reported with global developmental delay and/ or profound intellectual disability. Hence, this gene should be promoted to green rating in the next GMS update.
Intellectual disability v8.13 PI4K2A Achchuthan Shanmugasundram Gene: pi4k2a has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.13 PI4K2A Achchuthan Shanmugasundram Classified gene: PI4K2A as Amber List (moderate evidence)
Intellectual disability v8.13 PI4K2A Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Tracy Lester, there are four unrelated cases reported with global developmental delay and/ or profound intellectual disability. Hence, this gene should be promoted to green rating in the next GMS update.
Intellectual disability v8.13 PI4K2A Achchuthan Shanmugasundram Gene: pi4k2a has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.12 PI4K2A Achchuthan Shanmugasundram Added comment: Comment on phenotypes: This gene has been associated with relevant phenotype in OMIM (MIM #620732), but not yet in Gene2Phenotype.
Intellectual disability v8.12 PI4K2A Achchuthan Shanmugasundram Phenotypes for gene: PI4K2A were changed from Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities, OMIM:620732 to Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities, OMIM:620732
Intellectual disability v8.11 PI4K2A Achchuthan Shanmugasundram Phenotypes for gene: PI4K2A were changed from Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities, OMIM:620732 to Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities, OMIM:620732
Intellectual disability v8.11 PI4K2A Achchuthan Shanmugasundram Phenotypes for gene: PI4K2A were changed from Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities, OMIM:620732 to Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities, OMIM:620732
Intellectual disability v8.10 PI4K2A Achchuthan Shanmugasundram Phenotypes for gene: PI4K2A were changed from Intellectual disability; developmental delay; seizures to Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities, OMIM:620732
Intellectual disability v8.10 PI4K2A Achchuthan Shanmugasundram Publications for gene: PI4K2A were set to 30564627; 32418222'
Intellectual disability v8.10 PI4K2A Achchuthan Shanmugasundram Publications for gene: PI4K2A were set to 30564627; 35880319; 32418222
Intellectual disability v8.9 PI4K2A Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: PI4K2A.
Tag Q3_24_NHS_review tag was added to gene: PI4K2A.
Intellectual disability v8.9 PI4K2A Achchuthan Shanmugasundram reviewed gene: PI4K2A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hyperkinetic movements, seizures and structural brain abnormalities, OMIM:620732; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.84 SLC13A3 Achchuthan Shanmugasundram Phenotypes for gene: SLC13A3 were changed from acute neuropathy to Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate, OMIM:618384
Hereditary neuropathy or pain disorder v6.83 SLC13A3 Achchuthan Shanmugasundram edited their review of gene: SLC13A3: Changed phenotypes to: Leukoencephalopathy, acute reversible, with increased urinary alpha-ketoglutarate, OMIM:618384
Hereditary neuropathy or pain disorder v6.83 SLC13A3 Achchuthan Shanmugasundram Classified gene: SLC13A3 as Red List (low evidence)
Hereditary neuropathy or pain disorder v6.83 SLC13A3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Alexander Rossor, there is only case reported with neuropathy. Hence, this gene should be rated red with current evidence.
Hereditary neuropathy or pain disorder v6.83 SLC13A3 Achchuthan Shanmugasundram Gene: slc13a3 has been classified as Red List (Low Evidence).
Hereditary neuropathy or pain disorder v6.82 SLC13A3 Achchuthan Shanmugasundram reviewed gene: SLC13A3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.9 ZFYVE26 Arina Puzriakova Phenotypes for gene: ZFYVE26 were changed from SPASTIC PARAPLEGIA AUTOSOMAL RECESSIVE TYPE 15 (SPG15) to Spastic paraplegia 15, autosomal recessive, OMIM:270700
Hereditary neuropathy or pain disorder v6.82 ZFYVE26 Arina Puzriakova Phenotypes for gene: ZFYVE26 were changed from Hereditary Neuropathies; Onset second decade, spastic paraplegia, intellectual disability and cognitive decline, thin corpus callosum, mild cerebellar eye signs, axonal sensory-motor neuropathy, parkinsonism and dystonia, pseudobulbar involvement and pigmentry maculopathy; Spastic paraplegia 15, autosomal recessive, 270700 to Spastic paraplegia 15, autosomal recessive, OMIM:270700
Hereditary ataxia with onset in adulthood v7.2 ZFYVE26 Arina Puzriakova Phenotypes for gene: ZFYVE26 were changed from Autosomal recessive spastic paraplegia 15, 270700; Autosomal recessive spastic paraplegia 15, 270700 to Spastic paraplegia 15, autosomal recessive, OMIM:270700
Hereditary neuropathy v1.490 ZFYVE26 Arina Puzriakova Phenotypes for gene: ZFYVE26 were changed from Spastic paraplegia 15, autosomal recessive, 270700; Hereditary Neuropathies; Onset second decade, spastic paraplegia, intellectual disability and cognitive decline, thin corpus callosum, mild cerebellar eye signs, axonal sensory-motor neuropathy, parkinsonism and dystonia, pseudobulbar involvement and pigmentry maculopathy to Spastic paraplegia 15, autosomal recessive, OMIM:270700
Adult onset hereditary spastic paraplegia v5.3 ZFYVE26 Arina Puzriakova Phenotypes for gene: ZFYVE26 were changed from Spastic paraplegia 15, autosomal recessive, 270700 to Spastic paraplegia 15, autosomal recessive, OMIM:270700
Childhood onset hereditary spastic paraplegia v7.2 ZFYVE26 Arina Puzriakova Phenotypes for gene: ZFYVE26 were changed from Spastic paraplegia 15, autosomal recessive, 270700 to Spastic paraplegia 15, autosomal recessive, OMIM:270700
Hereditary spastic paraplegia v1.312 ZFYVE26 Arina Puzriakova Phenotypes for gene: ZFYVE26 were changed from Spastic paraplegia 15, autosomal recessive to Spastic paraplegia 15, autosomal recessive, OMIM:270700
Hereditary neuropathy or pain disorder v6.81 ZFYVE26 Arina Puzriakova Publications for gene: ZFYVE26 were set to
Intellectual disability v8.8 KIF5B Achchuthan Shanmugasundram changed review comment from: Comment on list classification: Although ID was reported in four of seven cases, all these patients display complex syndromic disease with broad spectrum of phenotypes and the severity of ID was mild in one and not reported in two others. This gene has been added with green rating on the DDG2P panel and hence will be included in the paediatric disorders super panel.

Hence, this gene should be rated amber with current evidence. The 'watchlist' tag has been added to keep track new evidence.; to: Comment on list classification: Although ID was reported in four of seven cases, all these patients display complex syndromic disease with broad spectrum of phenotypes and the severity of ID was mild in one and not reported in two others. This gene has been added with green rating on the DDG2P panel and hence will be included in the paediatric disorders super panel.

Hence, this gene should be rated amber with current evidence. The 'watchlist' tag has been added to keep track of new evidence.
Intellectual disability v8.8 KIF5B Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v8.8 KIF5B Achchuthan Shanmugasundram Classified gene: KIF5B as Amber List (moderate evidence)
Intellectual disability v8.8 KIF5B Achchuthan Shanmugasundram Added comment: Comment on list classification: Although ID was reported in four of seven cases, all these patients display complex syndromic disease with broad spectrum of phenotypes and the severity of ID was mild in one and not reported in two others. This gene has been added with green rating on the DDG2P panel and hence will be included in the paediatric disorders super panel.

Hence, this gene should be rated amber with current evidence. The 'watchlist' tag has been added to keep track new evidence.
Intellectual disability v8.8 KIF5B Achchuthan Shanmugasundram Gene: kif5b has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.8 KIF5B Achchuthan Shanmugasundram Classified gene: KIF5B as Amber List (moderate evidence)
Intellectual disability v8.8 KIF5B Achchuthan Shanmugasundram Added comment: Comment on list classification: Although ID was reported in four of seven cases, all these patients display complex syndromic disease with broad spectrum of phenotypes and the severity of ID was mild in one and not reported in two others. This gene has been added with green rating on the DDG2P panel and hence will be included in the paediatric disorders super panel.

Hence, this gene should be rated amber with current evidence. The 'watchlist' tag has been added to keep track new evidence.
Intellectual disability v8.8 KIF5B Achchuthan Shanmugasundram Gene: kif5b has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.7 KIF5B Achchuthan Shanmugasundram Tag watchlist tag was added to gene: KIF5B.
Intellectual disability v8.7 KIF5B Achchuthan Shanmugasundram Phenotypes for gene: KIF5B were changed from kyphomelic dysplasia; hypotonia; developmental delay; intellectual disability to kyphomelic dysplasia, MONDO:0008881; intellectual disability, MONDO:0001071
Intellectual disability v8.6 KIF5B Achchuthan Shanmugasundram changed review comment from: As reviewed by Tracy Lester, there are a total of seven patients reported with missense variants in KIF5B gene from PMIDs: 35342932 and 36018820. Four of these seven patients presented with intellectual disability (two each from the two studies).

This gene has been associated with relevant phenotype in Gene2Phenotype (with 'moderate' rating on the DD panel), but not yet in OMIM.; to: As reviewed by Tracy Lester, there are a total of seven patients reported with missense variants in KIF5B gene from PMIDs: 35342932 and 36018820. Four of these seven patients presented with intellectual disability (two each from the two studies). PMID:36018820 reported the severity of ID as severe for one patient and mild for another, while severity was not recoded in PMID:35342932.

This gene has been associated with relevant phenotype in Gene2Phenotype (with 'moderate' rating on the DD panel), but not yet in OMIM.
Hereditary neuropathy or pain disorder v6.80 ZFYVE26 Arina Puzriakova Classified gene: ZFYVE26 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.80 ZFYVE26 Arina Puzriakova Added comment: Comment on list classification: Peripheral neuropathy is a reported feature in at least 5 unrelated families with SPG15. The scope of this panel has now been expanded to complex forms of neuropathy and therefore this gene can be promoted to Green at the next GMS panel update.
Hereditary neuropathy or pain disorder v6.80 ZFYVE26 Arina Puzriakova Gene: zfyve26 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.6 KIF5B Achchuthan Shanmugasundram reviewed gene: KIF5B: Rating: AMBER; Mode of pathogenicity: None; Publications: 35342932, 36018820; Phenotypes: kyphomelic dysplasia, MONDO:0008881, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v6.79 ZFYVE26 Arina Puzriakova Tag Q3_24_promote_green tag was added to gene: ZFYVE26.
Tag Q3_24_NHS_review tag was added to gene: ZFYVE26.
Hereditary neuropathy or pain disorder v6.79 SAMD9L Eleanor Williams Classified gene: SAMD9L as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.79 SAMD9L Eleanor Williams Added comment: Comment on list classification: Promoting to amber with a recommendation for green rating following GMS review.
Hereditary neuropathy or pain disorder v6.79 SAMD9L Eleanor Williams Gene: samd9l has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.78 SAMD9L Eleanor Williams Publications for gene: SAMD9L were set to ataxia; peripheral neuropathy; pancytopenia
Hereditary neuropathy or pain disorder v6.77 SAMD9L Eleanor Williams Phenotypes for gene: SAMD9L were changed from 32808377: 36553623 : 31053103: 27259050: 28202457 to Ataxia-pancytopenia syndrome, OMIM:159550; ataxia-pancytopenia syndrome, MONDO:0008038
Hereditary neuropathy or pain disorder v6.76 SAMD9L Eleanor Williams Mode of pathogenicity for gene: SAMD9L 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
Hereditary neuropathy or pain disorder v6.75 SAMD9L Eleanor Williams Tag missense tag was added to gene: SAMD9L.
Tag mosaicism tag was added to gene: SAMD9L.
Tag Q3_24_promote_green tag was added to gene: SAMD9L.
Tag Q3_24_NHS_review tag was added to gene: SAMD9L.
Hereditary neuropathy or pain disorder v6.75 SAMD9L Eleanor Williams edited their review of gene: SAMD9L: Changed rating: GREEN; Changed mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Changed publications to: 32808377, 36553623, 31053103, 27259050, 28202457; Changed phenotypes to: Ataxia-pancytopenia syndrome, OMIM:159550, ataxia-pancytopenia syndrome, MONDO:0008038; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary neuropathy or pain disorder v6.75 SAMD9L Eleanor Williams commented on gene: SAMD9L
Hereditary neuropathy or pain disorder v6.75 ETFDH Sarah Leigh Tag Q3_24_promote_green tag was added to gene: ETFDH.
Tag Q3_24_NHS_review tag was added to gene: ETFDH.
Hereditary neuropathy or pain disorder v6.75 ETFDH Sarah Leigh reviewed gene: ETFDH: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.75 ETFDH Sarah Leigh Publications for gene: ETFDH were set to 32608139; 26821934; 0587156
Hereditary neuropathy or pain disorder v6.74 ETFDH Sarah Leigh Phenotypes for gene: ETFDH were changed from Glutaric acidemia IIC, 231680; Neonatal and late onset forms. hypoglycaemia, metabolic acidosis, and hepatomegaly often preceded by metabolic stress. Muscle involvement in the form of pain, weakness, and lipid storage myopathy also occur. Riboflavin responsive to Glutaric acidemia IIC, OMIM:231680; multiple acyl-CoA dehydrogenase deficiency, MONDO:0009282
Hereditary neuropathy or pain disorder v6.73 ETFDH Sarah Leigh Publications for gene: ETFDH were set to
Hereditary neuropathy or pain disorder v6.72 ERCC8 Sarah Leigh Publications for gene: ERCC8 were set to 7664335; 9338586; 21108394; 14661080; 15744458; 25453614
Hereditary neuropathy or pain disorder v6.71 ERCC8 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: ERCC8.
Tag Q3_24_NHS_review tag was added to gene: ERCC8.
Hereditary neuropathy or pain disorder v6.71 ERCC8 Sarah Leigh reviewed gene: ERCC8: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary neuropathy or pain disorder v6.71 ERCC8 Sarah Leigh Phenotypes for gene: ERCC8 were changed from Cockayne syndrome, Dwarfism, optic atrophy, mental retardation, cutaneous photosensitivity, pigmentary retinopathy, deafness, neuropathy with slow conduction velocities; Cockayne syndrome, type A, 216400 to Cockayne syndrome, type A, OMIM:216400; Cockayne syndrome type 1, MONDO:0019569
Hereditary neuropathy or pain disorder v6.70 ERCC8 Sarah Leigh Publications for gene: ERCC8 were set to 25453614
Hereditary neuropathy or pain disorder v6.69 ERCC8 Sarah Leigh Publications for gene: ERCC8 were set to
Hereditary neuropathy or pain disorder v6.68 ERCC6 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: ERCC6.
Tag Q3_24_NHS_review tag was added to gene: ERCC6.
Hereditary neuropathy or pain disorder v6.68 ERCC6 Sarah Leigh reviewed gene: ERCC6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.68 ERCC6 Sarah Leigh Publications for gene: ERCC6 were set to 25453614
Hereditary neuropathy or pain disorder v6.67 ERCC6 Sarah Leigh Publications for gene: ERCC6 were set to
Hereditary neuropathy or pain disorder v6.66 TBCE Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence available (four unrelated cases) for the promotion of this gene to green rating in the next GMS update.; to: Comment on list classification: There is sufficient evidence available (four unrelated cases) for the association of this gene with neuropathy. Hence, this gene can be promoted to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v6.66 TBCE Achchuthan Shanmugasundram changed review comment from: PMID:27666369 reported six individuals from four apparently unrelated families originating from the same geographical area in Italy near Naples with a similar infantile-onset neurodegenerative disorder. They were either identified with the same homozygous p.Ile155Asn variant (five patients from three families) or with a compound heterozygous variant involving the same variant with another variant (p.Leu360Ter) in one patient. There is also functional evidence available.

This gene has been associated with relevant phenotypes in OMIM (MIM #617207) and Gene2Phenotype (with 'strong' rating on the DD panel). MIM #617207 records axonal peripheral neuropathy as one of the clinical manifestations.; to: PMID:27666369 reported six individuals from four apparently unrelated families originating from the same geographical area in Italy near Naples with a similar infantile-onset neurodegenerative disorder. They were either identified with the same homozygous p.Ile155Asn variant (five patients from three families) or with a compound heterozygous variant involving the same variant with another variant (p.Leu360Ter) in one patient. Electrophysiologic and electromyographic studies in all patients were consistent with a motor neuropathy. There is also functional evidence available.

This gene has been associated with relevant phenotypes in OMIM (MIM #617207) and Gene2Phenotype (with 'strong' rating on the DD panel). MIM #617207 records axonal peripheral neuropathy as one of the clinical manifestations.
Hereditary neuropathy or pain disorder v6.66 ERCC6 Sarah Leigh Phenotypes for gene: ERCC6 were changed from Cockayne syndrome, Dwarfism, optic atrophy, mental retardation, cutaneous photosensitivity, pigmentary retinopathy, deafness, neuropathy with slow conduction velocities; Cockayne syndrome, type B, 133540 to Cockayne syndrome, type B, OMIM:133540; Cockayne syndrome type 2, MONDO:0019570
Intellectual disability v8.6 PI4K2A Tracy Lester gene: PI4K2A was added
gene: PI4K2A was added to Intellectual disability. Sources: NHS GMS
Mode of inheritance for gene: PI4K2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PI4K2A were set to 30564627; 35880319; 32418222
Phenotypes for gene: PI4K2A were set to Intellectual disability; developmental delay; seizures
Penetrance for gene: PI4K2A were set to unknown
Review for gene: PI4K2A was set to GREEN
Added comment: At least three cases have been reported with biallelic variants in this gene and a neurodevelopmental disorder
35880319 - Two patients with PI4K2A deficiency (homozygous variants) were identified by exome sequencing, presenting with developmental and epileptic-dyskinetic encephalopathy. Neuroimaging showed corpus callosum dysgenesis, diffuse white matter volume loss, and hypoplastic vermis. In addition to NDD, we observed recurrent infections and death at toddler age.
30564627 - We report a family of Saudi Arabian ancestry with two children presenting with global developmental delay, dystonia, disturbed sleep, and heat intolerance. By genome sequencing, we identified a nonsense variant in the first exon of PI4K2A that was homozygous in both affected individuals and was absent from, or heterozygous in, seven unaffected siblings.
32418222 - a homozygous missense variant of uncertain significance was suggested to be responsible for some features in a case with NDD and metabolic cutis laxa.
Sources: NHS GMS
Hereditary neuropathy or pain disorder v6.65 TBCE Achchuthan Shanmugasundram Classified gene: TBCE as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.65 TBCE Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (four unrelated cases) for the promotion of this gene to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v6.65 TBCE Achchuthan Shanmugasundram Gene: tbce has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.64 TBCE Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: TBCE.
Tag Q3_24_NHS_review tag was added to gene: TBCE.
Hereditary neuropathy or pain disorder v6.64 TBCE Achchuthan Shanmugasundram reviewed gene: TBCE: Rating: GREEN; Mode of pathogenicity: None; Publications: 27666369; Phenotypes: Encephalopathy, progressive, with amyotrophy and optic atrophy, OMIM:617207; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.64 PNPT1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There are three unrelated cases reported with heterozygous PNPT1 variants and sensory neuropathy. Hence, this gene can be promoted to green rating in the next GMS update.; to: Comment on list classification: There are four unrelated cases reported with heterozygous PNPT1 variants and sensory neuropathy. Hence, this gene can be promoted to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v6.64 PNPT1 Achchuthan Shanmugasundram changed review comment from: PMID:14705117 reported a large family from Southeastern France with spinocerebellar ataxia with sensory involvement. Age at onset ranged from 17 months to 39 years, although most of those affected had onset in childhood. Cerebellar ataxia was always present and many patients had peripheral sensory neuropathy.

PMID:35411967 reported the identification of heterozygous splice site variants in PNPT1 in the above reported family from Southeastern France and from a 3-generation Australian family with spinocerebellar ataxia and sensory neuropathy reported in this study. All patients from the Australian family for whom information was available had an axonal sensory neuropathy with diminished or absent limb reflexes and decreased sensation. A 40-year-old French patient was also reported with heterozygous frameshift PNPT1 variant, who had onset of deafness shortly after birth and onset of gait ataxia at 23 years of age. He also had sensory neuropathy.

This gene has been associated with relevant phenotypes in OMIM (MIM #608703), which records sensory neuropathy/ axonal sensory neuropathy as clinical manifestations of the phenotype.; to: PMID:14705117 reported a large family from Southeastern France with spinocerebellar ataxia with sensory involvement. Age at onset ranged from 17 months to 39 years, although most of those affected had onset in childhood. Cerebellar ataxia was always present and many patients had peripheral sensory neuropathy.

PMID:35411967 reported the identification of heterozygous splice site variants in PNPT1 in the above reported family from Southeastern France and from a 3-generation Australian family with spinocerebellar ataxia and sensory neuropathy reported in this study. All patients from the Australian family for whom information was available had an axonal sensory neuropathy with diminished or absent limb reflexes and decreased sensation. There was evidence of incomplete penetrance in the Australian family, as two carriers in this family had sensory neuropathy without ataxia or cerebellar atrophy in their thirties. A 40-year-old French patient was also reported with heterozygous frameshift PNPT1 variant, who had onset of deafness shortly after birth and onset of gait ataxia at 23 years of age. He also had sensory neuropathy. This patient inherited the variant from an asymptomatic 80+ years old father.

PMID:37935417 reported the identification of a novel PNPT1 variant in a 3-year-old child with spinocerebellar ataxia. The child had cerebellar atrophy and psychomotor delay. At a follow up at 6 years of age, the symptoms had worsened and also presented with axonal sensory neuropathy.

Monoallelic variants in this gene have been associated with relevant phenotype in OMIM (MIM #608703), which records sensory neuropathy/ axonal sensory neuropathy as clinical manifestations of the phenotype.
Hereditary neuropathy or pain disorder v6.64 DSTYK Sarah Leigh Added comment: Comment on phenotypes: Monoallelic DSTYK variants are associated with Congenital anomalies of kidney and urinary tract 1 (OMIM:610805).
Hereditary neuropathy or pain disorder v6.64 DSTYK Sarah Leigh Phenotypes for gene: DSTYK were changed from Spastic paraplegia 23, autosomal recessive, OMIM:270750; hereditary spastic paraplegia 23, MONDO:0010046 to Spastic paraplegia 23, autosomal recessive, OMIM:270750; hereditary spastic paraplegia 23, MONDO:0010046
Hereditary neuropathy or pain disorder v6.63 DSTYK Sarah Leigh Tag founder-effect tag was added to gene: DSTYK.
Hereditary neuropathy or pain disorder v6.63 PNPT1 Achchuthan Shanmugasundram edited their review of gene: PNPT1: Changed publications to: 14705117, 35411967, 37935417
Hereditary neuropathy or pain disorder v6.63 DSTYK Sarah Leigh Classified gene: DSTYK as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.63 DSTYK Sarah Leigh Gene: dstyk has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.62 DSTYK Sarah Leigh edited their review of gene: DSTYK: Added comment: Two DSTYK variants (as compound heterozygotes) have been associated with Spastic paraplegia 23, autosomal recessive (OMIM:270750) in 3 unrelated families of Middle Eastern origin. This combination of variants in the reported families was revealed to be founder effect by haplotype analysis (PMID: 28157540).; Changed rating: AMBER; Changed publications to: 28157540; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Ataxia and cerebellar anomalies - narrow panel v7.3 PNPT1 Achchuthan Shanmugasundram Classified gene: PNPT1 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v7.3 PNPT1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are four unrelated cases with spinocerebellar ataxia 25 (MIM # 608703), although there is evidence of incomplete penetrance in one of them. There is also functional studies available in support of the association. Hence, this gene can be promoted to green rating in the next GMS update.
Ataxia and cerebellar anomalies - narrow panel v7.3 PNPT1 Achchuthan Shanmugasundram Gene: pnpt1 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v7.2 PNPT1 Achchuthan Shanmugasundram gene: PNPT1 was added
gene: PNPT1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Q3_24_promote_green tags were added to gene: PNPT1.
Mode of inheritance for gene: PNPT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PNPT1 were set to 14705117; 35411967; 37935417
Phenotypes for gene: PNPT1 were set to Spinocerebellar ataxia 25, OMIM:608703
Review for gene: PNPT1 was set to GREEN
Added comment: PMID:14705117 reported a large family from Southeastern France with spinocerebellar ataxia with sensory involvement. Age at onset ranged from 17 months to 39 years, although most of those affected had onset in childhood. Cerebellar ataxia was always present and many patients had peripheral sensory neuropathy.

PMID:35411967 reported the identification of heterozygous splice site variants in PNPT1 in the above reported family from Southeastern France and from a 3-generation Australian family with spinocerebellar ataxia and sensory neuropathy reported in this study. There was evidence of incomplete penetrance in the Australian family, as two carriers in this family had sensory neuropathy without ataxia or cerebellar atrophy in their thirties. A 40-year-old French patient was also reported with heterozygous frameshift PNPT1 variant, who had onset of deafness shortly after birth and onset of gait ataxia at 23 years of age. This patient inherited the variant from an asymptomatic 80+ years old father.

PMID:37935417 reported the identification of a novel PNPT1 variant in a 3-year-old child with spinocerebellar ataxia. The child had cerebellar atrophy and psychomotor delay. At a follow up at 6 years of age, the symptoms had worsened and also presented with axonal sensory neuropathy.

Monoallelic variants in this gene have been associated with relevant phenotypes in OMIM (MIM #608703), but not in Gene2Phenotype.
Sources: Literature
Hereditary neuropathy or pain disorder v6.62 DSTYK Sarah Leigh Added comment: Comment on phenotypes: Childhood onset spastic paraplegia, prominent skin pigment abnormalities (vitiligo, hyperpigmentation, diffuse lentigines), premature greying of hair, sensory predominant axonal neuropathy (mild).
Hereditary neuropathy or pain disorder v6.62 DSTYK Sarah Leigh Phenotypes for gene: DSTYK were changed from Childhood onset spastic paraplegia, prominent skin pigment abnormalities (vitiligo, hyperpigmentation, diffuse lentigines), premature greying of hair, sensory predominant axonal neuropathy (mild).; Spastic paraplegia 23, 270750 to Spastic paraplegia 23, autosomal recessive, OMIM:270750; hereditary spastic paraplegia 23, MONDO:0010046
Hereditary neuropathy or pain disorder v6.61 DMXL2 Sarah Leigh Added comment: Comment on phenotypes: Three brothers from a single family with Polyendocrine-polyneuropathy syndrome, OMIM:616113;polyendocrine-polyneuropathy syndrome MONDO:0014497, were homozygous for a DMXL2 variant (PMID: 25248098). Segregation between the variants and the condition was also reported in this study.
Hereditary neuropathy or pain disorder v6.61 DMXL2 Sarah Leigh Phenotypes for gene: DMXL2 were changed from ?Polyendocrine-polyneuropathy syndrome, OMIM:616113; polyendocrine-polyneuropathy syndrome MONDO:0014497; Developmental and epileptic encephalopathy 81, OMIM:618663; developmental and epileptic encephalopathy, 81, MONDO:0032858 to Developmental and epileptic encephalopathy 81, OMIM:618663; developmental and epileptic encephalopathy, 81, MONDO:0032858
Hereditary neuropathy or pain disorder v6.60 DMXL2 Sarah Leigh reviewed gene: DMXL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary neuropathy or pain disorder v6.60 PNPT1 Achchuthan Shanmugasundram Classified gene: PNPT1 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.60 PNPT1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are three unrelated cases reported with heterozygous PNPT1 variants and sensory neuropathy. Hence, this gene can be promoted to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v6.60 PNPT1 Achchuthan Shanmugasundram Gene: pnpt1 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.59 PNPT1 Achchuthan Shanmugasundram Phenotypes for gene: PNPT1 were changed from ataxia; peripheral neuropathy to Spinocerebellar ataxia 25, OMIM:608703
Hereditary neuropathy or pain disorder v6.58 PNPT1 Achchuthan Shanmugasundram Publications for gene: PNPT1 were set to 35411967: 14705117
Hereditary neuropathy or pain disorder v6.57 PNPT1 Achchuthan Shanmugasundram Mode of inheritance for gene: PNPT1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v6.56 PNPT1 Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: PNPT1.
Tag Q3_24_NHS_review tag was added to gene: PNPT1.
Hereditary neuropathy or pain disorder v6.56 PNPT1 Achchuthan Shanmugasundram reviewed gene: PNPT1: Rating: GREEN; Mode of pathogenicity: None; Publications: 14705117, 35411967; Phenotypes: Spinocerebellar ataxia 25, OMIM:608703; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v6.56 DMXL2 Sarah Leigh Publications for gene: DMXL2 were set to 31688942
Hereditary neuropathy or pain disorder v6.55 NFASC Achchuthan Shanmugasundram Classified gene: NFASC as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.55 NFASC Achchuthan Shanmugasundram Added comment: Comment on list classification: There are at least three unrelated cases with syndromic neuropathy. Hence, this gene can be recommended for promotion to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v6.55 NFASC Achchuthan Shanmugasundram Gene: nfasc has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.54 NFASC Achchuthan Shanmugasundram Phenotypes for gene: NFASC were changed from Developmental delay; peripheral neuropathy to Neurodevelopmental disorder with central and peripheral motor dysfunction, OMIM:618356
Hereditary neuropathy or pain disorder v6.53 NFASC Achchuthan Shanmugasundram Publications for gene: NFASC were set to 30850329: 30124836
Hereditary neuropathy or pain disorder v6.52 NFASC Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: NFASC.
Tag Q3_24_NHS_review tag was added to gene: NFASC.
Hereditary neuropathy or pain disorder v6.52 NFASC Achchuthan Shanmugasundram commented on gene: NFASC: PMID:30850329 reported the identification of a homozygous NFASC variant (p.Val1122Glu) in two siblings from an Italian family. The patients presented with early-onset cerebellar ataxia and demyelinating neuropathy.

PMID:31501903 reported the identification of one frameshift and four different homozygous non-synonymous variants in NFASC gene in ten individuals from six unrelated families. They presented with a neurodevelopmental disorder characterised with a spectrum of central (intellectual disability, developmental delay, motor impairment, speech difficulties) and peripheral (early onset demyelinating neuropathy) neurological involvement. Neuropathy was reported in at least three patients from two different families.

This gene has been associated with relevant phenotype in OMIM (MIM #618356), which lists demyelinating sensorimotor polyneuropathy as one of the clinical manifestations observed in some of the patients.
Hereditary neuropathy or pain disorder v6.52 DMXL2 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: DMXL2.
Tag Q3_24_NHS_review tag was added to gene: DMXL2.
Hereditary neuropathy or pain disorder v6.52 DMXL2 Sarah Leigh Phenotypes for gene: DMXL2 were changed from developmental encephalopathy; deafness; mild peripheral polyneuropathy; dysmorphic features to ?Polyendocrine-polyneuropathy syndrome, OMIM:616113; polyendocrine-polyneuropathy syndrome MONDO:0014497; Developmental and epileptic encephalopathy 81, OMIM:618663; developmental and epileptic encephalopathy, 81, MONDO:0032858
Hereditary neuropathy or pain disorder v6.51 AP1S1 Arina Puzriakova Classified gene: AP1S1 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.51 AP1S1 Arina Puzriakova Added comment: Comment on list classification: Neuropathy in adulthood is a feature of MEDNIK syndrome. >3 unrelated cases have been reported. The scope of this panel has now been expanded to complex forms of neuropathy and therefore this gene can be promoted to Green at the next GMS panel update.
Hereditary neuropathy or pain disorder v6.51 AP1S1 Arina Puzriakova Gene: ap1s1 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.50 DMXL2 Sarah Leigh Classified gene: DMXL2 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.50 DMXL2 Sarah Leigh Gene: dmxl2 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.49 DHH Sarah Leigh Classified gene: DHH as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.49 DHH Sarah Leigh Gene: dhh has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.48 DHH Sarah Leigh Tag Q3_24_promote_green tag was added to gene: DHH.
Tag Q3_24_NHS_review tag was added to gene: DHH.
Hereditary neuropathy or pain disorder v6.48 DHH Sarah Leigh edited their review of gene: DHH: Added comment: DHH variants have been associated with 46XY gonadal dysgenesis with minifascicular neuropathy (OMIM:607080). At least five DHH variants have been associated with in five unrelated cases of OMIM:607080.; Changed rating: GREEN
Hereditary neuropathy or pain disorder v6.48 DHH Sarah Leigh Added comment: Comment on phenotypes: DHH variants are also associated with 46XY sex reversal 7 (OMIM:233420). Neuropathy does not appear to be associated with this condition.
Hereditary neuropathy or pain disorder v6.48 DHH Sarah Leigh Phenotypes for gene: DHH were changed from to 46XY gonadal dysgenesis with minifascicular neuropathy, OMIM:607080; 46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome, MONDO:0011766
Hereditary neuropathy or pain disorder v6.47 AP1S1 Arina Puzriakova Tag Q3_24_promote_green tag was added to gene: AP1S1.
Hereditary neuropathy or pain disorder v6.47 AP1S1 Arina Puzriakova Phenotypes for gene: AP1S1 were changed from MEDNIK syndrome, 609313; Congenital onset, Mental retardation, Enteropathy (severe congenital diarrhoea), Deafness, sensory-motor Neuropathy with intermediate conduction velocities, Ichthyosis, Keratoderma to MEDNIK syndrome, OMIM:609313; Congenital onset, Mental retardation, Enteropathy (severe congenital diarrhoea), Deafness, sensory-motor Neuropathy with intermediate conduction velocities, Ichthyosis, Keratoderma
Hereditary neuropathy or pain disorder v6.46 DHH Sarah Leigh Publications for gene: DHH were set to
Hereditary neuropathy or pain disorder v6.45 DHH Sarah Leigh Mode of inheritance for gene: DHH was changed from to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.44 DARS2 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: DARS2.
Tag Q3_24_NHS_review tag was added to gene: DARS2.
Hereditary neuropathy or pain disorder v6.44 DARS2 Sarah Leigh edited their review of gene: DARS2: Added comment: DARS2 variants have been associated with Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, OMIM:611105 and as strong G2P gene for the same condition. At numerous DARS2 variants have been reported in cases of OMIM:611105 (PMID: 28334938;38790244;22677571;38549004).; Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.44 DARS2 Sarah Leigh Publications for gene: DARS2 were set to 28334938
Hereditary neuropathy or pain disorder v6.43 DARS2 Sarah Leigh Added comment: Comment on phenotypes: Slowly progressive spasticity, ataxia and dorsal column dysfunction, sensory-motor axonal neuropathy, characteristic MRI findings
Hereditary neuropathy or pain disorder v6.43 DARS2 Sarah Leigh Phenotypes for gene: DARS2 were changed from Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, 611105; Slowly progressive spasticity, ataxia and dorsal column dysfunction, sensory-motor axonal neuropathy, characteristic MRI findings to Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, OMIM:611105; leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome MONDO:0012622
Hereditary neuropathy or pain disorder v6.42 CYP2U1 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: CYP2U1.
Tag Q3_24_NHS_review tag was added to gene: CYP2U1.
Hereditary neuropathy or pain disorder v6.42 CYP2U1 Sarah Leigh reviewed gene: CYP2U1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.42 CYP2U1 Sarah Leigh Publications for gene: CYP2U1 were set to 23176821; 33107650
Hereditary neuropathy or pain disorder v6.41 CYP2U1 Sarah Leigh Phenotypes for gene: CYP2U1 were changed from spastic paraplegia; cognitive impairment; subvlincial peripheral neuropathy to Spastic paraplegia 56, autosomal recessive, OMIM:615030; hereditary spastic paraplegia 56, MONDO:0014015
Hereditary neuropathy or pain disorder v6.40 CYP2U1 Sarah Leigh Publications for gene: CYP2U1 were set to 23176821
Early onset or syndromic epilepsy v7.1 SLC13A3 Cassandra Smith gene: SLC13A3 was added
gene: SLC13A3 was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: SLC13A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC13A3 were set to 38235040; 34966709; 30635937
Review for gene: SLC13A3 was set to GREEN
Added comment: Febrile seizures reported in >3 families with biallelic variants in SLC13A3
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v7.4 TET2 Arina Puzriakova Tag Q3_24_promote_green tag was added to gene: TET2.
Tag Q3_24_NHS_review tag was added to gene: TET2.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.4 TET2 Arina Puzriakova Classified gene: TET2 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v7.4 TET2 Arina Puzriakova Added comment: Comment on list classification: Total of at least 4 unrelated cases reported to date with an immune dysregulation syndrome and lymphoproliferation (PMIDs: 32518946; 36066697). Sufficient to promote this gene to green with biallelic MOI (3 cases) but not monoallelic (1 case) - possible that in trans variant was missed or the heterozygous variant in LRBA additionally detected in this individual acted as a phenotype-modifier.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.4 TET2 Arina Puzriakova Gene: tet2 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.39 CYP2U1 Sarah Leigh Classified gene: CYP2U1 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.39 CYP2U1 Sarah Leigh Gene: cyp2u1 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.38 CTDP1 Sarah Leigh Phenotypes for gene: CTDP1 were changed from Congenital cataract, facial dysmorphism and demyelinating neuropathy (CCFDN) to Congenital cataracts, facial dysmorphism, and neuropathy, OMIM:604168; congenital cataracts-facial dysmorphism-neuropathy syndrome, MONDO:0011402
Hereditary neuropathy or pain disorder v6.37 NFASC Achchuthan Shanmugasundram reviewed gene: NFASC: Rating: GREEN; Mode of pathogenicity: None; Publications: 30850329, 31501903; Phenotypes: Neurodevelopmental disorder with central and peripheral motor dysfunction, OMIM:618356; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.37 COA7 Sarah Leigh Phenotypes for gene: COA7 were changed from Cerebellar atrophy, leukoencephalopathy and spinal cord atrophy in some patients. Axonal sensory and motor neuropathy; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3, 618387 to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 OMIM:618387; spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 MONDO:0020770
Hereditary neuropathy or pain disorder v6.36 CNTNAP1 Sarah Leigh Phenotypes for gene: CNTNAP1 were changed from Hypomyelinating neuropathy, congenital, 3, 618186 to neuropathy, congenital hypomyelinating, 3, MONDO:0020766; Hypomyelinating neuropathy, congenital, 3, OMIM:618186
Hereditary neuropathy or pain disorder v6.35 CLP1 Sarah Leigh Phenotypes for gene: CLP1 were changed from pontocerbeelar hypoplasia, peripheral neuropathy to Pontocerebellar hypoplasia 10 OMIM:615803; Pontocerebellar hypoplasia type 10 MONDO:0014349
Hereditary neuropathy or pain disorder v6.34 CD59 Sarah Leigh Phenotypes for gene: CD59 were changed from Onset 1st and 2nd decade. Haemolytic anaemia, strokes and relapsing immune-mediated demyelinating neuropathy; Hemolytic anemia, CD59-mediated, with or without immune-mediated polyneuropathy, 612300 to Hemolytic anemia, CD59-mediated, with or without immune-mediated polyneuropathy, OMIM:612300; primary CD59 deficiency, MONDO:0012858
Hereditary neuropathy or pain disorder v6.33 CAPN1 Sarah Leigh Phenotypes for gene: CAPN1 were changed from spasticity; pes cavus; peripheral neuropathy to autosomal recessive spastic paraplegia type 76, MONDO:0014827; Spastic paraplegia 76, autosomal recessive, OMIM:616907
Hereditary neuropathy or pain disorder v6.32 ATP13A2 Sarah Leigh Phenotypes for gene: ATP13A2 were changed from spastic paraplegia; cognitive impairment; peripheral neuropathy to Spastic paraplegia 78, autosomal recessive, OMIM:617225; Kufor-Rakeb syndrome, OMIM:606693; Kufor-Rakeb syndrome, MONDO:0011706; autosomal recessive spastic paraplegia type 78, MONDO:0014975
Hereditary neuropathy or pain disorder v6.31 ATM Sarah Leigh Phenotypes for gene: ATM were changed from Ataxia-telangiectasia, OMIM:208900; Hereditary Neuropathies to Ataxia-telangiectasia, OMIM:208900
Hereditary neuropathy or pain disorder v6.30 ATL3 Sarah Leigh Phenotypes for gene: ATL3 were changed from to Neuropathy, hereditary sensory, type IF, OMIM:615632; neuropathy, hereditary sensory, type 1F, MONDO:0014286
Hereditary neuropathy or pain disorder v6.29 ATAD3A Sarah Leigh Phenotypes for gene: ATAD3A were changed from global developmental delay; hypotonia; optic atrophy; axonal neuropathy; hypertrophic cardiomyopathy to Harel-Yoon syndrome, OMIM:617183; Harel-Yoon syndrome, MONDO:0014958
Primary immunodeficiency or monogenic inflammatory bowel disease v7.3 TET2 Arina Puzriakova Publications for gene: TET2 were set to 32518946
Hereditary neuropathy or pain disorder v6.28 ASAH1 Sarah Leigh Phenotypes for gene: ASAH1 were changed from Progressive myoclonic epilepsy; motor neuropathy to spinal muscular atrophy-progressive myoclonic epilepsy syndrome, MONDO:0008045; Spinal muscular atrophy with progressive myoclonic epilepsy, OMIM:159950
Hereditary neuropathy or pain disorder v6.27 ABCD1 Sarah Leigh Phenotypes for gene: ABCD1 were changed from adreno leukodystrophy; adrenomyeloneuropathy to Adrenoleukodystrophy, OMIM:300100; Adrenomyeloneuropathy, adult, OMIM:300100; adrenoleukodystrophy, MONDO:0018544
Hereditary neuropathy or pain disorder v6.26 AP5Z1 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: AP5Z1.
Tag Q3_24_NHS_review tag was added to gene: AP5Z1.
Primary immunodeficiency or monogenic inflammatory bowel disease v7.2 TET2 Arina Puzriakova Added comment: Comment on phenotypes: This gene is now associated with a relevant phenotype in OMIM (Immunodeficiency 75, OMIM:619126)
Primary immunodeficiency or monogenic inflammatory bowel disease v7.2 TET2 Arina Puzriakova Phenotypes for gene: TET2 were changed from Primary Immunodeficiency; Lymphoma; Hepatosplenomegaly; Autoimmunity; Developmental delay to Immunodeficiency 75, OMIM:619126
Hereditary neuropathy or pain disorder v6.26 ARL6IP1 Sarah Leigh Classified gene: ARL6IP1 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.26 ARL6IP1 Sarah Leigh Gene: arl6ip1 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.25 ARL6IP1 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: ARL6IP1.
Tag Q3_24_NHS_review tag was added to gene: ARL6IP1.
Hereditary neuropathy or pain disorder v6.25 ASAH1 Sarah Leigh Classified gene: ASAH1 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.25 ASAH1 Sarah Leigh Gene: asah1 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.24 ASAH1 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: ASAH1.
Tag Q3_24_NHS_review tag was added to gene: ASAH1.
Hereditary neuropathy or pain disorder v6.24 ATAD3A Sarah Leigh Tag Q3_24_promote_green tag was added to gene: ATAD3A.
Tag Q3_24_NHS_review tag was added to gene: ATAD3A.
Hereditary neuropathy or pain disorder v6.24 ATAD3A Sarah Leigh Classified gene: ATAD3A as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.24 ATAD3A Sarah Leigh Gene: atad3a has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.23 ATM Sarah Leigh Tag Q3_24_promote_green tag was added to gene: ATM.
Tag Q3_24_NHS_review tag was added to gene: ATM.
Hereditary neuropathy or pain disorder v6.23 ATL3 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: ATL3.
Tag Q3_24_NHS_review tag was added to gene: ATL3.
Hereditary neuropathy or pain disorder v6.23 ATP13A2 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: ATP13A2.
Tag Q3_24_NHS_review tag was added to gene: ATP13A2.
Hereditary neuropathy or pain disorder v6.23 ATP13A2 Sarah Leigh Classified gene: ATP13A2 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.23 ATP13A2 Sarah Leigh Gene: atp13a2 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.22 BAG3 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: BAG3.
Tag Q3_24_NHS_review tag was added to gene: BAG3.
Hereditary neuropathy or pain disorder v6.22 C12orf65 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: C12orf65.
Tag Q3_24_NHS_review tag was added to gene: C12orf65.
Hereditary neuropathy or pain disorder v6.22 CAPN1 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: CAPN1.
Tag Q3_24_NHS_review tag was added to gene: CAPN1.
Hereditary neuropathy or pain disorder v6.22 CAPN1 Sarah Leigh Classified gene: CAPN1 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.22 CAPN1 Sarah Leigh Gene: capn1 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.21 CLP1 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: CLP1.
Tag Q3_24_NHS_review tag was added to gene: CLP1.
Hereditary neuropathy or pain disorder v6.21 CLP1 Sarah Leigh Classified gene: CLP1 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.21 CLP1 Sarah Leigh Gene: clp1 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.20 CD59 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: CD59.
Tag Q3_24_NHS_review tag was added to gene: CD59.
Hereditary neuropathy or pain disorder v6.20 CNTNAP1 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: CNTNAP1.
Tag Q3_24_NHS_review tag was added to gene: CNTNAP1.
Hereditary neuropathy or pain disorder v6.20 COA7 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: COA7.
Tag Q3_24_NHS_review tag was added to gene: COA7.
Hereditary neuropathy or pain disorder v6.20 CTDP1 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: CTDP1.
Tag Q3_24_NHS_review tag was added to gene: CTDP1.
Hereditary neuropathy or pain disorder v6.20 CTDP1 Sarah Leigh reviewed gene: CTDP1: Rating: GREEN; Mode of pathogenicity: ; Publications: 15322984, 20301787, 10439962, 29174527, 14517542, 16194727, 24690360, 21824574, 23408394; Phenotypes: Congenital cataracts, facial dysmorphism, and neuropathy, OMIM:604168, congenital cataracts-facial dysmorphism-neuropathy syndrome, MONDO:0011402; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.20 COA7 Sarah Leigh reviewed gene: COA7: Rating: GREEN; Mode of pathogenicity: ; Publications: 29718187, 27683825; Phenotypes: Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 OMIM:618387, spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3 MONDO:0020770; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.20 CNTNAP1 Sarah Leigh reviewed gene: CNTNAP1: Rating: GREEN; Mode of pathogenicity: ; Publications: 27668699, 28374019, 27818385, 27782105, 29511323; Phenotypes: neuropathy, congenital hypomyelinating, 3, MONDO:0020766, Hypomyelinating neuropathy, congenital, 3, OMIM:618186; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.20 CD59 Sarah Leigh reviewed gene: CD59: Rating: GREEN; Mode of pathogenicity: ; Publications: 23149847, 1382994, 24382084; Phenotypes: Hemolytic anemia, CD59-mediated, with or without immune-mediated polyneuropathy, OMIM:612300, primary CD59 deficiency, MONDO:0012858; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.20 CLP1 Sarah Leigh reviewed gene: CLP1: Rating: GREEN; Mode of pathogenicity: ; Publications: 24766810, 23474986, 24766809, 29307788; Phenotypes: Pontocerebellar hypoplasia 10 OMIM:615803, Pontocerebellar hypoplasia type 10 MONDO:0014349; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.20 CAPN1 Sarah Leigh reviewed gene: CAPN1: Rating: GREEN; Mode of pathogenicity: ; Publications: 23741357, 27153400; Phenotypes: autosomal recessive spastic paraplegia type 76, MONDO:0014827, Spastic paraplegia 76, autosomal recessive, OMIM:616907; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.20 C12orf65 Sarah Leigh reviewed gene: C12orf65: Rating: GREEN; Mode of pathogenicity: ; Publications: 24198383, 23188110, 24424123, 24080142; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.20 BAG3 Sarah Leigh reviewed gene: BAG3: Rating: GREEN; Mode of pathogenicity: ; Publications: 37989284, 30145633, 37907725, 25208129; Phenotypes: Myopathy, myofibrillar, 6, OMIM:612954, myofibrillar myopathy 6, MONDO:0013061, dilated cardiomyopathy 1HH, MONDO:0013479, Cardiomyopathy, dilated, 1HH, OMIM:613881; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Hereditary neuropathy or pain disorder v6.20 ATP13A2 Sarah Leigh reviewed gene: ATP13A2: Rating: GREEN; Mode of pathogenicity: ; Publications: 28137957, 27217339, 22296644; Phenotypes: Spastic paraplegia 78, autosomal recessive, OMIM:617225, Kufor-Rakeb syndrome, OMIM:606693, Kufor-Rakeb syndrome, MONDO:0011706, autosomal recessive spastic paraplegia type 78, MONDO:0014975; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.20 ATL3 Sarah Leigh reviewed gene: ATL3: Rating: GREEN; Mode of pathogenicity: ; Publications: 24736309, 24459106, 30680846; Phenotypes: Neuropathy, hereditary sensory, type IF, OMIM:615632, neuropathy, hereditary sensory, type 1F, MONDO:0014286; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v6.20 ATM Sarah Leigh reviewed gene: ATM: Rating: GREEN; Mode of pathogenicity: ; Publications: 37540892; Phenotypes: Ataxia-telangiectasia, OMIM:208900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.20 ATAD3A Sarah Leigh reviewed gene: ATAD3A: Rating: GREEN; Mode of pathogenicity: ; Publications: 27640307; Phenotypes: Harel-Yoon syndrome, OMIM:617183, Harel-Yoon syndrome, MONDO:0014958; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.20 ASAH1 Sarah Leigh reviewed gene: ASAH1: Rating: GREEN; Mode of pathogenicity: ; Publications: 534421, 22703880; Phenotypes: spinal muscular atrophy-progressive myoclonic epilepsy syndrome, MONDO:0008045, Spinal muscular atrophy with progressive myoclonic epilepsy, OMIM:159950; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.20 ARL6IP1 Sarah Leigh reviewed gene: ARL6IP1: Rating: GREEN; Mode of pathogenicity: ; Publications: 28471035, 31272422, 33188530, 30237576, 24482476, 30980493; Phenotypes: Spastic paraplegia 61, autosomal recessive, OMIM:615685, hereditary spastic paraplegia 61, MONDO:0014304; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.20 AP5Z1 Sarah Leigh reviewed gene: AP5Z1: Rating: GREEN; Mode of pathogenicity: ; Publications: 20613862: 24833714; Phenotypes: Spastic paraplegia 48, autosomal recessive, OMIM:613647; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cystic kidney disease v7.4 COL4A3 Arina Puzriakova Tag watchlist tag was added to gene: COL4A3.
Cystic kidney disease v7.4 COL4A3 Arina Puzriakova Classified gene: COL4A3 as Amber List (moderate evidence)
Cystic kidney disease v7.4 COL4A3 Arina Puzriakova Added comment: Comment on list classification: There is some evidence that shows some patients with COL4A3-related Alport syndrome have multicystic kidney disease (MKD).

PMID: 38178635 - Bada-Bosch et al 2024 - at least 8 unrelated individuals with heterozygous LP/P variants in the COL4A3 and MKD.

However, a substantial proportion of AD Alport Syndrome patients maintain normal kidney function throughout life and the factors underlying the development of kidney disease remain incompletely understood.

Rating Amber given that inclusion of other Alport genes COL4A4/5 on this panel was rejected on GMS expert review but monitoring of this association should be continued (added watchlist tag).
Cystic kidney disease v7.4 COL4A3 Arina Puzriakova Gene: col4a3 has been classified as Amber List (Moderate Evidence).
Cystic kidney disease v7.3 COL4A5 Arina Puzriakova Publications for gene: COL4A5 were set to 31922066
Cystic kidney disease v7.2 COL4A4 Arina Puzriakova Publications for gene: COL4A4 were set to 31922066
Cystic kidney disease v7.1 CYP24A1 John Sayer gene: CYP24A1 was added
gene: CYP24A1 was added to Cystic kidney disease. Sources: Expert list
Mode of inheritance for gene: CYP24A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CYP24A1 were set to 34307984; 22337913; 27105398; 28324001
Phenotypes for gene: CYP24A1 were set to cystic kidney disease; nephrocalcinosis; hypercalcaemia
Penetrance for gene: CYP24A1 were set to Complete
Review for gene: CYP24A1 was set to GREEN
Added comment: Can give cystic kidney disease (mild, atypical) but useful to be added to R193 panel
Sources: Expert list
Primary immunodeficiency or monogenic inflammatory bowel disease v7.1 IL7 Cassandra Smith gene: IL7 was added
gene: IL7 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Mode of inheritance for gene: IL7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IL7 were set to 39352394
Added comment: 4 families with biallelic LOF variants and immune deficiency. 2 families share the same variant on the same haplotype, still leaving three unrelated families.

Functional study investigates impact on immune system cells.

No biallelic pLOF variants in gnomAD.
Sources: Literature
COVID-19 research v1.142 IL7 Cassandra Smith Deleted their review
COVID-19 research v1.142 IL7 Cassandra Smith Deleted their comment
COVID-19 research v1.142 IL7 Cassandra Smith reviewed gene: IL7: Rating: GREEN; Mode of pathogenicity: None; Publications: 39352394; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v8.6 PLA2G16 Eleanor Williams Tag Q3_24_promote_green was removed from gene: PLA2G16.
Tag Q3_24_NHS_review was removed from gene: PLA2G16.
Intellectual disability v8.6 PLA2G16 Eleanor Williams Classified gene: PLA2G16 as Amber List (moderate evidence)
Intellectual disability v8.6 PLA2G16 Eleanor Williams Added comment: Comment on list classification: Rating as amber. 3 cases with intellectual disability but the severity is not noted.
Intellectual disability v8.6 PLA2G16 Eleanor Williams Gene: pla2g16 has been classified as Amber List (Moderate Evidence).
Intellectual disability v8.5 PLA2G16 Eleanor Williams Deleted their comment
Intellectual disability v8.5 PLA2G16 Eleanor Williams Deleted their comment
Severe insulin resistance and lipodystrophy syndromes v4.60 PLA2G16 Eleanor Williams Tag Q3_24_NHS_review was removed from gene: PLA2G16.
Severe insulin resistance and lipodystrophy syndromes v4.60 PLA2G16 Eleanor Williams Classified gene: PLA2G16 as Amber List (moderate evidence)
Severe insulin resistance and lipodystrophy syndromes v4.60 PLA2G16 Eleanor Williams Added comment: Comment on list classification: Rating as amber but with a recommendation for green rating following GMS review. 4 cases with 3 different variants in PLA2G16/PLAAT3 and a consistent phenotype that includes lipoatrophy and insulin resistance with childhood onset of symptoms.
Severe insulin resistance and lipodystrophy syndromes v4.60 PLA2G16 Eleanor Williams Gene: pla2g16 has been classified as Amber List (Moderate Evidence).
Severe insulin resistance and lipodystrophy syndromes v4.59 PLA2G16 Eleanor Williams Deleted their comment
Severe insulin resistance and lipodystrophy syndromes v4.59 PLA2G16 Eleanor Williams Deleted their comment
Severe insulin resistance and lipodystrophy syndromes v4.59 PLA2G16 Eleanor Williams changed review comment from: Comment on list classification: Promoting to amber with recommendation for green rating following GMS review. 4 cases with 3 different variants in PLAAT3 and a consistent phenotype that includes peripheral neuropathy.; to: Comment on list classification: Promoting to amber with recommendation for green rating following GMS review. 4 cases with 3 different variants in PLAAT3 and a consistent phenotype that includes lipodystrophy and insulin resistance with childhood onset.
Severe insulin resistance and lipodystrophy syndromes v4.59 PLA2G6 Eleanor Williams Phenotypes for gene: PLA2G6 were changed from Associated with Lipodystrophy, familial partial, type 9, OMIM:620683; lipodystrophy, familial partial, type 9, MONDO:0958034 to none
Severe insulin resistance and lipodystrophy syndromes v4.58 PLA2G6 Eleanor Williams Publications for gene: PLA2G6 were set to 37919452
Severe insulin resistance and lipodystrophy syndromes v4.57 PLA2G6 Eleanor Williams Classified gene: PLA2G6 as No list
Severe insulin resistance and lipodystrophy syndromes v4.57 PLA2G6 Eleanor Williams Gene: pla2g6 has been removed from the panel.
Severe insulin resistance and lipodystrophy syndromes v4.56 PLA2G16 Eleanor Williams Entity copied from Hereditary neuropathy or pain disorder v6.19
Severe insulin resistance and lipodystrophy syndromes v4.56 PLA2G16 Eleanor Williams gene: PLA2G16 was added
gene: PLA2G16 was added to Lipodystrophy - childhood onset. Sources: Expert list,Expert Review Amber
new-gene-name, Q3_24_promote_green, Q3_24_NHS_review tags were added to gene: PLA2G16.
Mode of inheritance for gene: PLA2G16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLA2G16 were set to 37919452
Phenotypes for gene: PLA2G16 were set to Associated with Lipodystrophy, familial partial, type 9, OMIM:620683; lipodystrophy, familial partial, type 9, MONDO:0958034
Intellectual disability v8.5 PLA2G16 Eleanor Williams Entity copied from Hereditary neuropathy or pain disorder v6.19
Intellectual disability v8.5 PLA2G16 Eleanor Williams gene: PLA2G16 was added
gene: PLA2G16 was added to Intellectual disability. Sources: Expert list,Expert Review Amber
new-gene-name, Q3_24_promote_green, Q3_24_NHS_review tags were added to gene: PLA2G16.
Mode of inheritance for gene: PLA2G16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLA2G16 were set to 37919452
Phenotypes for gene: PLA2G16 were set to Associated with Lipodystrophy, familial partial, type 9, OMIM:620683; lipodystrophy, familial partial, type 9, MONDO:0958034
Severe insulin resistance and lipodystrophy syndromes v4.55 PLA2G6 Eleanor Williams commented on gene: PLA2G6
Severe insulin resistance and lipodystrophy syndromes v4.55 PLA2G6 Eleanor Williams Deleted their review
Severe insulin resistance and lipodystrophy syndromes v4.55 PLA2G6 Eleanor Williams Deleted their comment
Hereditary neuropathy or pain disorder v6.19 PLA2G16 Eleanor Williams changed review comment from: Associated with Lipodystrophy, familial partial, type 9 620683 (AR) in OMIM where Demyelinating sensorimotor neuropathy is listed as a clinical feature.

PMID: 37919452 - Schuermans et al 2023 - 7 patients from 4 unrelated families with 3 different homozygous variants (c.16-4823_118+167del p.(Pro6ValfsTer15), c.286dupG p.(Ala96GlyfsTer16) and c.339C>A p.(Cys113Ter). All patients had generalized or partial Lipoatrophy, insulin resistance and Liver steatosis, and 6/7 showed Dyslipidemia/hypertriglyceridemia. Demyelinating peripheral neuropathy was seen in 5/7 patients from all 4 families.

Function studies with PLAAT3 inactivation in human adipose stem cells provides evidence for PLAAT3 in PPARγ-mediated adipogenesis.; to: Associated with Lipodystrophy, familial partial, type 9 620683 (AR) in OMIM where Demyelinating sensorimotor neuropathy is listed as a clinical feature.

PMID: 37919452 - Schuermans et al 2023 - 7 patients from 4 unrelated families with 3 different homozygous variants (c.16-4823_118+167del p.(Pro6ValfsTer15), c.286dupG p.(Ala96GlyfsTer16) and c.339C>A p.(Cys113Ter). All patients had generalized or partial lipoatrophy, insulin resistance and Liver steatosis, and 6/7 showed Dyslipidemia/hypertriglyceridemia. Demyelinating peripheral neuropathy was seen in 5/7 patients from all 4 families. Psychomotor retardation/intellectual disability was observed in 3/7 patients but the severity is not recorded.

Age of onset of symptoms was 19 years, 8 years, 9 months, 4 years, 4 years (not available for 2 patients).

Function studies with PLAAT3 inactivation in human adipose stem cells provides evidence for PLAAT3 in PPARγ-mediated adipogenesis.
Severe insulin resistance and lipodystrophy syndromes v4.55 PLA2G6 Eleanor Williams gene: PLA2G6 was added
gene: PLA2G6 was added to Lipodystrophy - childhood onset. Sources: Literature
Mode of inheritance for gene: PLA2G6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLA2G6 were set to 37919452
Phenotypes for gene: PLA2G6 were set to Associated with Lipodystrophy, familial partial, type 9, OMIM:620683; lipodystrophy, familial partial, type 9, MONDO:0958034
Added comment: Associated with Lipodystrophy, familial partial, type 9 620683 (AR) in OMIM where Demyelinating sensorimotor neuropathy is listed as a clinical feature.

PMID: 37919452 - Schuermans et al 2023 - 7 patients from 4 unrelated families with 3 different homozygous variants (c.16-4823_118+167del p.(Pro6ValfsTer15), c.286dupG p.(Ala96GlyfsTer16) and c.339C>A p.(Cys113Ter). All patients had generalized or partial lipoatrophy, insulin resistance and Liver steatosis, and 6/7 showed Dyslipidemia/hypertriglyceridemia. Demyelinating peripheral neuropathy was seen in 5/7 patients from all 4 families. Psychomotor retardation/intellectual disability was observed in 3/7 patients but the severity is not recorded.

Age of onset of symptoms was 19 years, 8 years, 9 months, 4 years, 4 years (not available for 2 patients).

Function studies with PLAAT3 inactivation in human adipose stem cells provides evidence for PLAAT3 in PPARγ-mediated adipogenesis.
Sources: Literature
Hereditary neuropathy or pain disorder v6.19 PLA2G16 Eleanor Williams Classified gene: PLA2G16 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.19 PLA2G16 Eleanor Williams Added comment: Comment on list classification: Promoting to amber with recommendation for green rating following GMS review. 4 cases with 3 different variants in PLAAT3 and a consistent phenotype that includes peripheral neuropathy.
Hereditary neuropathy or pain disorder v6.19 PLA2G16 Eleanor Williams Gene: pla2g16 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.18 PLA2G16 Eleanor Williams Phenotypes for gene: PLA2G16 were changed from to Associated with Lipodystrophy, familial partial, type 9, OMIM:620683; lipodystrophy, familial partial, type 9, MONDO:0958034
Hereditary neuropathy or pain disorder v6.17 PLA2G16 Eleanor Williams Tag new-gene-name tag was added to gene: PLA2G16.
Tag Q3_24_promote_green tag was added to gene: PLA2G16.
Tag Q3_24_NHS_review tag was added to gene: PLA2G16.
Hereditary neuropathy or pain disorder v6.17 PLA2G16 Eleanor Williams commented on gene: PLA2G16: The new gene name for PLA2G16 is PLAAT3.
Hereditary neuropathy or pain disorder v6.17 PLA2G16 Eleanor Williams edited their review of gene: PLA2G16: Added comment: Associated with Lipodystrophy, familial partial, type 9 620683 (AR) in OMIM where Demyelinating sensorimotor neuropathy is listed as a clinical feature.

PMID: 37919452 - Schuermans et al 2023 - 7 patients from 4 unrelated families with 3 different homozygous variants (c.16-4823_118+167del p.(Pro6ValfsTer15), c.286dupG p.(Ala96GlyfsTer16) and c.339C>A p.(Cys113Ter). All patients had generalized or partial Lipoatrophy, insulin resistance and Liver steatosis, and 6/7 showed Dyslipidemia/hypertriglyceridemia. Demyelinating peripheral neuropathy was seen in 5/7 patients from all 4 families.

Function studies with PLAAT3 inactivation in human adipose stem cells provides evidence for PLAAT3 in PPARγ-mediated adipogenesis.; Changed phenotypes to: Associated with Lipodystrophy, familial partial, type 9, OMIM:620683, lipodystrophy, familial partial, type 9, MONDO:0958034
Hereditary neuropathy or pain disorder v6.17 PLA2G16 Eleanor Williams gene: PLA2G16 was added
gene: PLA2G16 was added to Hereditary neuropathy or pain disorder. Sources: Expert list
Mode of inheritance for gene: PLA2G16 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLA2G16 were set to 37919452
Added comment: Added as green by Alexander Rossor (UCL Institute of Neurology) - see https://panelapp.genomicsengland.co.uk/panels/846/gene/PLAA/
Sources: Expert list
Hereditary neuropathy or pain disorder v6.16 PLAA Eleanor Williams changed review comment from: The paper PMID:37919452 refers to gene PLAAT3, PLA2G16 and mentions transcript NM_001128203. This corresponds to the gene PLA2G16 with Ensembl ID ENSG00000176485 in the current PanelApp database and not PLAA ENSG00000137055.

Therefore this review will be copied to PLA2G16 and PLAA will have the tag 'curated_removed' added.; to: The paper PMID:37919452 refers to gene PLAAT3 previously known as PLA2G16 and mentions transcript NM_001128203. This corresponds to the gene PLA2G16 with Ensembl ID ENSG00000176485 in the current PanelApp database and not PLAA ENSG00000137055.

Therefore this review will be copied to PLA2G16 and PLAA will have the tag 'curated_removed' added.
Hereditary neuropathy or pain disorder v6.16 PLAA Eleanor Williams changed review comment from: The paper PMID:37919452 refers to gene PLAAT3, PLA2G16 and mentions transcript NM_001128203. This corresponds to the gene PLA2G16 with Ensembl ID ENSG00000176485 in the current PanelApp database and not PLAA ENSG00000137055.

Therefore this review will be copied to PLA2G16 and PLAA will have the tag 'curator_removed' added.; to: The paper PMID:37919452 refers to gene PLAAT3, PLA2G16 and mentions transcript NM_001128203. This corresponds to the gene PLA2G16 with Ensembl ID ENSG00000176485 in the current PanelApp database and not PLAA ENSG00000137055.

Therefore this review will be copied to PLA2G16 and PLAA will have the tag 'curated_removed' added.
Hereditary neuropathy or pain disorder v6.16 PLAA Eleanor Williams Tag curated_removed tag was added to gene: PLAA.
Hereditary neuropathy or pain disorder v6.16 PLAA Eleanor Williams commented on gene: PLAA
Hereditary neuropathy or pain disorder v6.16 NDUFS6 Eleanor Williams Publications for gene: NDUFS6 were set to 38459834; 38549004
Hereditary neuropathy or pain disorder v6.15 NDUFS6 Eleanor Williams Tag Q3_24_promote_green tag was added to gene: NDUFS6.
Tag Q3_24_NHS_review tag was added to gene: NDUFS6.
Hereditary neuropathy or pain disorder v6.15 NDUFS6 Eleanor Williams Classified gene: NDUFS6 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.15 NDUFS6 Eleanor Williams Added comment: Comment on list classification: Promoting to amber with a recommendation for green rating following GMS review. 3 separate publications report variants in this gene in patients with peripheral neuropathies. 2 different variants are reported.
Hereditary neuropathy or pain disorder v6.15 NDUFS6 Eleanor Williams Gene: ndufs6 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.14 NDUFS6 Eleanor Williams changed review comment from: Associated with Mitochondrial complex I deficiency, nuclear type 9, OMIM: 618232 (AR)

Biallelic loss of function variants are associated with severe CI deficiency and Leigh syndrome in previous reports (PubMed: 19259137 and PubMed: 15372108).

There is now phenotypic expansion with 4 families reported with a less severe phenotype. 3 families share a common variant.

PMID: 38459834 - Camila Armirola-Ricaurte et al 2024. Describe 5 patients from 3 unrelated families from Spain, Turkey and Greece. They share a homozygous NDUFS6 NM_004553.6:c.309+5G>A variant found be exome sequencing and an axonal Charcot-Marie-Tooth (CMT) neuropathy. Age of onset ranged from 1 to 10 years. In all cases the unaffected parents were heterozygous for the variant. The variant is predicted to affect splicing and in family 1 was shown to cause the expression of aberrantly spliced transcripts and negligible levels of the canonical transcript. Haplotype analysis showed that the variant lies on a shared haplotype of 0.74MB on chromosome 5 and estimate the most recent common ancestor with the haplotype would have lived 740 years ago

PMID: 38549004 – Ferreira et al 2024 – screened nearly 11,000 patients with peripheral neuropathy for variants in known mitochondrial disease genes. 1 male was found with a homozygous variant c.320_323delCAAA, p.Thr107LysfsTer40 in NDUFS6.; to: Associated with Mitochondrial complex I deficiency, nuclear type 9, OMIM: 618232 (AR)

Biallelic loss of function variants are associated with severe CI deficiency and Leigh syndrome in previous reports (PubMed: 19259137 Spiegal et al 2009 and PubMed: 15372108 Kirby et al 2004, PMID: 30948790 - Rouzier et al 2019, PMID: 22474353 Ke et al 2012).

There is now phenotypic expansion with 5 families reported with a less severe phenotype. 4 families share a common variant.

PMID: 38459834 - Armirola-Ricaurte et al 2024. Describe 5 patients from 3 unrelated families from Spain, Turkey and Greece. They share a homozygous NDUFS6 NM_004553.6:c.309+5G>A variant found be exome sequencing and an axonal Charcot-Marie-Tooth (CMT) neuropathy. Age of onset ranged from 1 to 10 years. In all cases the unaffected parents were heterozygous for the variant. The variant is predicted to affect splicing and in family 1 was shown to cause the expression of aberrantly spliced transcripts and negligible levels of the canonical transcript. Haplotype analysis showed that the variant lies on a shared haplotype of 0.74MB on chromosome 5 and estimate the most recent common ancestor with the haplotype would have lived 740 years ago

PMID: 38549004 – Ferreira et al 2024 – screened nearly 11,000 patients with peripheral neuropathy for variants in known mitochondrial disease genes. 1 male was found with a homozygous variant c.320_323delCAAA, p.Thr107LysfsTer40 in NDUFS6.

PMID: 38217609 - Gangfuß et al 2024 - identified a homozygous variant (c.309 + 5 G > A) in NDUFS6 in one male patient aged 10 with axonal neuropathy accompanied by loss of small fibers in skin biopsy. The patient also showed optic atrophy and borderline intellectual disability.
Hereditary neuropathy or pain disorder v6.14 NDUFS6 Eleanor Williams changed review comment from: Associated with Mitochondrial complex I deficiency, nuclear type 9, OMIM: 618232 (AR)

Biallelic loss of function variants are associated with severe CI deficiency and Leigh syndrome. 4 families reported although 3 share a common variant.

PMID: 38459834 - Camila Armirola-Ricaurte et al 2024. Describe 5 patients from 3 unrelated families from Spain, Turkey and Greece. They share a homozygous NDUFS6 NM_004553.6:c.309+5G>A variant found be exome sequencing and an axonal Charcot-Marie-Tooth (CMT) neuropathy. Age of onset ranged from 1 to 10 years. In all cases the unaffected parents were heterozygous for the variant. The variant is predicted to affect splicing and in family 1 was shown to cause the expression of aberrantly spliced transcripts and negligible levels of the canonical transcript. Haplotype analysis showed that the variant lies on a shared haplotype of 0.74MB on chromosome 5 and estimate the most recent common ancestor with the haplotype would have lived 740 years ago

PMID: 38549004 – Ferreira et al 2024 – screened nearly 11,000 patients with peripheral neuropathy for variants in known mitochondrial disease genes. 1 male was found with a homozygous variant c.320_323delCAAA, p.Thr107LysfsTer40 in NDUFS6.; to: Associated with Mitochondrial complex I deficiency, nuclear type 9, OMIM: 618232 (AR)

Biallelic loss of function variants are associated with severe CI deficiency and Leigh syndrome in previous reports (PubMed: 19259137 and PubMed: 15372108).

There is now phenotypic expansion with 4 families reported with a less severe phenotype. 3 families share a common variant.

PMID: 38459834 - Camila Armirola-Ricaurte et al 2024. Describe 5 patients from 3 unrelated families from Spain, Turkey and Greece. They share a homozygous NDUFS6 NM_004553.6:c.309+5G>A variant found be exome sequencing and an axonal Charcot-Marie-Tooth (CMT) neuropathy. Age of onset ranged from 1 to 10 years. In all cases the unaffected parents were heterozygous for the variant. The variant is predicted to affect splicing and in family 1 was shown to cause the expression of aberrantly spliced transcripts and negligible levels of the canonical transcript. Haplotype analysis showed that the variant lies on a shared haplotype of 0.74MB on chromosome 5 and estimate the most recent common ancestor with the haplotype would have lived 740 years ago

PMID: 38549004 – Ferreira et al 2024 – screened nearly 11,000 patients with peripheral neuropathy for variants in known mitochondrial disease genes. 1 male was found with a homozygous variant c.320_323delCAAA, p.Thr107LysfsTer40 in NDUFS6.
Hereditary neuropathy or pain disorder v6.14 NDUFS6 Eleanor Williams Phenotypes for gene: NDUFS6 were changed from Mitochondrial complex I deficiency, nuclear type 9, OMIM: 618232; mitochondrial complex 1 deficiency, nuclear type 9, MONDO:0032615 to Mitochondrial complex I deficiency, nuclear type 9, OMIM: 618232; mitochondrial complex 1 deficiency, nuclear type 9, MONDO:0032615
Hereditary neuropathy or pain disorder v6.13 NDUFS6 Eleanor Williams Phenotypes for gene: NDUFS6 were changed from peripheral neuropathy; nystagmus to Mitochondrial complex I deficiency, nuclear type 9, OMIM: 618232; mitochondrial complex 1 deficiency, nuclear type 9, MONDO:0032615
Hereditary neuropathy or pain disorder v6.12 NDUFS6 Eleanor Williams Publications for gene: NDUFS6 were set to 38459834 : 38549004
Hereditary neuropathy or pain disorder v6.11 NDUFS6 Eleanor Williams edited their review of gene: NDUFS6: Changed publications to: 38459834, 38549004; Changed phenotypes to: Mitochondrial complex I deficiency, nuclear type 9, OMIM: 618232, mitochondrial complex 1 deficiency, nuclear type 9, MONDO:0032615; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v6.11 NDUFS6 Eleanor Williams commented on gene: NDUFS6
Hereditary neuropathy or pain disorder v6.11 NOP56_GGCCTG Arina Puzriakova Publications for STR: NOP56_GGCCTG were set to
Adult onset neurodegenerative disorder v7.1 NOP56_GGCCTG Arina Puzriakova commented on STR: NOP56_GGCCTG: Heterozygous expansion of an intronic GGCCTG hexanucleotide repeat in the NOP56 gene causes spinocerebellar ataxia-36 (SCA36), an adult-onset slowly progressive neurodegenerative disorder which is within the scope of this panel. Sufficient unrelated cases to support the gene-disease association. Flagging for additional GMS review to determine whether inclusion on this panel is beneficial as this STR was downgraded in 2020 due to omission from expert provided lists for this panel.

Currently this STR is only included as part of the R54 Hereditary ataxia with onset in adulthood GMS panel (v7.0).
Adult onset neurodegenerative disorder v7.1 NOP56_GGCCTG Arina Puzriakova Tag Q3_24_promote_green tag was added to STR: NOP56_GGCCTG.
Tag Q3_24_expert_review tag was added to STR: NOP56_GGCCTG.
Hereditary neuropathy or pain disorder v6.10 NOP56_GGCCTG Arina Puzriakova Tag Q3_24_promote_green tag was added to STR: NOP56_GGCCTG.
Tag Q3_24_NHS_review tag was added to STR: NOP56_GGCCTG.
Tag Q3_24_expert_review tag was added to STR: NOP56_GGCCTG.
Hereditary neuropathy or pain disorder v6.10 NOP56_GGCCTG Arina Puzriakova commented on STR: NOP56_GGCCTG: Gene entity was recently added by Alexander Rossor (UCL Institute of Neurology) indicating that NOP56 should be green on this panel (https://panelapp.genomicsengland.co.uk/panels/846/gene/NOP56/). Adding STR as mechanism of disease is repeat expansions (GGCCTG)n rather than SNVs.

Heterozygous expansion of an intronic GGCCTG hexanucleotide repeat in the NOP56 gene causes spinocerebellar ataxia-36 (SCA36), an adult-onset slowly progressive neurodegenerative disorder. EMG in cases with skeletal muscle atrophy has shown neurogenic changes, indicating a lower motor neuropathy (PMID: 21683323). Flagging for additional GMS review to determine whether inclusion on this panel is beneficial.

Currently this STR is only included as part of the R54 Hereditary ataxia with onset in adulthood GMS panel (v7.0).
Hereditary neuropathy or pain disorder v6.10 NOP56_GGCCTG Arina Puzriakova Entity copied from Hereditary neuropathy v1.489
Hereditary neuropathy or pain disorder v6.10 NOP56_GGCCTG Arina Puzriakova STR: NOP56_GGCCTG was added
STR: NOP56_GGCCTG was added to Hereditary neuropathy or pain disorder. Sources: NHS GMS,Expert Review Amber,Expert Review
STR tags were added to STR: NOP56_GGCCTG.
Mode of inheritance for STR: NOP56_GGCCTG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for STR: NOP56_GGCCTG were set to Spinocerebellar ataxia 36, OMIM:614153
Hereditary neuropathy or pain disorder v6.9 NOP56 Arina Puzriakova Classified gene: NOP56 as Red List (low evidence)
Hereditary neuropathy or pain disorder v6.9 NOP56 Arina Puzriakova Added comment: Comment on list classification: Added to this panel by Alexander Rossor (UCL Institute of Neurology). Good evidence but mechanism of disease is repeat expansions (GGCCTG)n rather than SNVs and so rating the gene entity as Red. Added STR entity instead.
Hereditary neuropathy or pain disorder v6.9 NOP56 Arina Puzriakova Gene: nop56 has been classified as Red List (Low Evidence).
Intellectual disability v8.4 NOP56 Arina Puzriakova Mode of inheritance for gene: NOP56 was changed from Other to Other
Hereditary neuropathy or pain disorder v6.8 NOP56 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: NOP56.
Tag currently-ngs-unreportable tag was added to gene: NOP56.
Hereditary neuropathy or pain disorder v6.8 NOP56 Arina Puzriakova Mode of inheritance for gene: NOP56 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Hereditary neuropathy or pain disorder v6.7 NOP56 Arina Puzriakova Phenotypes for gene: NOP56 were changed from ataxia; motor neuropathy to Spinocerebellar ataxia 36, OMIM:614153
Hereditary neuropathy or pain disorder v6.6 PLA2G6 Arina Puzriakova Phenotypes for gene: PLA2G6 were changed from Neurodegeneration with brain iron accumulation; peripheral neuropathy to Neurodegeneration with brain iron accumulation 2B, OMIM:610217; Infantile neuroaxonal dystrophy 1, OMIM:256600
Hereditary neuropathy or pain disorder v6.5 PLA2G6 Arina Puzriakova Publications for gene: PLA2G6 were set to 18443314: 16783378:
Hereditary neuropathy or pain disorder v6.4 PLA2G6 Arina Puzriakova Classified gene: PLA2G6 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.4 PLA2G6 Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Alexander Rossor (UCL Institute of Neurology). Biallelic variant in PLA2G6 are associated with multiple neurodegenerative phenotypes with overlapping clinical and radiologic features including Infantile neuroaxonal dystrophy (MIM# 256600), Neurodegeneration with brain iron accumulation (MIM# 610217) and Parkinson disease (MIM# 612953). Although not universal, progressive motor axonal neuropathy has been reported as an early feature in multiple patients harbouring PLA2G6 variants (PMID: 18443314; 25164370; 27882168; 29859652; 30340910). Neuropathy can present earlier than other typical features such as iron accumulation in the brain and has represented the main diagnostic feature in some cases. Therefore, there is sufficient evidence to promote this gene to Green at the next GMS panel update.
Hereditary neuropathy or pain disorder v6.4 PLA2G6 Arina Puzriakova Gene: pla2g6 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.3 PLA2G6 Arina Puzriakova Tag Q3_24_promote_green tag was added to gene: PLA2G6.
Tag Q3_24_NHS_review tag was added to gene: PLA2G6.
Hereditary neuropathy or pain disorder v6.3 PIEZO2 Arina Puzriakova Publications for gene: PIEZO2 were set to 27653382
Hereditary neuropathy or pain disorder v6.2 PIEZO2 Arina Puzriakova Classified gene: PIEZO2 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v6.2 PIEZO2 Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Alexander Rossor (UCL Institute of Neurology). Biallelic variants cause distal arthrogryposis with impaired proprioception and touch. Mild sensory axonal neuropathy has been reported in some individuals (PMID: 27653382; 27843126; 27974811). Sufficient unrelated cases to promote this gene to Green at the next GMS panel update.

Neuropathy is not a feature of dominant phenotypes associated with PIEZO2.
Hereditary neuropathy or pain disorder v6.2 PIEZO2 Arina Puzriakova Gene: piezo2 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v6.1 PIEZO2 Arina Puzriakova Tag Q3_24_promote_green tag was added to gene: PIEZO2.
Tag Q3_24_NHS_review tag was added to gene: PIEZO2.
Possible mitochondrial disorder - nuclear genes v3.110 TOMM7 Eleanor Williams commented on gene: TOMM7: This gene was initially added to the Skeletal dysplasia panel. TOMM7 is a nuclear gene that encodes a subunit of the translocase of the outer mitochondrial membrane.
Skeletal dysplasia v7.4 TOMM7 Eleanor Williams Publications for gene: TOMM7 were set to PMID: 36282599; PMID: 36299998
Possible mitochondrial disorder - nuclear genes v3.110 TOMM7 Eleanor Williams Publications for gene: TOMM7 were set to PMID: 36282599; PMID: 36299998
Possible mitochondrial disorder - nuclear genes v3.109 TOMM7 Eleanor Williams Entity copied from Skeletal dysplasia v7.3
Possible mitochondrial disorder - nuclear genes v3.109 TOMM7 Eleanor Williams gene: TOMM7 was added
gene: TOMM7 was added to Possible mitochondrial disorder - nuclear genes. Sources: Literature,Expert Review Amber
Q3_24_promote_green, Q3_24_NHS_review tags were added to gene: TOMM7.
Mode of inheritance for gene: TOMM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TOMM7 were set to PMID: 36282599; PMID: 36299998
Phenotypes for gene: TOMM7 were set to Garg-Mishra progeroid syndrome, OMIM:620601; Garg-Mishra progeroid syndrome, MONDO:0957953
Skeletal dysplasia v7.3 TOMM7 Eleanor Williams Phenotypes for gene: TOMM7 were changed from Garg-Mishra progeroid syndrome; dwarfism; mandibular hypoplasia; microphthalmia; hyperopia; partial lipodystrophy to Garg-Mishra progeroid syndrome, OMIM:620601; Garg-Mishra progeroid syndrome, MONDO:0957953
Skeletal dysplasia v7.2 TOMM7 Eleanor Williams Deleted their comment
Skeletal dysplasia v7.2 TOMM7 Eleanor Williams changed review comment from: Associated with Garg-Mishra progeroid syndrome, 620601 (AR) in OMIM.

As reviewer Hannah Knight states, 2 cases reported with different homozygous missense variants in TOMM7:

PMID: 36282599 - Garg et al 2022, man of Chinese ancestry with an autosomal recessive form of progeria, characterized by severe proportionate short stature with relative macrocephaly, dysmorphisms and significant learning disabilities. The variant c.86C>T; p.Pro29Leu) in TOMM7 was found in a homozygous state in the proband, while parents and unaffected siblings were heterozyous. Functional studies showed reduced interactions between the mutant protein and core TOMM complex proteins in patient fibroblasts, aswell as increased mitochondrial oxygen consumption compared to control cells

PMID: 36299998. Young et al 2022 - report a Japanese patient with a TOMM7 homozygous variant (c.73T>C, p.Trp25Arg). The proband presented with a syndromic short stature, skeletal abnormalities, muscle hypotonia, microvesicular liver steatosis, and developmental delay. Results of studies with mouse models of TOMM7 deletion and also with knockin with the same variant suggest that the missense variant causes partial loss of Tomm7 function, producing a milder but still lethal phenotype compared to deletion.

A 3rd case is reported in PMID: 39333057 Yeole et al 2024 in which a homozygous splice variant c.153-2A > C in TOMM7 (NM_019059.5) was identified. The consanguineous parents were heterozygous for this variant. 2 siblings died after 52 days and 4 months of life respectively. Exome analysis was from the older sibling. In this case the phenotype was of neonatal-onset hypotonia, lactic acidosis, optic atrophy, and neuroimaging results suggestive of Leigh disease. Additionally Additionally, a known missense variant c.186G > C p.(Arg62Ser) in exon 3 of CASR (NM_001178065.2) was identified in causing hyperparathyroidism. No skeletal examination was performed.; to: Associated with Garg-Mishra progeroid syndrome, 620601 (AR) in OMIM.

As reviewer Hannah Knight states, 2 cases reported with different homozygous missense variants in TOMM7:

PMID: 36282599 - Garg et al 2022, man of Chinese ancestry with an autosomal recessive form of progeria, characterized by severe proportionate short stature with relative macrocephaly, dysmorphisms and significant learning disabilities. The variant c.86C>T; p.Pro29Leu) in TOMM7 was found in a homozygous state in the proband, while parents and unaffected siblings were heterozyous. Functional studies showed reduced interactions between the mutant protein and core TOMM complex proteins in patient fibroblasts, aswell as increased mitochondrial oxygen consumption compared to control cells

PMID: 36299998. Young et al 2022 - report a Japanese patient with a TOMM7 homozygous variant (c.73T>C, p.Trp25Arg). The proband presented with a syndromic short stature, skeletal abnormalities, muscle hypotonia, microvesicular liver steatosis, and developmental delay. Results of studies with mouse models of TOMM7 deletion and also with knockin with the same variant suggest that the missense variant causes partial loss of Tomm7 function, producing a milder but still lethal phenotype compared to deletion. In addition, analysis of tibial growth plates in mutant mice showed shortening of the growth plate, suggesting reduced chondrocyte proliferation which could lead to the skeletal phenotype.

A 3rd case is reported in PMID: 39333057 Yeole et al 2024 in which a homozygous splice variant c.153-2A > C in TOMM7 (NM_019059.5) was identified. The consanguineous parents were heterozygous for this variant. 2 siblings died after 52 days and 4 months of life respectively. Exome analysis was from the older sibling. In this case the phenotype was of neonatal-onset hypotonia, lactic acidosis, optic atrophy, and neuroimaging results suggestive of Leigh disease. Additionally, a known missense variant c.186G > C p.(Arg62Ser) in exon 3 of CASR (NM_001178065.2) was identified in causing hyperparathyroidism. No skeletal examination was performed.
Skeletal dysplasia v7.2 TOMM7 Eleanor Williams Classified gene: TOMM7 as Amber List (moderate evidence)
Skeletal dysplasia v7.2 TOMM7 Eleanor Williams Added comment: Comment on list classification: 2 cases reported with a skeletal phenotype with additional functional evidence for pathogenicity for the missense variants. A 3rd case with with a homozyous splice variant reports a more severe phenotype, with no skeletal phenotype recorded but earlier death.

Recommend green rating following GMS approval.
Skeletal dysplasia v7.2 TOMM7 Eleanor Williams Gene: tomm7 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v7.2 TOMM7 Eleanor Williams Classified gene: TOMM7 as Amber List (moderate evidence)
Skeletal dysplasia v7.2 TOMM7 Eleanor Williams Added comment: Comment on list classification: 2 cases reported with a skeletal phenotype with additional functional evidence for pathogenicity for the missense variants. A 3rd case with with a homozyous splice variant reports a more severe phenotype, with no skeletal phenotype recorded but earlier death.

Recommend green rating following GMS approval.
Skeletal dysplasia v7.2 TOMM7 Eleanor Williams Gene: tomm7 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v7.1 TOMM7 Eleanor Williams Tag Q3_24_promote_green tag was added to gene: TOMM7.
Tag Q3_24_NHS_review tag was added to gene: TOMM7.
Skeletal dysplasia v7.1 TOMM7 Eleanor Williams commented on gene: TOMM7
Paediatric disorders v60.10 Arina Puzriakova Panel version 60.9 has been signed off on 2024-10-30
Unexplained young onset end-stage renal disease v7.11 Eleanor Williams Panel version 7.10 has been signed off on 2024-10-30
Hereditary ataxia and cerebellar anomalies - childhood onset v19.4 Achchuthan Shanmugasundram Panel version 19.3 has been signed off on 2024-10-30
Cystic renal disease v10.4 Achchuthan Shanmugasundram Panel version 10.3 has been signed off on 2024-10-30
Childhood onset leukodystrophy v26.7 Achchuthan Shanmugasundram Panel version 26.6 has been signed off on 2024-10-30
Unexplained death in infancy and sudden unexplained death in childhood v16.7 Eleanor Williams Panel version 16.6 has been signed off on 2024-10-30
Other rare neuromuscular disorders v26.6 Arina Puzriakova Panel version 26.5 has been signed off on 2024-10-30
Hypotonic infant v38.8 Arina Puzriakova Panel version 38.7 has been signed off on 2024-10-30
Cerebral malformation v15.4 Achchuthan Shanmugasundram Panel version 15.3 has been signed off on 2024-10-30
Rare multisystem ciliopathy Super panel v17.5 Eleanor Williams Panel version 17.4 has been signed off on 2024-10-30
Brugada syndrome and cardiac sodium channel disease v3.12 Sarah Leigh Panel version 3.11 has been signed off on 2024-10-30
Proteinuric renal disease v4.16 Sarah Leigh Panel version 4.15 has been signed off on 2024-10-30
Haematuria v2.15 Sarah Leigh Panel version 2.14 has been signed off on 2024-10-30
Arrhythmogenic right ventricular cardiomyopathy v3.13 Sarah Leigh Panel version 3.12 has been signed off on 2024-10-30
Dilated and arrhythmogenic cardiomyopathy v2.33 Sarah Leigh Panel version 2.32 has been signed off on 2024-10-30
Hypertrophic cardiomyopathy v4.17 Sarah Leigh Panel version 4.16 has been signed off on 2024-10-30
Short QT syndrome v3.14 Sarah Leigh Panel version 3.13 has been signed off on 2024-10-30
Catecholaminergic polymorphic VT v5.1 Sarah Leigh Panel version 5.0 has been signed off on 2024-10-30
Catecholaminergic polymorphic VT v5.0 Sarah Leigh promoted panel to version 5.0
Intellectual disability v8.3 Arina Puzriakova Panel version 8.0 has been signed off on 2024-10-30
Progressive cardiac conduction disease v2.10 Eleanor Williams Panel version 2.9 has been signed off on 2024-10-30
Nephrocalcinosis or nephrolithiasis v4.17 Eleanor Williams Panel version 4.16 has been signed off on 2024-10-30
Hereditary systemic amyloidosis v1.23 Eleanor Williams Panel version 1.22 has been signed off on 2024-10-30
Tubulointerstitial kidney disease v3.5 Eleanor Williams Panel version 3.4 has been signed off on 2024-10-30
Renal tubulopathies v4.19 Eleanor Williams Panel version 4.18 has been signed off on 2024-10-30
Membranoproliferative glomerulonephritis including C3 glomerulopathy v3.5 Eleanor Williams Panel version 3.4 has been signed off on 2024-10-30
Atypical haemolytic uraemic syndrome v3.5 Arina Puzriakova Panel version 3.4 has been signed off on 2024-10-30
Long QT syndrome v3.10 Arina Puzriakova Panel version 3.9 has been signed off on 2024-10-30
Skeletal ciliopathies v5.2 Achchuthan Shanmugasundram Panel version 5.1 has been signed off on 2024-10-30
Paediatric motor neuronopathies v3.9 Arina Puzriakova Panel version 3.8 has been signed off on 2024-10-30
Ophthalmological ciliopathies v4.6 Arina Puzriakova Panel version 4.5 has been signed off on 2024-10-30
Limb disorders v6.3 Arina Puzriakova Panel version 6.2 has been signed off on 2024-10-30
Rhabdomyolysis and metabolic muscle disorders v5.2 Achchuthan Shanmugasundram Panel version 5.1 has been signed off on 2024-10-30
Congenital disorders of glycosylation v6.8 Arina Puzriakova Panel version 6.7 has been signed off on 2024-10-30
Clefting v6.4 Arina Puzriakova Panel version 6.3 has been signed off on 2024-10-30
Renal ciliopathies v3.14 Achchuthan Shanmugasundram Panel version 3.13 has been signed off on 2024-10-30
Holoprosencephaly v5.2 Achchuthan Shanmugasundram Panel version 5.1 has been signed off on 2024-10-30
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v4.38 Achchuthan Shanmugasundram Panel version 4.37 has been signed off on 2024-10-30
Bilateral congenital or childhood onset cataracts v6.1 Sarah Leigh Panel version 6.0 has been signed off on 2024-10-30
Bilateral congenital or childhood onset cataracts v6.0 Sarah Leigh promoted panel to version 6.0
Congenital myaesthenic syndrome v4.9 Achchuthan Shanmugasundram Panel version 4.8 has been signed off on 2024-10-30
Neurological segmental overgrowth v3.1 Arina Puzriakova Panel version 3.0 has been signed off on 2024-10-30
Neurological segmental overgrowth v3.0 Arina Puzriakova promoted panel to version 3.0
Intellectual disability v8.2 Sarah Leigh Panel signed off version 8.0 has been removed
Monogenic hearing loss v4.58 Achchuthan Shanmugasundram Panel version 4.57 has been signed off on 2024-10-30
Neurological ciliopathies v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2024-10-30
Intellectual disability v8.1 Sarah Leigh Panel version 8.0 has been signed off on 2024-10-30
Neurological ciliopathies v5.0 Arina Puzriakova promoted panel to version 5.0
White matter disorders and cerebral calcification - narrow panel v6.1 Achchuthan Shanmugasundram Panel version 6.0 has been signed off on 2024-10-30
Mitochondrial disorders v8.1 Arina Puzriakova Panel version 8.0 has been signed off on 2024-10-30
White matter disorders and cerebral calcification - narrow panel v6.0 Achchuthan Shanmugasundram promoted panel to version 6.0
Mitochondrial disorders v8.0 Arina Puzriakova promoted panel to version 8.0
Intellectual disability v8.0 Sarah Leigh promoted panel to version 8.0
Childhood onset hereditary spastic paraplegia v7.1 Eleanor Williams Panel version 7.0 has been signed off on 2024-10-30
Childhood onset hereditary spastic paraplegia v7.0 Eleanor Williams promoted panel to version 7.0
Fetal anomalies v5.1 Sarah Leigh Panel version 5.0 has been signed off on 2024-10-30
Unexplained young onset end-stage renal disease - additional genes v1.1 Achchuthan Shanmugasundram Panel version 1.0 has been signed off on 2024-10-30
Fetal anomalies v5.0 Sarah Leigh promoted panel to version 5.0
Malformations of cortical development v7.1 Arina Puzriakova Panel version 7.0 has been signed off on 2024-10-30
Unexplained young onset end-stage renal disease - additional genes v1.0 Achchuthan Shanmugasundram promoted panel to version 1.0
Malformations of cortical development v7.0 Arina Puzriakova promoted panel to version 7.0
Early onset or syndromic epilepsy v7.1 Eleanor Williams Panel version 7.0 has been signed off on 2024-10-30
Unexplained young onset end-stage renal disease - additional genes v0.131 Achchuthan Shanmugasundram Panel types changed to Component Of Super Panel; GMS signed-off
Primary immunodeficiency or monogenic inflammatory bowel disease v7.1 Sarah Leigh Panel version 7.0 has been signed off on 2024-10-30
Early onset or syndromic epilepsy v7.0 Eleanor Williams promoted panel to version 7.0
Primary immunodeficiency or monogenic inflammatory bowel disease v7.0 Sarah Leigh promoted panel to version 7.0
Distal myopathies v6.1 Arina Puzriakova Panel version 6.0 has been signed off on 2024-10-30
Likely inborn error of metabolism v7.1 Achchuthan Shanmugasundram Panel version 7.0 has been signed off on 2024-10-30
Adult onset neurodegenerative disorder v7.1 Eleanor Williams Panel version 7.0 has been signed off on 2024-10-30
Distal myopathies v6.0 Arina Puzriakova promoted panel to version 6.0
Adult onset neurodegenerative disorder v7.0 Eleanor Williams promoted panel to version 7.0
Paediatric or syndromic cardiomyopathy v6.1 Sarah Leigh Panel version 6.0 has been signed off on 2024-10-30
Childhood onset dystonia, chorea or related movement disorder v6.1 Eleanor Williams Panel version 6.0 has been signed off on 2024-10-30
Paediatric or syndromic cardiomyopathy v6.0 Sarah Leigh promoted panel to version 6.0
DDG2P v5.1 Arina Puzriakova Panel version 5.0 has been signed off on 2024-10-30
Childhood onset dystonia, chorea or related movement disorder v6.0 Eleanor Williams promoted panel to version 6.0
Likely inborn error of metabolism v7.0 Achchuthan Shanmugasundram promoted panel to version 7.0
DDG2P v5.0 Arina Puzriakova promoted panel to version 5.0
Hereditary ataxia with onset in adulthood v7.1 Eleanor Williams Panel version 7.0 has been signed off on 2024-10-30
Severe microcephaly v7.1 Achchuthan Shanmugasundram Panel version 7.0 has been signed off on 2024-10-30
Skeletal dysplasia v7.1 Sarah Leigh Panel version 7.0 has been signed off on 2024-10-30
Severe microcephaly v7.0 Achchuthan Shanmugasundram promoted panel to version 7.0
Hereditary ataxia with onset in adulthood v7.0 Eleanor Williams promoted panel to version 7.0
Cystic kidney disease v7.1 Arina Puzriakova Panel version 7.0 has been signed off on 2024-10-30
Skeletal dysplasia v7.0 Sarah Leigh promoted panel to version 7.0
Cystic kidney disease v7.0 Arina Puzriakova promoted panel to version 7.0
Arthrogryposis v8.1 Achchuthan Shanmugasundram Panel version 8.0 has been signed off on 2024-10-30
Arthrogryposis v8.0 Achchuthan Shanmugasundram promoted panel to version 8.0
Ataxia and cerebellar anomalies - narrow panel v7.1 Arina Puzriakova Panel version 7.0 has been signed off on 2024-10-30
Paediatric disorders - additional genes v6.1 Sarah Leigh Panel version 6.0 has been signed off on 2024-10-30
Ataxia and cerebellar anomalies - narrow panel v7.0 Arina Puzriakova promoted panel to version 7.0
Congenital myopathy v5.1 Achchuthan Shanmugasundram Panel version 5.0 has been signed off on 2024-10-30
NICE approved PARP inhibitor treatment v1.1 Eleanor Williams Panel version 1.0 has been signed off on 2024-10-30
NICE approved PARP inhibitor treatment v1.0 Eleanor Williams promoted panel to version 1.0
Congenital myopathy v5.0 Achchuthan Shanmugasundram promoted panel to version 5.0
NICE approved PARP inhibitor treatment v0.10 Eleanor Williams Panel status changed from internal to public
Panel types changed to GMS Rare Disease; GMS signed-off
Paediatric disorders - additional genes v6.0 Sarah Leigh promoted panel to version 6.0
Paediatric disorders - additional genes v6.0 Sarah Leigh promoted panel to version 6.0
Congenital muscular dystrophy v5.1 Achchuthan Shanmugasundram Panel version 5.0 has been signed off on 2024-10-30
Retinal disorders v7.1 Eleanor Williams Panel version 7.0 has been signed off on 2024-10-30
Congenital muscular dystrophy v5.0 Achchuthan Shanmugasundram promoted panel to version 5.0
Retinal disorders v7.0 Eleanor Williams promoted panel to version 7.0
Hereditary neuropathy or pain disorder v6.1 Achchuthan Shanmugasundram Panel version 6.0 has been signed off on 2024-10-30
Hereditary neuropathy or pain disorder v6.0 Achchuthan Shanmugasundram promoted panel to version 6.0
Hereditary neuropathy or pain disorder v5.107 PIEZO2 Arina Puzriakova Phenotypes for gene: PIEZO2 were changed from arthrodryposis; sensory neuropathy to Arthrogryposis, distal, with impaired proprioception and touch, OMIM:617146
Unexplained young onset end-stage renal disease v5.35 Achchuthan Shanmugasundram Changed child panels to: Cystic kidney disease; Renal tubulopathies; Nephrocalcinosis or nephrolithiasis; Proteinuric renal disease; Renal ciliopathies; Tubulointerstitial kidney disease; Membranoproliferative glomerulonephritis including C3 glomerulopathy; Atypical haemolytic uraemic syndrome; Haematuria; Hereditary systemic amyloidosis; Unexplained young onset end-stage renal disease - additional genes
Unexplained young onset end-stage renal disease - additional genes v0.129 Achchuthan Shanmugasundram Panel status changed from internal to public
Unexplained young onset end-stage renal disease v5.34 Achchuthan Shanmugasundram Changed child panels to: Cystic kidney disease; Renal tubulopathies; Nephrocalcinosis or nephrolithiasis; Proteinuric renal disease; Renal ciliopathies; Tubulointerstitial kidney disease; Membranoproliferative glomerulonephritis including C3 glomerulopathy; Atypical haemolytic uraemic syndrome; Haematuria; Hereditary systemic amyloidosis
Panel types changed to GMS Rare Disease Virtual; Super Panel; GMS Rare Disease; GMS signed-off
Hereditary systemic amyloidosis v1.22 Arina Puzriakova Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Haematuria v2.14 Arina Puzriakova Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Renal tubulopathies v4.18 Eleanor Williams Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Atypical haemolytic uraemic syndrome v3.4 Arina Puzriakova Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Proteinuric renal disease v4.15 Eleanor Williams Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; Component Of Super Panel; GMS signed-off
Arthrogryposis v7.6 Arina Puzriakova List of related panels changed from Arthrogrythsis; R83 to R83
Nephrocalcinosis or nephrolithiasis v4.16 Eleanor Williams Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Tubulointerstitial kidney disease v3.4 Achchuthan Shanmugasundram Panel types changed to GMS Rare Disease; Component Of Super Panel; GMS signed-off
Membranoproliferative glomerulonephritis including C3 glomerulopathy v3.4 Eleanor Williams Panel types changed to Rare Disease 100K; GMS Rare Disease Virtual; GMS Rare Disease; Component Of Super Panel; GMS signed-off
Congenital myopathy v4.44 ZC4H2 Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing tag was added to gene: ZC4H2.
Congenital myopathy v4.44 UNC45B Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing tag was added to gene: UNC45B.
Congenital myopathy v4.44 TRDN Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing tag was added to gene: TRDN.
Congenital myopathy v4.44 SPTBN4 Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing tag was added to gene: SPTBN4.
Congenital myopathy v4.44 MLIP Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing tag was added to gene: MLIP.
Congenital myopathy v4.44 LETM1 Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing tag was added to gene: LETM1.
Congenital myopathy v4.44 KY Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing tag was added to gene: KY.
Congenital myopathy v4.44 GBE1 Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing tag was added to gene: GBE1.
Congenital myopathy v4.44 DNAJB4 Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing tag was added to gene: DNAJB4.
Congenital myopathy v4.44 COL25A1 Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing tag was added to gene: COL25A1.
Congenital myopathy v4.44 COL13A1 Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing tag was added to gene: COL13A1.
Congenital myopathy v4.44 ASCC1 Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing tag was added to gene: ASCC1.
Congenital muscular dystrophy v4.29 POGLUT1 Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing tag was added to gene: POGLUT1.
Congenital muscular dystrophy v4.29 GOSR2 Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing tag was added to gene: GOSR2.
Congenital muscular dystrophy v4.29 GOLGA2 Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing tag was added to gene: GOLGA2.
Congenital muscular dystrophy v4.29 EMD Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing tag was added to gene: EMD.
Congenital muscular dystrophy v4.29 DTNA Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing tag was added to gene: DTNA.
Congenital muscular dystrophy v4.29 DPM3 Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing tag was added to gene: DPM3.
Congenital muscular dystrophy v4.29 BET1 Achchuthan Shanmugasundram Tag currently-not-available-via-GLH-non-WGS-testing tag was added to gene: BET1.
Early onset or syndromic epilepsy v6.15 CCDC88A Cassandra Smith reviewed gene: CCDC88A: Rating: GREEN; Mode of pathogenicity: None; Publications: 39334473, 37798908, 26917597; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
DDG2P v4.15 MSL2 Arina Puzriakova Tag gene-checked was removed from gene: MSL2.
Intellectual disability v7.67 MSL2 Arina Puzriakova Phenotypes for gene: MSL2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to Karayol-Borroto-Haghshenas neurodevelopmental syndrome, OMIM:620985
Optic neuropathy v4.35 BORCS8 Arina Puzriakova Tag gene-checked was removed from gene: BORCS8.
Tag Q3_24_promote_green tag was added to gene: BORCS8.
Intellectual disability v7.66 BORCS8 Arina Puzriakova Phenotypes for gene: BORCS8 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to Neurodegeneration, infantile-onset, with optic atrophy and brain abnormalities, OMIM:620987
Early onset or syndromic epilepsy v6.15 BORCS8 Arina Puzriakova Phenotypes for gene: BORCS8 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to Neurodegeneration, infantile-onset, with optic atrophy and brain abnormalities, OMIM:620987
Intellectual disability v7.65 BORCS8 Arina Puzriakova Tag gene-checked was removed from gene: BORCS8.
Early onset or syndromic epilepsy v6.14 BORCS8 Arina Puzriakova Tag gene-checked was removed from gene: BORCS8.
DDG2P v4.15 BORCS8 Arina Puzriakova Tag gene-checked was removed from gene: BORCS8.
Childhood onset hereditary spastic paraplegia v6.11 BORCS8 Arina Puzriakova Phenotypes for gene: BORCS8 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to Neurodegeneration, infantile-onset, with optic atrophy and brain abnormalities, OMIM:620987
Childhood onset hereditary spastic paraplegia v6.10 BORCS8 Arina Puzriakova Tag gene-checked was removed from gene: BORCS8.
Optic neuropathy v4.35 BORCS8 Arina Puzriakova Phenotypes for gene: BORCS8 were changed from neurodevelopmental disorder, MONDO:0700092; hereditary optic neuropathy, MONDO:0020249 to Neurodegeneration, infantile-onset, with optic atrophy and brain abnormalities, OMIM:620987
Optic neuropathy v4.34 BORCS8 Arina Puzriakova Tag Q3_24_promote_green was removed from gene: BORCS8.
Monogenic short stature v1.1 CENPJ Arina Puzriakova Tag new-gene-name tag was added to gene: CENPJ.
Intellectual disability v7.65 CENPJ Arina Puzriakova Tag new-gene-name tag was added to gene: CENPJ.
Monogenic short stature v1.1 CENPJ Arina Puzriakova commented on gene: CENPJ
Intellectual disability v7.65 CENPJ Arina Puzriakova commented on gene: CENPJ
DDG2P v4.15 CENPJ Arina Puzriakova commented on gene: CENPJ
DDG2P v4.15 CENPJ Arina Puzriakova Tag new-gene-name tag was added to gene: CENPJ.
Fetal anomalies v4.198 CENPJ Arina Puzriakova Tag new-gene-name tag was added to gene: CENPJ.
Fetal anomalies v4.198 CENPJ Arina Puzriakova commented on gene: CENPJ
Severe microcephaly v6.8 CENPJ Arina Puzriakova commented on gene: CENPJ
Severe microcephaly v6.8 CENPJ Arina Puzriakova Tag new-gene-name tag was added to gene: CENPJ.
Cerebral vascular malformations v3.16 CENPJ Arina Puzriakova commented on gene: CENPJ
Cerebral vascular malformations v3.16 CENPJ Arina Puzriakova Tag new-gene-name tag was added to gene: CENPJ.
IUGR and IGF abnormalities v1.69 CENPJ Arina Puzriakova Tag new-gene-name tag was added to gene: CENPJ.
IUGR and IGF abnormalities v1.69 CENPJ Arina Puzriakova commented on gene: CENPJ
Rare multisystem ciliopathy disorders v1.174 CCDC103 Arina Puzriakova Tag new-gene-name tag was added to gene: CCDC103.
Intellectual disability v7.65 CCDC103 Arina Puzriakova Tag new-gene-name tag was added to gene: CCDC103.
DDG2P v4.15 CCDC103 Arina Puzriakova Tag new-gene-name tag was added to gene: CCDC103.
Fetal anomalies v4.198 CCDC103 Arina Puzriakova Tag new-gene-name tag was added to gene: CCDC103.
Respiratory ciliopathies including non-CF bronchiectasis v3.19 CCDC103 Arina Puzriakova Tag new-gene-name tag was added to gene: CCDC103.
Laterality disorders and isomerism v3.17 CCDC103 Arina Puzriakova Tag new-gene-name tag was added to gene: CCDC103.
Rare multisystem ciliopathy disorders v1.174 CCDC103 Arina Puzriakova commented on gene: CCDC103
Intellectual disability v7.65 CCDC103 Arina Puzriakova commented on gene: CCDC103: Added new-gene-name tag, new approved HGNC gene symbol for CCDC103 is DNAAF19.
DDG2P v4.15 CCDC103 Arina Puzriakova commented on gene: CCDC103
Fetal anomalies v4.198 CCDC103 Arina Puzriakova commented on gene: CCDC103
Laterality disorders and isomerism v3.17 CCDC103 Arina Puzriakova commented on gene: CCDC103
Respiratory ciliopathies including non-CF bronchiectasis v3.19 CCDC103 Arina Puzriakova commented on gene: CCDC103
Primary ciliary disorders v1.42 CCDC103 Arina Puzriakova commented on gene: CCDC103
Primary ciliary disorders v1.42 CCDC103 Arina Puzriakova Tag new-gene-name tag was added to gene: CCDC103.
Unexplained young onset end-stage renal disease - additional genes v0.128 Achchuthan Shanmugasundram Panel status changed from public to internal
NICE approved PARP inhibitor treatment v0.9 Achchuthan Shanmugasundram Panel status changed from public to internal
Hereditary neuropathy or pain disorder v5.106 MFF Achchuthan Shanmugasundram Classified gene: MFF as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v5.106 MFF Achchuthan Shanmugasundram Added comment: Comment on list classification: There are only two patients reported with neuropathy so far. Hence, this gene should be rated amber with current evidence.
Hereditary neuropathy or pain disorder v5.106 MFF Achchuthan Shanmugasundram Gene: mff has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v5.105 MFF Achchuthan Shanmugasundram Phenotypes for gene: MFF were changed from encephalopathy; developmental delay; peripheral neuropathy in some to Encephalopathy due to defective mitochondrial and peroxisomal fission 2, OMIM:617086
Hereditary neuropathy or pain disorder v5.104 MFF Achchuthan Shanmugasundram Deleted their comment
Hereditary neuropathy or pain disorder v5.104 MFF Achchuthan Shanmugasundram commented on gene: MFF: PMID:26783368 reported three patients from two unrelated families with EMPF2 and with biallelic MFF variants. Patient 1 (an Austrian boy) was identified with compound heterozygous variants (p.Leu62Profs*13; p.Arg298Ter) and had mixed form of peripheral neuropathy shown on compound muscle action potential. Patient 3 (one of two Turkish siblings) had phenotype consistent with demyelinating peripheral neuropathy, which was absent in his brother. They had homozygous p.Glu153Alafs*5 variants.

Although EMPF2 was reported in other patients (PMIDs: 22499341; 32181496; 34750646), neuropathy was not reported in them.
Hereditary neuropathy or pain disorder v5.104 MFF Achchuthan Shanmugasundram reviewed gene: MFF: Rating: AMBER; Mode of pathogenicity: None; Publications: 26783368; Phenotypes: Encephalopathy due to defective mitochondrial and peroxisomal fission 2, OMIM:617086; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Unexplained young onset end-stage renal disease - additional genes v0.127 Achchuthan Shanmugasundram Panel status changed from internal to public
NICE approved PARP inhibitor treatment v0.8 Achchuthan Shanmugasundram Panel status changed from internal to public
Intellectual disability v7.65 TBCE Eleanor Williams Phenotypes for gene: TBCE were changed from Kenny-Caffey syndrome-1, 244460Hypoparathyroidism-retardation-dysmorphism syndrome, 241410; KENNY-CAFFEY SYNDROME TYPE 1 (KCS1) to Kenny-Caffey syndrome, type 1, OMIM:244460; autosomal recessive Kenny-Caffey syndrome, MONDO:0009486; Hypoparathyroidism-retardation-dysmorphism syndrome, OMIM:241410; hypoparathyroidism-retardation-dysmorphism syndrome, MONDO:0009426
Hereditary neuropathy or pain disorder v5.104 MAPK8IP3 Eleanor Williams commented on gene: MAPK8IP3: Awaiting clinical feedback before deciding on rating.
Hereditary neuropathy or pain disorder v5.104 MAPK8IP3 Eleanor Williams reviewed gene: MAPK8IP3: Rating: AMBER; Mode of pathogenicity: None; Publications: 37462082, 30945334, 30612693; Phenotypes: Neurodevelopmental disorder with or without variable brain abnormalities, OMIM:618443, neurodevelopmental disorder with or without variable brain abnormalities, NEDBA, MONDO:0032755; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
White matter disorders and cerebral calcification - narrow panel v5.3 HPDL Eleanor Williams Tag Q3_24_promote_green tag was added to gene: HPDL.
Hereditary neuropathy or pain disorder v5.104 HPDL Eleanor Williams Tag Q3_24_promote_green tag was added to gene: HPDL.
Tag Q3_24_NHS_review tag was added to gene: HPDL.
Hereditary neuropathy or pain disorder v5.104 HPDL Eleanor Williams Phenotypes for gene: HPDL were changed from developmental delay; spastic paraplegia; peripheral neuropathy to Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, OMIM:619026; Spastic paraplegia 83, autosomal recessive, OMIM:619027; neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, MONDO:0033613; spastic paraplegia 83, autosomal recessive, MONDO:0033614
Hereditary neuropathy or pain disorder v5.103 HPDL Eleanor Williams Classified gene: HPDL as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v5.103 HPDL Eleanor Williams Added comment: Comment on list classification: On recommendation of clinical expert this gene has been promoted to amber and has been tagged for promotion to green subject to GMS review.
Hereditary neuropathy or pain disorder v5.103 HPDL Eleanor Williams Gene: hpdl has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v5.102 HPDL Eleanor Williams reviewed gene: HPDL: Rating: GREEN; Mode of pathogenicity: None; Publications: 32707086; Phenotypes: Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, OMIM:619026, Spastic paraplegia 83, autosomal recessive, OMIM:619027, neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, MONDO:0033613, spastic paraplegia 83, autosomal recessive, MONDO:0033614; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v5.8 FA2H Eleanor Williams Phenotypes for gene: FA2H were changed from fatty acid hydroxylase-associated neurodegeneration; Dystonia; Spastic paraplegia 35, autosomal recessive 612319 to fatty acid hydroxylase-associated neurodegeneration; Dystonia; Spastic paraplegia 35, autosomal recessive, OMIM:612319; hereditary spastic paraplegia 35, MONDO:0012866
Likely inborn error of metabolism v6.23 FA2H Eleanor Williams Phenotypes for gene: FA2H were changed from Spastic paraplegia 35, autosomal recessive, OMIM:612319; hereditary spastic paraplegia 35, MONDO:0012866 to Spastic paraplegia 35, autosomal recessive, OMIM:612319; hereditary spastic paraplegia 35, MONDO:0012866
Likely inborn error of metabolism v6.22 FA2H Eleanor Williams Phenotypes for gene: FA2H were changed from Spastic paraplegia 35, autosomal recessive, OMIM:612319; hereditary spastic paraplegia 35, MONDO:0012866 to Spastic paraplegia 35, autosomal recessive, OMIM:612319; hereditary spastic paraplegia 35, MONDO:0012866
Likely inborn error of metabolism v6.22 FA2H Eleanor Williams Phenotypes for gene: FA2H were changed from Fatty acid 2-hydroxylase deficiency (Disorders of complex lipid synthesis); Early onset dystonia; Neurodegeneration with brain iron accumulation (NBIA) (Disorder of iron metabolism); Hereditary spastic paraplegia to Spastic paraplegia 35, autosomal recessive, OMIM:612319; hereditary spastic paraplegia 35, MONDO:0012866
Adult onset hereditary spastic paraplegia v5.2 FA2H Eleanor Williams Phenotypes for gene: FA2H were changed from Spastic paraplegia 35, autosomal recessive, 611026 to Spastic paraplegia 35, autosomal recessive, OMIM:612319; hereditary spastic paraplegia 35, MONDO:0012866
Childhood onset hereditary spastic paraplegia v6.10 FA2H Eleanor Williams Phenotypes for gene: FA2H were changed from Spastic paraplegia 35, autosomal recessive, 612319 to Spastic paraplegia 35, autosomal recessive, OMIM:612319; hereditary spastic paraplegia 35, MONDO:0012866
Hereditary neuropathy or pain disorder v5.102 EXOSC3 Eleanor Williams Phenotypes for gene: EXOSC3 were changed from pontocerebellar hypoplasia; motor neuropathy to Pontocerebellar hypoplasia, type 1B, OMIM:614678; pontocerebellar hypoplasia type 1B, MONDO:0013853
Hereditary neuropathy or pain disorder v5.101 EXOSC3 Eleanor Williams Publications for gene: EXOSC3 were set to 23564332:24524299:25149867:12548734
Hereditary neuropathy or pain disorder v5.100 FA2H Eleanor Williams Phenotypes for gene: FA2H were changed from SPG35, Childhood onset spasticity, cognitive decline and leukodystrophy. Mild sensory axonal neuropathy on NCS. Epilepsy, dysphagia, dysarthria and dystonia also observed; Spastic paraplegia 35, autosomal recessive, 612319 to Spastic paraplegia 35, autosomal recessive, OMIM:612319; hereditary spastic paraplegia 35, MONDO:0012866
Hereditary neuropathy or pain disorder v5.99 FA2H Eleanor Williams Publications for gene: FA2H were set to 22146942
Hereditary neuropathy or pain disorder v5.98 FA2H Eleanor Williams Tag Q3_24_promote_green tag was added to gene: FA2H.
Tag Q3_24_NHS_review tag was added to gene: FA2H.
Hereditary neuropathy or pain disorder v5.98 FA2H Eleanor Williams Classified gene: FA2H as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v5.98 FA2H Eleanor Williams Added comment: Comment on list classification: Promoting with amber with a recommendation for green rating as there are now 4 cases with peripheral neuropathy and variants in this gene reported.
Hereditary neuropathy or pain disorder v5.98 FA2H Eleanor Williams Gene: fa2h has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v5.97 FA2H Eleanor Williams edited their review of gene: FA2H: Changed phenotypes to: Spastic paraplegia 35, autosomal recessive, OMIM:612319, hereditary spastic paraplegia 35, MONDO:0012866
Hereditary neuropathy or pain disorder v5.97 FA2H Eleanor Williams reviewed gene: FA2H: Rating: ; Mode of pathogenicity: None; Publications: 22146942, 31135052; Phenotypes: Spastic paraplegia 35, autosomal recessive, OMIM:612319; Mode of inheritance: None
Hereditary neuropathy or pain disorder v5.97 EXOSC3 Eleanor Williams Classified gene: EXOSC3 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v5.97 EXOSC3 Eleanor Williams Added comment: Comment on list classification: Promoting this gene to amber with a proposal to promote to green following NHS GMS review. There are sufficient cases with a relevant phenotype and variants in this gene.
Hereditary neuropathy or pain disorder v5.97 EXOSC3 Eleanor Williams Gene: exosc3 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v5.96 EXOSC3 Eleanor Williams Tag Q3_24_promote_green tag was added to gene: EXOSC3.
Tag Q3_24_NHS_review tag was added to gene: EXOSC3.
Hereditary neuropathy or pain disorder v5.96 EXOSC3 Eleanor Williams reviewed gene: EXOSC3: Rating: ; Mode of pathogenicity: None; Publications: 23564332, 24524299, 25149867, 12548734; Phenotypes: Pontocerebellar hypoplasia, type 1B, OMIM:614678, pontocerebellar hypoplasia type 1B, MONDO:0013853; Mode of inheritance: None
Hereditary neuropathy or pain disorder v5.96 PTRH2 Achchuthan Shanmugasundram Classified gene: PTRH2 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v5.96 PTRH2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Alexander Rossor, there are multiple unrelated individuals presenting with peripheral neuropathy. Hence, this gene can be promoted to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v5.96 PTRH2 Achchuthan Shanmugasundram Gene: ptrh2 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v5.95 PTRH2 Achchuthan Shanmugasundram Phenotypes for gene: PTRH2 were changed from Infantile-onset multisystem neurologic, endocrine, and pancreatic disease, 616263; Infantile-onset multisystem disease with intellectual disability, microcephaly, progressive ataxia, sensory neuronal hearing loss, hepatomegaly, pancreatic insufficiency, proximal placement of thumb, SNCV neuropathy to Infantile-onset multisystem neurologic, endocrine, and pancreatic disease, OMIM:616263
Hereditary neuropathy or pain disorder v5.94 PTRH2 Achchuthan Shanmugasundram Publications for gene: PTRH2 were set to 25572476; 25558065
Hereditary neuropathy or pain disorder v5.93 PTRH2 Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: PTRH2.
Tag Q3_24_NHS_review tag was added to gene: PTRH2.
Hereditary neuropathy or pain disorder v5.93 PTRH2 Achchuthan Shanmugasundram reviewed gene: PTRH2: Rating: GREEN; Mode of pathogenicity: None; Publications: 39176129; Phenotypes: Infantile-onset multisystem neurologic, endocrine, and pancreatic disease, OMIM:616263; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v5.93 PDHA1 Achchuthan Shanmugasundram Classified gene: PDHA1 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v5.93 PDHA1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Alexander Rossor, there is sufficient evidence available for the association of this gene with syndromic neuropathy and hence this gene can be promoted to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v5.93 PDHA1 Achchuthan Shanmugasundram Gene: pdha1 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v5.92 PDHA1 Achchuthan Shanmugasundram Tag Q3_24_NHS_review tag was added to gene: PDHA1.
Hereditary neuropathy or pain disorder v5.92 PDHA1 Achchuthan Shanmugasundram Phenotypes for gene: PDHA1 were changed from to Pyruvate dehydrogenase E1-alpha deficiency, OMIM:312170
Hereditary neuropathy or pain disorder v5.91 PDHA1 Achchuthan Shanmugasundram Publications for gene: PDHA1 were set to
Hereditary neuropathy or pain disorder v5.90 PDHA1 Achchuthan Shanmugasundram Mode of inheritance for gene: PDHA1 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)
Hereditary neuropathy or pain disorder v5.89 PDHA1 Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: PDHA1.
Hereditary neuropathy or pain disorder v5.89 PDHA1 Achchuthan Shanmugasundram reviewed gene: PDHA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33661577, 36693417, 38497591; Phenotypes: Pyruvate dehydrogenase E1-alpha deficiency, OMIM:312170; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Hereditary neuropathy or pain disorder v5.89 TBCE Arina Puzriakova Phenotypes for gene: TBCE were changed from encephalopathy; peripheral neuropathy to Encephalopathy, progressive, with amyotrophy and optic atrophy, OMIM:617207
Intellectual disability v7.64 TRMT5 Arina Puzriakova Tag Q3_24_NHS_review was removed from gene: TRMT5.
Intellectual disability v7.64 TRMT5 Arina Puzriakova changed review comment from: Comment on list classification: New gene added to the panel by Alexander Rossor (UCL Institute of Neurology). There is sufficient evidence to promote this gene to Green at the next GMS panel update.

Associated with relevant phenotype in OMIM, but not associated with phenotype in G2P. At least 3 variants reported in at least three cases, together with supportive functional studies.

Phenotype is characterised as a highly variable multisystemic disorder, ranging from hypotonia and GDD in infancy to exercise intolerance and muscle weakness in early adulthood. Peripheral neuropathy is a universal feature in all cases. Various other neurological features such as spasticity, cerebellar signs and seizures, and involvement of other organ systems, including the heart, pancreas, and kidney may also be observed.; to: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.

Associated with relevant phenotype in OMIM, but not associated with phenotype in G2P. At least 3 variants reported in at least three cases, together with supportive functional studies.

Phenotype is characterised as a highly variable multisystemic disorder, ranging from hypotonia and GDD in infancy to exercise intolerance and muscle weakness in early adulthood. Peripheral neuropathy is a universal feature in all cases. Various other neurological features such as spasticity, cerebellar signs and seizures, and involvement of other organ systems, including the heart, pancreas, and kidney may also be observed.
Intellectual disability v7.64 TRMT5 Arina Puzriakova Entity copied from Hereditary neuropathy or pain disorder v5.88
Intellectual disability v7.64 TRMT5 Arina Puzriakova gene: TRMT5 was added
gene: TRMT5 was added to Intellectual disability. Sources: Expert list,Expert Review Amber
Q3_24_promote_green, Q3_24_NHS_review tags were added to gene: TRMT5.
Mode of inheritance for gene: TRMT5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRMT5 were set to 35342985; 26189817; 29021354
Phenotypes for gene: TRMT5 were set to Peripheral neuropathy with variable spasticity, exercise intolerance, and developmental delay, OMIM:616539
Penetrance for gene: TRMT5 were set to Complete
Hereditary neuropathy or pain disorder v5.88 TRMT5 Arina Puzriakova Tag Q3_24_promote_green tag was added to TRMT5.
Tag Q3_24_NHS_review tag was added to TRMT5.
Hereditary neuropathy or pain disorder v5.87 TRMT5 Arina Puzriakova Publications for gene: TRMT5 were set to 35342985: 26189817: 29021354
Hereditary neuropathy or pain disorder v5.86 TRMT5 Arina Puzriakova Classified gene: TRMT5 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v5.86 TRMT5 Arina Puzriakova Added comment: Comment on list classification: New gene added to the panel by Alexander Rossor (UCL Institute of Neurology). There is sufficient evidence to promote this gene to Green at the next GMS panel update.

Associated with relevant phenotype in OMIM, but not associated with phenotype in G2P. At least 3 variants reported in at least three cases, together with supportive functional studies.

Phenotype is characterised as a highly variable multisystemic disorder, ranging from hypotonia and GDD in infancy to exercise intolerance and muscle weakness in early adulthood. Peripheral neuropathy is a universal feature in all cases. Various other neurological features such as spasticity, cerebellar signs and seizures, and involvement of other organ systems, including the heart, pancreas, and kidney may also be observed.
Hereditary neuropathy or pain disorder v5.86 TRMT5 Arina Puzriakova Gene: trmt5 has been classified as Amber List (Moderate Evidence).
Acute rhabdomyolysis v1.19 DMD Arina Puzriakova Phenotypes for gene: DMD were changed from Becker muscular dystrophy, OMIM:300376; Exercise induced crams and myoglobinuria to Becker muscular dystrophy, OMIM:300376; Exercise induced cramps and myoglobinuria
Likely inborn error of metabolism v6.21 TRMT5 Arina Puzriakova Phenotypes for gene: TRMT5 were changed from Combined oxidative phosphorylation deficiency 26 616539; Multiple Respiratory-Chain Deficiencies to Peripheral neuropathy with variable spasticity, exercise intolerance, and developmental delay, OMIM:616539
Mitochondrial disorders v7.6 TRMT5 Arina Puzriakova Phenotypes for gene: TRMT5 were changed from Combined oxidative phosphorylation deficiency 26 616539 to Peripheral neuropathy with variable spasticity, exercise intolerance, and developmental delay, OMIM:616539
Possible mitochondrial disorder - nuclear genes v3.108 TRMT5 Arina Puzriakova Phenotypes for gene: TRMT5 were changed from Combined oxidative phosphorylation deficiency 26, 616539 to Peripheral neuropathy with variable spasticity, exercise intolerance, and developmental delay, OMIM:616539
Hereditary neuropathy or pain disorder v5.85 TRMT5 Arina Puzriakova Phenotypes for gene: TRMT5 were changed from develomental delay; spasticity; peripheral neuropathy to Peripheral neuropathy with variable spasticity, exercise intolerance, and developmental delay, OMIM:616539
Hereditary neuropathy or pain disorder v5.84 UCHL1 Arina Puzriakova Publications for gene: UCHL1 were set to 35986737
Hereditary neuropathy or pain disorder v5.83 UCHL1 Arina Puzriakova Classified gene: UCHL1 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v5.83 UCHL1 Arina Puzriakova Added comment: Comment on list classification: Sensorimotor neuropathy has been reported in both Spastic paraplegia 79A, autosomal dominant, OMIM:620221 and Spastic paraplegia 79B, autosomal recessive, OMIM:615491. Sufficient unrelated cases for both MOIs to promote to Green at the next GMS panel update.
Hereditary neuropathy or pain disorder v5.83 UCHL1 Arina Puzriakova Gene: uchl1 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v5.82 UCHL1 Arina Puzriakova Tag Q3_24_promote_green tag was added to gene: UCHL1.
Tag Q3_24_NHS_review tag was added to gene: UCHL1.
Hereditary neuropathy or pain disorder v5.82 UCHL1 Arina Puzriakova Phenotypes for gene: UCHL1 were changed from spasticity; ataxia; peripheral neuropathy to Spastic paraplegia 79B, autosomal recessive, OMIM:615491; Spastic paraplegia 79A, autosomal dominant, OMIM:620221
Hereditary neuropathy or pain disorder v5.81 UQCRC1 Arina Puzriakova Classified gene: UQCRC1 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v5.81 UQCRC1 Arina Puzriakova Added comment: Comment on list classification: Rating Amber based on current evidence - three unrelated individuals with Parkinson's disease and heterozygous variants identified by one group (PMID: 33141179) but results have failed to be replicated in large European and Chinese cohorts (PMIDs: 33779694; 33248804).

This matches the latest classification on other GMS panels. Furthermore, polyneuropathy was only confirmed in 1/3 families. Knock-in mice with the affected family variant did exhibit significant reductions in distal CMAP amplitudes compared to WT littermates at 12 months (but not 9 months), as well as a slightly reduced conduction velocity but preserved distal motor latency. Peripheral nerve fibre morphology showed decrease in the diameter of myelinated nerve fibres.
Hereditary neuropathy or pain disorder v5.81 UQCRC1 Arina Puzriakova Gene: uqcrc1 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v5.80 UQCRC1 Arina Puzriakova Phenotypes for gene: UQCRC1 were changed from parkinsonism; peripheral neuropathy to Parkinsonism with polyneuropathy, OMIM:619279
Adult onset neurodegenerative disorder v6.7 VPS13D Arina Puzriakova Phenotypes for gene: VPS13D were changed from Spinocerebellar ataxia, autosomal recessive 4, 607317 to Spinocerebellar ataxia, autosomal recessive 4, OMIM:607317
Childhood onset dystonia, chorea or related movement disorder v5.7 VPS13D Arina Puzriakova Phenotypes for gene: VPS13D were changed from Spinocerebellar ataxia, autosomal recessive 4, 607317 to Spinocerebellar ataxia, autosomal recessive 4, OMIM:607317
Hereditary ataxia with onset in adulthood v6.8 VPS13D Arina Puzriakova Phenotypes for gene: VPS13D were changed from Autosomal recessive spinocerebellar ataxia 4, 608877; Spinocerebellar ataxia, autosomal recessive 4, 607317 to Spinocerebellar ataxia, autosomal recessive 4, OMIM:607317
Hereditary ataxia v1.333 VPS13D Arina Puzriakova Phenotypes for gene: VPS13D were changed from Spinocerebellar ataxia, autosomal recessive 4, 607317 to Spinocerebellar ataxia, autosomal recessive 4, OMIM:607317
Ataxia and cerebellar anomalies - narrow panel v6.6 VPS13D Arina Puzriakova Phenotypes for gene: VPS13D were changed from Spinocerebellar ataxia, autosomal recessive 4, 607317 to Spinocerebellar ataxia, autosomal recessive 4, OMIM:607317
Hereditary neuropathy or pain disorder v5.79 VPS13D Arina Puzriakova Phenotypes for gene: VPS13D were changed from ataxia; spasticity; peripheral neuropathy to Spinocerebellar ataxia, autosomal recessive 4, OMIM:607317
Hereditary neuropathy or pain disorder v5.78 VPS13D Arina Puzriakova Classified gene: VPS13D as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v5.78 VPS13D Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Alexander Rossor (UCL Institute of Neurology). There is sufficient evidence to promote this gene to Green at the next GMS panel update.

Biallelic variants in VPS13D cause a progressive spinocerebellar ataxia which can be associated with mild to moderate axonal sensorineural peripheral neuropathy. Sufficient unrelated cases to justify inclusion on the panel.
Hereditary neuropathy or pain disorder v5.78 VPS13D Arina Puzriakova Gene: vps13d has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v5.77 VPS13D Arina Puzriakova Tag Q3_24_promote_green tag was added to gene: VPS13D.
Tag Q3_24_NHS_review tag was added to gene: VPS13D.
Hereditary neuropathy or pain disorder v5.77 NUDT2 Achchuthan Shanmugasundram Tag watchlist was removed from gene: NUDT2.
Tag Q3_24_promote_green tag was added to gene: NUDT2.
Tag Q3_24_NHS_review tag was added to gene: NUDT2.
Hereditary neuropathy or pain disorder v5.77 NUDT2 Achchuthan Shanmugasundram Classified gene: NUDT2 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v5.77 NUDT2 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available now for the promotion of this gene to green rating in the next GMS update.
Hereditary neuropathy or pain disorder v5.77 NUDT2 Achchuthan Shanmugasundram Gene: nudt2 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v5.76 NUDT2 Achchuthan Shanmugasundram Phenotypes for gene: NUDT2 were changed from Sensorimotor polyneuropathy; Muscular hypotonia; Intellectual disability; no OMIM number to Intellectual developmental disorder with or without peripheral neuropathy, OMIM:619844
Hereditary neuropathy or pain disorder v5.75 NUDT2 Achchuthan Shanmugasundram Publications for gene: NUDT2 were set to 33058507
Hereditary neuropathy or pain disorder v5.74 NUDT2 Achchuthan Shanmugasundram edited their review of gene: NUDT2: Changed rating: GREEN
Hereditary neuropathy or pain disorder v5.74 NUDT2 Achchuthan Shanmugasundram edited their review of gene: NUDT2: Added comment: As reviewed by Alexander Rossor, PMID:38141063 reported 18 patients from 10 different families with a neurological disorder typified by intellectual disability, motor developmental delay and gait disturbance and they were all identified with biallelic NUDT2 variants. 71% of these patients had sensorimotor neuropathy.; Changed publications to: 27431290, 30059600, 33058507, 38141063
Hereditary neuropathy or pain disorder v5.74 NARS Achchuthan Shanmugasundram commented on gene: NARS: The new gene name for NARS is NARS1.
Hereditary neuropathy or pain disorder v5.74 NARS Achchuthan Shanmugasundram Tag new-gene-name tag was added to gene: NARS.
Hereditary neuropathy or pain disorder v5.74 NARS Achchuthan Shanmugasundram Classified gene: NARS as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v5.74 NARS Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the promotion of this gene top green rating on the next GMS update. The MOI can be set as 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal" as there are at least three cases reported with both modes of inheritance.
Hereditary neuropathy or pain disorder v5.74 NARS Achchuthan Shanmugasundram Gene: nars has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v5.73 NARS Achchuthan Shanmugasundram Phenotypes for gene: NARS were changed from developmental delay; seizures; peripheral neuropathy to Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, autosomal recessive, OMIM:619091; Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, autosomal dominant, OMIM:619092
Hereditary neuropathy or pain disorder v5.72 NARS Achchuthan Shanmugasundram changed review comment from: PMID:32738225 reported a total of 24 patients from 13 unrelated families with biallelic variants in the NARS1 gene and 8 unrelated patients with de novo heterozygous variants in the NARS1 gene. They presented with microcephaly, neurodevelopmental delay, seizures, peripheral neuropathy, and ataxia. Neuropathy was present in four patients from three families with biallelic variants and three unrelated individuals with monoallelic variants.

This gene has been associated with relevant phenotypes in both OMIM (MIMs #619091 & #619092) and Gene2Phenotype (monoallelic condition with 'strong' rating and biallelic condition with 'definitive' rating on the DD panel). This gene is also present with green rating on the 'Hereditary Neuropathy - complex' panel of PanelApp Australia.; to: PMID:32738225 reported a total of 24 patients from 13 unrelated families with biallelic variants in the NARS1 gene and 8 unrelated patients with de novo heterozygous variants in the NARS1 gene. They presented with microcephaly, neurodevelopmental delay, seizures, peripheral neuropathy, and ataxia. Neuropathy was present in four patients from three families with biallelic variants and three unrelated individuals with monoallelic variants. In addition, supportive functional data is also present.

This gene has been associated with relevant phenotypes in both OMIM (MIMs #619091 & #619092) and Gene2Phenotype (monoallelic condition with 'strong' rating and biallelic condition with 'definitive' rating on the DD panel). This gene is also present with green rating on the 'Hereditary Neuropathy - complex' panel of PanelApp Australia.
Hereditary neuropathy or pain disorder v5.72 NARS Achchuthan Shanmugasundram Publications for gene: NARS were set to 32738225:
Hereditary neuropathy or pain disorder v5.71 NARS Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: NARS.
Tag Q3_24_NHS_review tag was added to gene: NARS.
Hereditary neuropathy or pain disorder v5.71 NARS Achchuthan Shanmugasundram reviewed gene: NARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 32738225, 32788587; Phenotypes: Neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, autosomal recessive, OMIM:619091, Neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, autosomal dominant, OMIM:619092; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Limb disorders v6.2 COL5A1 Tracy Lester gene: COL5A1 was added
gene: COL5A1 was added to Limb disorders. Sources: NHS GMS
Mode of inheritance for gene: COL5A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL5A1 were set to 21611149; 20847697
Phenotypes for gene: COL5A1 were set to EDS
Penetrance for gene: COL5A1 were set to Complete
Review for gene: COL5A1 was set to GREEN
Added comment: I am not sure if the right panel to add this gene but it should be included in R27 due to severe EDS presenting in childhood - this also applies to COL5A2. We have reported a possible fetal case of EDS with multiple joint flexions on scan and a nonsense variant in COL5A1
Sources: NHS GMS
Monogenic hearing loss v4.57 RFC4 Achchuthan Shanmugasundram Classified gene: RFC4 as Amber List (moderate evidence)
Monogenic hearing loss v4.57 RFC4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of this gene with sensorineural hearing impairment. Hence, this gene should be promoted to green rating in the next GMS update.
Monogenic hearing loss v4.57 RFC4 Achchuthan Shanmugasundram Gene: rfc4 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v4.56 RFC4 Achchuthan Shanmugasundram gene: RFC4 was added
gene: RFC4 was added to Monogenic hearing loss. Sources: Literature
Q3_24_promote_green tags were added to gene: RFC4.
Mode of inheritance for gene: RFC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RFC4 were set to 39106866
Phenotypes for gene: RFC4 were set to sensorineural hearing loss disorder, MONDO:0020678
Review for gene: RFC4 was set to GREEN
Added comment: PMID:39106866 reported nine individuals (aged birth to 47 years) from eight unrelated families with a multisystem disorder.

They presented with muscle weakness/myopathy (9/9), motor incoordination/gait disturbance (8/8), delayed gross motor development (6/9), dysarthria (5/5), peripheral neuropathy (3/3 adults), bilateral sensorineural hearing impairment (6/9), decreased body weight (8/9), short stature (5/9), microcephaly (4/9), respiratory issues/insufficiency (6/9), cerebellar atrophy (4/9), pituitary hypoplasia (3/9).

They were identified with biallelic loss-of-function variants in RFC4 gene (3 frameshift, 2 splice site, 1 single AA duplication, 2 single AA deletions and 2 missense)

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Congenital myopathy v4.44 RFC4 Achchuthan Shanmugasundram Classified gene: RFC4 as Amber List (moderate evidence)
Congenital myopathy v4.44 RFC4 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of this gene with congenital myopathy. Hence, this gene should be promoted to green rating in the next GMS update.
Congenital myopathy v4.44 RFC4 Achchuthan Shanmugasundram Gene: rfc4 has been classified as Amber List (Moderate Evidence).
Congenital myopathy v4.43 RFC4 Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: RFC4.
Congenital myopathy v4.43 RFC4 Achchuthan Shanmugasundram gene: RFC4 was added
gene: RFC4 was added to Congenital myopathy. Sources: Literature
Mode of inheritance for gene: RFC4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RFC4 were set to 39106866
Phenotypes for gene: RFC4 were set to congenital myopathy, MONDO:0019952
Review for gene: RFC4 was set to GREEN
Added comment: PMID:39106866 reported nine individuals (aged birth to 47 years) from eight unrelated families with a multisystem disorder.

They presented with muscle weakness/myopathy (9/9), motor incoordination/gait disturbance (8/8), delayed gross motor development (6/9), dysarthria (5/5), peripheral neuropathy (3/3 adults), bilateral sensorineural hearing impairment (6/9), decreased body weight (8/9), short stature (5/9), microcephaly (4/9), respiratory issues/insufficiency (6/9), cerebellar atrophy (4/9), pituitary hypoplasia (3/9).

The age of onset of eight of nine individuals ranged from neonatal to childhood, while one individual had onset of symptoms in mid-30s.

They were identified with biallelic loss-of-function variants in RFC4 gene (3 frameshift, 2 splice site, 1 single AA duplication, 2 single AA deletions and 2 missense)

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature
Hereditary neuropathy or pain disorder v5.71 FICD Achchuthan Shanmugasundram Classified gene: FICD as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v5.71 FICD Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (three unrelated families with the same homozygous variant and functional studies) for the association of this gene with green rating in the next GMS update.
Hereditary neuropathy or pain disorder v5.71 FICD Achchuthan Shanmugasundram Gene: ficd has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v5.70 FICD Achchuthan Shanmugasundram gene: FICD was added
gene: FICD was added to Hereditary neuropathy or pain disorder. Sources: Literature
Q3_24_promote_green tags were added to gene: FICD.
Mode of inheritance for gene: FICD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FICD were set to 36136088
Phenotypes for gene: FICD were set to Spastic paraplegia 92, autosomal recessive, OMIM:620911
Review for gene: FICD was set to GREEN
Added comment: PMID:36136088 reported three unrelated families with recurrent homozygous missense variant in FICD gene (p.Arg374His) and the patients presented with a a neurodegenerative disease of upper and lower motor neurons. A patient from one further family was identified with compound heterozygous variants in FICD gene (p.Arg374His and p.Gly370GlufsTer53).

All these patients had onset of symptoms in childhood with progressive course. Their clinical manifestations included severe lower limb spasticity and mild upper limb spasticity. In addition, nerve conduction test showed motor neuropathy in the four patients with homozygous p.Arg374His variant, whereas this test was not done in the patient with compound heterozygous variants.

Fibroblasts from patients with FICD variants have abnormally increased levels of AMPylated and thus inactivated BiP.

This gene has been associated with relevant phenotypes in OMIM (MIM #620911).
Sources: Literature
Childhood onset hereditary spastic paraplegia v6.9 FICD Achchuthan Shanmugasundram Classified gene: FICD as Amber List (moderate evidence)
Childhood onset hereditary spastic paraplegia v6.9 FICD Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (four unrelated families and functional work) for the association of this gene with green rating on the next GMS update.
Childhood onset hereditary spastic paraplegia v6.9 FICD Achchuthan Shanmugasundram Gene: ficd has been classified as Amber List (Moderate Evidence).
Childhood onset hereditary spastic paraplegia v6.8 FICD Achchuthan Shanmugasundram gene: FICD was added
gene: FICD was added to Childhood onset hereditary spastic paraplegia. Sources: Literature
Q3_24_promote_green tags were added to gene: FICD.
Mode of inheritance for gene: FICD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FICD were set to 36136088
Phenotypes for gene: FICD were set to Spastic paraplegia 92, autosomal recessive, OMIM:620911
Review for gene: FICD was set to GREEN
Added comment: PMID:36136088 reported three unrelated families with recurrent homozygous missense variant in FICD gene (p.Arg374His) and the patients presented with a a neurodegenerative disease of upper and lower motor neurons. A patient from one further family was identified with compound heterozygous variants in FICD gene (p.Arg374His and p.Gly370GlufsTer53).

All these patients had onset of symptoms in childhood with progressive course. Their clinical manifestations included severe lower limb spasticity and mild upper limb spasticity. In addition, nerve conduction test showed motor neuropathy.

Fibroblasts from patients with FICD variants have abnormally increased levels of AMPylated and thus inactivated BiP.

This gene has been associated with relevant phenotypes in OMIM (MIM #620911).
Sources: Literature
Ataxia and cerebellar anomalies - narrow panel v6.5 FDXR Arina Puzriakova Classified gene: FDXR as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v6.5 FDXR Arina Puzriakova Gene: fdxr has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v6.4 FDXR Arina Puzriakova gene: FDXR was added
gene: FDXR was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Q3_24_promote_green tags were added to gene: FDXR.
Mode of inheritance for gene: FDXR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FDXR were set to 37046037
Phenotypes for gene: FDXR were set to Multiple mitochondrial dysfunctions syndrome 9B, OMIM:620887
Review for gene: FDXR was set to GREEN
Added comment: There is sufficient evidence to promote this gene to Green at the next GMS panel update.

Review by Masnada et al (2023) of 44 individuals from 35 families reported in literature with FDXR variants revealed ataxia in more than 40% of patients. More complex cases also showed cerebellar atrophy/hypoplasia on neuroimaging (13.63%). In most cases neurological signs developed with progression of disease but presentation since clinical onset has also been described. Most common features include optic neuropathy (93.2%) and acoustic neuropathy (50%).
Sources: Literature
Mitochondrial disorders v7.5 FDXR Arina Puzriakova Phenotypes for gene: FDXR were changed from Auditory neuropathy and optic atrophy 617717 to Auditory neuropathy and optic atrophy, OMIM:617717; Multiple mitochondrial dysfunctions syndrome 9B, OMIM:620887
Likely inborn error of metabolism v6.20 FDXR Arina Puzriakova Phenotypes for gene: FDXR were changed from Auditory neuropathy and optic atrophy 617717 to Auditory neuropathy and optic atrophy, OMIM:617717; Multiple mitochondrial dysfunctions syndrome 9B, OMIM:620887
Possible mitochondrial disorder - nuclear genes v3.107 FDXR Arina Puzriakova Phenotypes for gene: FDXR were changed from Auditory neuropathy and optic atrophy, 617717 to Auditory neuropathy and optic atrophy, OMIM:617717; Multiple mitochondrial dysfunctions syndrome 9B, OMIM:620887
Monogenic hearing loss v4.55 FDXR Arina Puzriakova Phenotypes for gene: FDXR were changed from Auditory neuropathy and optic atrophy, OMIM:617717 to Auditory neuropathy and optic atrophy, OMIM:617717; Multiple mitochondrial dysfunctions syndrome 9B, OMIM:620887
Optic neuropathy v4.34 FDXR Arina Puzriakova Phenotypes for gene: FDXR were changed from Auditory neuropathy and optic atrophy, 617717 to Auditory neuropathy and optic atrophy, OMIM:617717; Multiple mitochondrial dysfunctions syndrome 9B, OMIM:620887
Hereditary neuropathy or pain disorder v5.69 FDXR Arina Puzriakova Tag Q3_24_promote_green tag was added to gene: FDXR.
Tag Q3_24_NHS_review tag was added to gene: FDXR.
Hereditary neuropathy or pain disorder v5.69 FDXR Arina Puzriakova Classified gene: FDXR as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v5.69 FDXR Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Alexander Rossor (UCL Institute of Neurology). There is sufficient evidence to promote this gene to Green at the next GMS panel update.

Review by Masnada et al (2023) of 44 individuals from 35 families reported in literature with FDXR variants revealed sensorimotor peripheral polyneuropathy in more than 20% of patients. In most cases peripheral neuropathy manifests in late stages of disease but presentation since clinical onset has also been described. Other common features include optic neuropathy (93.2%) and acoustic neuropathy (50%).
Hereditary neuropathy or pain disorder v5.69 FDXR Arina Puzriakova Gene: fdxr has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v5.68 FDXR Arina Puzriakova Publications for gene: FDXR were set to 37046037: 30250212 :
Hereditary neuropathy or pain disorder v5.67 FDXR Arina Puzriakova Phenotypes for gene: FDXR were changed from optic neuropathy; auditory neuropathy; peripheral neuropathy to Multiple mitochondrial dysfunctions syndrome 9B, OMIM:620887
Skeletal dysplasia v6.27 EXOC6B Achchuthan Shanmugasundram Deleted their comment
Skeletal dysplasia v6.27 EXOC6B Achchuthan Shanmugasundram Classified gene: EXOC6B as Amber List (moderate evidence)
Skeletal dysplasia v6.27 EXOC6B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (four unrelated cases and functional evidence) for the association of this gene with green rating on the next GMS update.
Skeletal dysplasia v6.27 EXOC6B Achchuthan Shanmugasundram Gene: exoc6b has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v6.27 EXOC6B Achchuthan Shanmugasundram Classified gene: EXOC6B as Amber List (moderate evidence)
Skeletal dysplasia v6.27 EXOC6B Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available (four unrelated cases and functional evidence) for the association of this gene with green rating on the next GMS update.
Skeletal dysplasia v6.27 EXOC6B Achchuthan Shanmugasundram Gene: exoc6b has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v6.26 EXOC6B Achchuthan Shanmugasundram gene: EXOC6B was added
gene: EXOC6B was added to Skeletal dysplasia. Sources: Literature
Q3_24_promote_green tags were added to gene: EXOC6B.
Mode of inheritance for gene: EXOC6B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOC6B were set to 26669664; 30284759; 36150098
Phenotypes for gene: EXOC6B were set to Spondyloepimetaphyseal dysplasia with joint laxity, type 3, OMIM:618395
Review for gene: EXOC6B was set to GREEN
Added comment: PMID:26669664 reported two brothers with spondyloepimetaphyseal dysplasia (SEMD), multiple joint dislocations at birth, severe joint laxity, scoliosis, gracile metacarpals and metatarsals, delayed bone age and poorly ossified carpal and tarsal bones. They were identified with a homozygous nonsense variant in EXOC6B gene (p.Tyr302Ter).

PMID:30284759 reported two sisters with dislocations of the hips and knees, long slender fingers with distal tapering and significant motor disability but normal (older sister) or low-normal intelligence (younger sister). They were identified with a homozygous in-frame deletion of exons 9-20 in EXOC6B gene.

PMID:36150098 reported two unrelated individuals with the same condition, Spondyloepimetaphyseal dysplasia with joint laxity, type 3. One of them was identified with a homozygous frameshift exon 20 deletion and the other with a homozygous nonsense variant (p.Leu134Ter). Functional studies on patient fibroblast cell lines indicated abrogation of exocytosis leading to impaired primary ciliogenesis.

This gene has been associated with relevant phenotypes in OMIM (MIM #618395), but not yet in Gene2Phenotype.
Sources: Literature
Hereditary neuropathy or pain disorder v5.66 EMILIN1 Arina Puzriakova changed review comment from: Comment on list classification: This is now sufficient evidence to promote this gene to Green at the next GMS panel update. At least three unrelated families reported with heterozygous variant in the EMILIN1 gene and neuropathy.

The third family includes a proband with childhood-onset sensory-motor neuropathy and pyramidal signs (ataxic-spastic gait). Sequencing revealed two heterozygous missense variants, c.544G>A and c.546G>C, which authors renamed as c.544_546GAG>AAC (p.E182N) as the variants were in cis and located at the same protein residue. The proband's mother, carrying the same variant, presented with a milder peripheral nerve disorder, hypermobility of joints and ligamentous laxity, and moderate inflammatory arthropathy.; to: Comment on list classification: This is now sufficient evidence to promote this gene to Green at the next GMS panel update. At least three unrelated families reported with heterozygous variant in the EMILIN1 gene and neuropathy.

The third family (PMID:38963291) includes a proband with childhood-onset sensory-motor neuropathy and pyramidal signs (ataxic-spastic gait). Sequencing revealed two heterozygous missense variants, c.544G>A and c.546G>C, which authors renamed as c.544_546GAG>AAC (p.E182N) as the variants were in cis and located at the same protein residue. The proband's mother, carrying the same variant, presented with a milder peripheral nerve disorder, hypermobility of joints and ligamentous laxity, and moderate inflammatory arthropathy.
Hereditary neuropathy or pain disorder v5.66 EMILIN1 Arina Puzriakova Classified gene: EMILIN1 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v5.66 EMILIN1 Arina Puzriakova Added comment: Comment on list classification: This is now sufficient evidence to promote this gene to Green at the next GMS panel update. At least three unrelated families reported with heterozygous variant in the EMILIN1 gene and neuropathy.

The third family includes a proband with childhood-onset sensory-motor neuropathy and pyramidal signs (ataxic-spastic gait). Sequencing revealed two heterozygous missense variants, c.544G>A and c.546G>C, which authors renamed as c.544_546GAG>AAC (p.E182N) as the variants were in cis and located at the same protein residue. The proband's mother, carrying the same variant, presented with a milder peripheral nerve disorder, hypermobility of joints and ligamentous laxity, and moderate inflammatory arthropathy.
Hereditary neuropathy or pain disorder v5.66 EMILIN1 Arina Puzriakova Gene: emilin1 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v5.65 EMILIN1 Arina Puzriakova Publications for gene: EMILIN1 were set to 31978608; 26462740
Hereditary neuropathy or pain disorder v5.64 EMILIN1 Arina Puzriakova Tag Q3_24_promote_green tag was added to gene: EMILIN1.
Tag Q3_24_NHS_review tag was added to gene: EMILIN1.
Skeletal dysplasia v6.25 BGN Achchuthan Shanmugasundram Classified gene: BGN as Amber List (moderate evidence)
Skeletal dysplasia v6.25 BGN Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of this gene with green rating on the next GMS update.
Skeletal dysplasia v6.25 BGN Achchuthan Shanmugasundram Gene: bgn has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v6.24 BGN Achchuthan Shanmugasundram Phenotypes for gene: BGN were changed from Skeletal dysplasia; Spondyloepimetaphyseal dysplasia to Spondyloepimetaphyseal dysplasia, X-linked, OMIM:300106
Skeletal dysplasia v6.24 BGN Achchuthan Shanmugasundram Mode of inheritance for gene: BGN was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Skeletal dysplasia v6.23 BGN Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: BGN.
Tag Q3_24_NHS_review tag was added to gene: BGN.
Skeletal dysplasia v6.23 BGN Achchuthan Shanmugasundram reviewed gene: BGN: Rating: GREEN; Mode of pathogenicity: None; Publications: 27236923; Phenotypes: Spondyloepimetaphyseal dysplasia, X-linked, OMIM:300106; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability v7.63 DDX17 Achchuthan Shanmugasundram Classified gene: DDX17 as Amber List (moderate evidence)
Intellectual disability v7.63 DDX17 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of this gene with green rating in the next GMS update.
Intellectual disability v7.63 DDX17 Achchuthan Shanmugasundram Gene: ddx17 has been classified as Amber List (Moderate Evidence).
Intellectual disability v7.62 DDX17 Achchuthan Shanmugasundram Phenotypes for gene: DDX17 were changed from Intellectual disability; delayed speech and language; motor delay to neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v7.62 DDX17 Achchuthan Shanmugasundram Publications for gene: DDX17 were set to PMID: 39405200
Intellectual disability v7.61 DDX17 Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: DDX17.
Tag Q3_24_NHS_review tag was added to gene: DDX17.
Intellectual disability v7.61 DDX17 Achchuthan Shanmugasundram reviewed gene: DDX17: Rating: GREEN; Mode of pathogenicity: None; Publications: 39405200; Phenotypes: neurodevelopmental disorder, MONDO:0700092, intellectual disability, MONDO:0001071; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v6.14 AJAP1 Achchuthan Shanmugasundram Deleted their comment
Early onset or syndromic epilepsy v6.14 AJAP1 Achchuthan Shanmugasundram Classified gene: AJAP1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v6.14 AJAP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of this gene with green rating in the next GMS update.
Early onset or syndromic epilepsy v6.14 AJAP1 Achchuthan Shanmugasundram Gene: ajap1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v6.14 AJAP1 Achchuthan Shanmugasundram Deleted their comment
Early onset or syndromic epilepsy v6.14 AJAP1 Achchuthan Shanmugasundram Classified gene: AJAP1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v6.14 AJAP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of this gene with green rating in the next GMS update.
Early onset or syndromic epilepsy v6.14 AJAP1 Achchuthan Shanmugasundram Gene: ajap1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v6.14 AJAP1 Achchuthan Shanmugasundram Classified gene: AJAP1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v6.14 AJAP1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence available for the association of this gene with green rating in the next GMS update.
Early onset or syndromic epilepsy v6.14 AJAP1 Achchuthan Shanmugasundram Gene: ajap1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v6.13 AJAP1 Achchuthan Shanmugasundram Phenotypes for gene: AJAP1 were changed from Epileptic seizures; developmental disorder; intellectual disability to neurodevelopmental disorder, MONDO:0700092; epilepsy, MONDO:0005027
Early onset or syndromic epilepsy v6.12 AJAP1 Achchuthan Shanmugasundram Publications for gene: AJAP1 were set to 38985877
Early onset or syndromic epilepsy v6.12 AJAP1 Achchuthan Shanmugasundram Publications for gene: AJAP1 were set to PMID: 38985877
Early onset or syndromic epilepsy v6.11 AJAP1 Achchuthan Shanmugasundram Tag Q3_24_promote_green tag was added to gene: AJAP1.
Tag Q3_24_NHS_review tag was added to gene: AJAP1.
Early onset or syndromic epilepsy v6.11 AJAP1 Achchuthan Shanmugasundram edited their review of gene: AJAP1: Changed phenotypes to: neurodevelopmental disorder, MONDO:0700092, epilepsy, MONDO:0005027
Early onset or syndromic epilepsy v6.11 AJAP1 Achchuthan Shanmugasundram changed review comment from: As reviewed by Hannah Knight, there are five unrelated individuals reported with monoallelic variants or a deletion in AJAP1 gene, of which four patients presented with epilepsy.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.; to: As reviewed by Hannah Knight, PMID:38985877 reported five unrelated individuals with monoallelic variants or a deletion in AJAP1 gene, of which four patients presented with epilepsy.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Early onset or syndromic epilepsy v6.11 AJAP1 Achchuthan Shanmugasundram reviewed gene: AJAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 38985877; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v5.64 AP5Z1 Sarah Leigh Phenotypes for gene: AP5Z1 were changed from spasticity; ataxia; retinopathy; neuropathy; parkinsonism to Spastic paraplegia 48, autosomal recessive, OMIM:613647; hereditary spastic paraplegia 48, MONDO:0013342
Hereditary neuropathy or pain disorder v5.63 AP5Z1 Sarah Leigh Classified gene: AP5Z1 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v5.63 AP5Z1 Sarah Leigh Gene: ap5z1 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v5.62 AMPD2 Sarah Leigh reviewed gene: AMPD2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary neuropathy or pain disorder v5.62 AMPD2 Sarah Leigh Phenotypes for gene: AMPD2 were changed from pontocerebellar hypoplasia, axonal neuropathy, to Pontocerebellar hypoplasia, type 9, OMIM:615809; pontocerebellar hypoplasia type 9, MONDO:0014351
Hereditary neuropathy or pain disorder v5.61 AMPD2 Sarah Leigh Classified gene: AMPD2 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v5.61 AMPD2 Sarah Leigh Gene: ampd2 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v5.60 AMACR Sarah Leigh Tag Q3_24_promote_green tag was added to gene: AMACR.
Tag Q3_24_NHS_review tag was added to gene: AMACR.
Hereditary neuropathy or pain disorder v5.60 AMACR Sarah Leigh reviewed gene: AMACR: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary neuropathy or pain disorder v5.60 AMACR Sarah Leigh Publications for gene: AMACR were set to 21576695; 10655068; 20821052; 18032455
Hereditary neuropathy or pain disorder v5.59 AMACR Sarah Leigh Phenotypes for gene: AMACR were changed from cerebellar ataxia; peripheral neuropathy; seizures; cataracts; retinitis pigmentosa to Alpha-methylacyl-CoA racemase deficiency, OMIM:614307; alpha-methylacyl-CoA racemase deficiency, MONDO:0013681
Hereditary neuropathy or pain disorder v5.58 AMACR Sarah Leigh Classified gene: AMACR as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v5.58 AMACR Sarah Leigh Gene: amacr has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v5.57 ALDH18A1 Sarah Leigh reviewed gene: ALDH18A1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary neuropathy or pain disorder v5.57 ALDH18A1 Sarah Leigh Classified gene: ALDH18A1 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v5.57 ALDH18A1 Sarah Leigh Gene: aldh18a1 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v5.56 ALDH18A1 Sarah Leigh Phenotypes for gene: ALDH18A1 were changed from spastic paraplegia; cognitive impairment; motor neuronopathy to Spastic paraplegia 9A, autosomal dominant, OMIM:601162; hereditary spastic paraplegia 9A, MONDO:0011006; Spastic paraplegia 9B, autosomal recessive, OMIM:616586; autosomal recessive complex spastic paraplegia type 9B, MONDO:0014702
Hereditary neuropathy or pain disorder v5.55 ALDH18A1 Sarah Leigh Publications for gene: ALDH18A1 were set to https://doi.org/10.1093/brain/awv143
Hereditary neuropathy or pain disorder v5.54 AFG3L2 Sarah Leigh reviewed gene: AFG3L2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary neuropathy or pain disorder v5.54 AFG3L2 Sarah Leigh Phenotypes for gene: AFG3L2 were changed from Optic atrophy 12,OMIM; 618977; Spastic ataxia 5, autosomal recessive, OMIM:614487 to Spastic ataxia 5, autosomal recessive, OMIM:614487
Hereditary neuropathy or pain disorder v5.53 AFG3L2 Sarah Leigh Phenotypes for gene: AFG3L2 were changed from spasticity, peripheral neuropathy, ptosis, oculomotor apraxia; dystonia; cerebellar atrophy; progressive myoclonic epilepsy to Optic atrophy 12,OMIM; 618977; Spastic ataxia 5, autosomal recessive, OMIM:614487
Hereditary neuropathy or pain disorder v5.52 AFG3L2 Sarah Leigh Publications for gene: AFG3L2 were set to 22022284:
Hereditary neuropathy or pain disorder v5.51 AFG3L2 Sarah Leigh Classified gene: AFG3L2 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v5.51 AFG3L2 Sarah Leigh Gene: afg3l2 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v5.50 ADPRHL2 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: ADPRHL2.
Tag Q3_24_NHS_review tag was added to gene: ADPRHL2.
Hereditary neuropathy or pain disorder v5.50 ADPRHL2 Sarah Leigh reviewed gene: ADPRHL2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary neuropathy or pain disorder v5.50 ADPRHL2 Sarah Leigh Phenotypes for gene: ADPRHL2 were changed from Neurodegeneration; childhood-onset; ataxia; seizure; axonal polyneuropathy to Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, OMIM:618170; neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, MONDO:0100095
Hereditary neuropathy or pain disorder v5.49 ADPRHL2 Sarah Leigh Publications for gene: ADPRHL2 were set to 30401461: 30100084
Hereditary neuropathy or pain disorder v5.48 ADPRHL2 Sarah Leigh Classified gene: ADPRHL2 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v5.48 ADPRHL2 Sarah Leigh Gene: adprhl2 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v5.47 ADGRG6 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: ADGRG6.
Tag Q3_24_NHS_review tag was added to gene: ADGRG6.
Hereditary neuropathy or pain disorder v5.47 ADGRG6 Sarah Leigh reviewed gene: ADGRG6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary neuropathy or pain disorder v5.47 ADGRG6 Sarah Leigh Phenotypes for gene: ADGRG6 were changed from Lethal congenital contracture syndrome 9, OMIM:616503 to Lethal congenital contracture syndrome 9, OMIM:616503; lethal congenital contracture syndrome 9, MONDO:0014670
Hereditary neuropathy or pain disorder v5.46 ADGRG6 Sarah Leigh Phenotypes for gene: ADGRG6 were changed from lethal congenital contracture syndrome; lack of peripheral myelination to Lethal congenital contracture syndrome 9, OMIM:616503
Hereditary neuropathy or pain disorder v5.45 ADGRG6 Sarah Leigh Classified gene: ADGRG6 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v5.45 ADGRG6 Sarah Leigh Gene: adgrg6 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v5.44 ADCY6 Sarah Leigh Tag Q3_24_promote_green tag was added to gene: ADCY6.
Tag Q3_24_NHS_review tag was added to gene: ADCY6.
Hereditary neuropathy or pain disorder v5.44 ADCY6 Sarah Leigh reviewed gene: ADCY6: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hereditary neuropathy or pain disorder v5.44 ADCY6 Sarah Leigh Publications for gene: ADCY6 were set to 31846058: 26257172: 24319099
Hereditary neuropathy or pain disorder v5.43 ADCY6 Sarah Leigh Phenotypes for gene: ADCY6 were changed from Lethal congenital contracture syndrome 8, OMIM:616287 to Lethal congenital contracture syndrome 8, OMIM:616287; lethal congenital contracture syndrome 8, MONDO:0014570
Hereditary neuropathy or pain disorder v5.42 ADCY6 Sarah Leigh Phenotypes for gene: ADCY6 were changed from lethal congenital contracture syndrome; loss of axons to Lethal congenital contracture syndrome 8, OMIM:616287
Hereditary neuropathy or pain disorder v5.41 ADCY6 Sarah Leigh Classified gene: ADCY6 as Amber List (moderate evidence)