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Intellectual disability v9.355 BRF2 Ida Ertmanska changed review comment from: PMID: 40229899 Mattioli et al., 2025
Report of six families (3 Icelandic, 1 Iranian, 1 Pakistani, 1 of unknown ancestry) with bi-allelic variants in BRF2 presenting with early mortality, brain, and craniofacial anomalies and/or neurodevelopmental disorders (NDD). Patients had phenotypes ranging from perinatal death to Treacher-Collins and craniosynostosis with radial defects and immunodeficiency or global developmental delay, hearing, and vision impairment.
Families 1-3 = Icelandic families with founder BRF2 variant c.214 + 1G > A, not much detail provided on phenotype beyond "early lethality". Genotyping was not done for the affected fetuses, it was inferred from living family members.

Family 4 - female proband with Treacher-Collins syndrome, presented with hearing impairment, soft cleft palate, microcephaly, and facial dysmorphism. She was homozygous for BRF2 c.481G > T; p.(Gly161*).

Family 5 - 2 sibs compound het for BRF2 c.782C > T ; p.(Pro261Leu) & c.404_409delinsA; p.(Met135Asnfs*15);
Patient II:1 female, presented with coronal synostosis, microcephaly, hypertelorism, a small beaked, nose, retrognathia, shortened right radius, and absent left radius, with radial deviation of the hands and contractures of all fingers. She was found to have anemia, leukocytosis, marked eosinophilia, and thrombocytopenia, and developed a significant rash by 1 month of age; she died at 2 mo from bacterial infection.
Patient II:2, male - presented with frontal bone hypoplasia with bilateral coronal synostosis, micrognathia, small orbits, low-set ears, downward slanting palpebral fissures, and significantly decreased B-cell CD19 subsets. He subsequently developed ichthyosiform erythroderma and eosinophilic myeloid hyperplasia. He had developmental and speech delays.

Family 6 - 4 affected sibs with moderate ID, and delays in motor and speech development; 2 sibs had mild hearing and vision impairment. 2 sibs confirmed homozygous for BRF2 c.31G > A; p.(Gly11Ser).

Zebrafish knocked down for the orthologous brf2 presented with abnormal escape response, reduced swimming velocity and head size, and craniofacial malformations. Phenotype was rescued by human BRF2, but not by isoforms with patients variants.

PMID: 40781771 Yoon et al., 2025
Case report of a girl, presumed Korean born to non-consanguineous parents, with multiple congenital anomalies: polydactyly of the right fifth toe, duplex kidney on the right side, hypodontia, and dysmorphic facial features. She had recurrent infections in the neonatal period, and was diagnosed with primary immunodeficiency at 4 months. Mild ID (IQ=60) was diagnosed at age 16 yrs. She harboured comp het BRF2 variants: c.379C>T, p.Arg127Ter & c.782C>T, p.Pro261Leu. Older sister was similarly affected; she died of infection at 19 months.
Single-cell RNA-seq analysis of the patient sample revealed transcriptional abnormalities in PBMCs from the patient harboring BRF2 mutations. BRF2 mutations disrupt RNA Pol III activity specifically at type III promoters, leading to transcriptional dysregulation of critical noncoding RNAs

BRF2 is not yet associated with a phenotype in OMIM (accessed 27 Mar 2026).
Sources: Literature
Sources: Literature; to: PMID: 40229899 Mattioli et al., 2025
Report of six families (3 Icelandic, 1 Iranian, 1 Pakistani, 1 of unknown ancestry) with bi-allelic variants in BRF2 presenting with early mortality, brain, and craniofacial anomalies and/or neurodevelopmental disorders (NDD). Patients had phenotypes ranging from perinatal death to Treacher-Collins and craniosynostosis with radial defects and immunodeficiency or global developmental delay, hearing, and vision impairment.
Families 1-3 = Icelandic families with founder BRF2 variant c.214 + 1G > A, not much detail provided on phenotype beyond "early lethality". Genotyping was not done for the affected fetuses, it was inferred from living family members.

Family 4 - female proband with Treacher-Collins syndrome, presented with hearing impairment, soft cleft palate, microcephaly, and facial dysmorphism. She was homozygous for BRF2 c.481G > T; p.(Gly161*).

Family 5 - 2 sibs compound het for BRF2 c.782C > T ; p.(Pro261Leu) & c.404_409delinsA; p.(Met135Asnfs*15);
Patient II:1 female, presented with coronal synostosis, microcephaly, hypertelorism, a small beaked, nose, retrognathia, shortened right radius, and absent left radius, with radial deviation of the hands and contractures of all fingers. She was found to have anemia, leukocytosis, marked eosinophilia, and thrombocytopenia, and developed a significant rash by 1 month of age; she died at 2 mo from bacterial infection.
Patient II:2, male - presented with frontal bone hypoplasia with bilateral coronal synostosis, micrognathia, small orbits, low-set ears, downward slanting palpebral fissures, and significantly decreased B-cell CD19 subsets. He subsequently developed ichthyosiform erythroderma and eosinophilic myeloid hyperplasia. He had developmental and speech delays.

Family 6 - 4 affected sibs with moderate ID, and delays in motor and speech development; 2 sibs had mild hearing and vision impairment. 2 sibs confirmed homozygous for BRF2 c.31G > A; p.(Gly11Ser).

Zebrafish knocked down for the orthologous brf2 presented with abnormal escape response, reduced swimming velocity and head size, and craniofacial malformations. Phenotype was rescued by human BRF2, but not by isoforms with patients variants.

PMID: 40781771 Yoon et al., 2025
Case report of a girl, presumed Korean born to non-consanguineous parents, with multiple congenital anomalies: polydactyly of the right fifth toe, duplex kidney on the right side, hypodontia, and dysmorphic facial features. She had recurrent infections in the neonatal period, and was diagnosed with primary immunodeficiency at 4 months. Mild ID (IQ=60) was diagnosed at age 16 yrs. She harboured comp het BRF2 variants: c.379C>T, p.Arg127Ter & c.782C>T, p.Pro261Leu. Older sister was similarly affected; she died of infection at 19 months.
Single-cell RNA-seq analysis of the patient sample revealed transcriptional abnormalities in PBMCs from the patient harboring BRF2 mutations. BRF2 mutations disrupt RNA Pol III activity specifically at type III promoters, leading to transcriptional dysregulation of critical noncoding RNAs

BRF2 is not yet associated with a phenotype in OMIM (accessed 27 Mar 2026).
Sources: Literature
Paediatric disorders - additional genes v7.41 BRF2 Ida Ertmanska changed review comment from: Comment on list classification: There are at least 4 unrelated families with biallelic BRF2 variants and multiple congenital anomalies (+ multiple Icelandic families with a founder splice variant). The findings are not consistent and include facial dysmorphism, immunodeficiency, ID, skin rashes, contractures, polydactyly, and more. The gene has been tagged for promotion on Intellectual disability, which ensures inclusion on R27. Hence, added a curated_removed tag.; to: Comment on list classification: There are at least 4 unrelated families with biallelic BRF2 variants and multiple congenital anomalies (+ multiple Icelandic families with a founder splice variant). The findings are not consistent and include facial dysmorphism, immunodeficiency, ID, skin rashes, contractures, polydactyly, and more. The gene has been tagged for promotion to Green on Intellectual disability, which ensures inclusion on R27. Hence, added a curated_removed tag and rated Grey on this panel.
Paediatric disorders - additional genes v7.41 BRF2 Ida Ertmanska reviewed gene: BRF2: Rating: ; Mode of pathogenicity: None; Publications: 40229899, 40781771; Phenotypes: multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042, intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric disorders - additional genes v7.41 BRF2 Ida Ertmanska Deleted their review
Paediatric disorders - additional genes v7.41 BRF2 Ida Ertmanska Deleted their comment
Paediatric disorders - additional genes v7.41 BRF2 Ida Ertmanska Deleted their comment
Intellectual disability v9.355 BRF2 Ida Ertmanska Classified gene: BRF2 as Amber List (moderate evidence)
Intellectual disability v9.355 BRF2 Ida Ertmanska Added comment: Comment on list classification: There are 3 unrelated families with biallelic BRF2 variants and syndromic congenital anomalies, including intellectual disability and developmental delay. Hence, this gene can be promoted to Green at the next udpate, which also ensures inclusion on R27 Paediatric disorders.
Intellectual disability v9.355 BRF2 Ida Ertmanska Gene: brf2 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v7.41 BRF2 Ida Ertmanska Tag Q1_26_promote_green was removed from gene: BRF2.
Tag curated_removed tag was added to gene: BRF2.
Paediatric disorders - additional genes v7.41 BRF2 Ida Ertmanska Classified gene: BRF2 as No list
Paediatric disorders - additional genes v7.41 BRF2 Ida Ertmanska Gene: brf2 has been removed from the panel.
Paediatric disorders - additional genes v7.40 BRF2 Ida Ertmanska changed review comment from: Comment on list classification: There are at least 4 unrelated families with biallelic BRF2 variants and multiple congenital anomalies (+ multiple Icelandic families with a founder splice variant). The findings are not consistent and include facial dysmorphism, immunodeficiency, ID, skin rashes, contractures, polydactyly, and more. Based on the syndromic, non-specific, congenital presentation, this gene should be promoted to Green on Paediatric disorders - additional genes.; to: Comment on list classification: There are at least 4 unrelated families with biallelic BRF2 variants and multiple congenital anomalies (+ multiple Icelandic families with a founder splice variant). The findings are not consistent and include facial dysmorphism, immunodeficiency, ID, skin rashes, contractures, polydactyly, and more. The gene has been tagged for promotion on Intellectual disability, which ensures inclusion on R27. Hence, added a curated_removed tag.
Paediatric disorders - additional genes v7.40 BRF2 Ida Ertmanska edited their review of gene: BRF2: Changed phenotypes to: multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042
Intellectual disability v9.354 BRF2 Ida Ertmanska gene: BRF2 was added
gene: BRF2 was added to Intellectual disability. Sources: Literature
Q1_26_promote_green tags were added to gene: BRF2.
Mode of inheritance for gene: BRF2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BRF2 were set to 40229899; 40781771
Phenotypes for gene: BRF2 were set to multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042; intellectual disability, MONDO:0001071
Review for gene: BRF2 was set to GREEN
Added comment: PMID: 40229899 Mattioli et al., 2025
Report of six families (3 Icelandic, 1 Iranian, 1 Pakistani, 1 of unknown ancestry) with bi-allelic variants in BRF2 presenting with early mortality, brain, and craniofacial anomalies and/or neurodevelopmental disorders (NDD). Patients had phenotypes ranging from perinatal death to Treacher-Collins and craniosynostosis with radial defects and immunodeficiency or global developmental delay, hearing, and vision impairment.
Families 1-3 = Icelandic families with founder BRF2 variant c.214 + 1G > A, not much detail provided on phenotype beyond "early lethality". Genotyping was not done for the affected fetuses, it was inferred from living family members.

Family 4 - female proband with Treacher-Collins syndrome, presented with hearing impairment, soft cleft palate, microcephaly, and facial dysmorphism. She was homozygous for BRF2 c.481G > T; p.(Gly161*).

Family 5 - 2 sibs compound het for BRF2 c.782C > T ; p.(Pro261Leu) & c.404_409delinsA; p.(Met135Asnfs*15);
Patient II:1 female, presented with coronal synostosis, microcephaly, hypertelorism, a small beaked, nose, retrognathia, shortened right radius, and absent left radius, with radial deviation of the hands and contractures of all fingers. She was found to have anemia, leukocytosis, marked eosinophilia, and thrombocytopenia, and developed a significant rash by 1 month of age; she died at 2 mo from bacterial infection.
Patient II:2, male - presented with frontal bone hypoplasia with bilateral coronal synostosis, micrognathia, small orbits, low-set ears, downward slanting palpebral fissures, and significantly decreased B-cell CD19 subsets. He subsequently developed ichthyosiform erythroderma and eosinophilic myeloid hyperplasia. He had developmental and speech delays.

Family 6 - 4 affected sibs with moderate ID, and delays in motor and speech development; 2 sibs had mild hearing and vision impairment. 2 sibs confirmed homozygous for BRF2 c.31G > A; p.(Gly11Ser).

Zebrafish knocked down for the orthologous brf2 presented with abnormal escape response, reduced swimming velocity and head size, and craniofacial malformations. Phenotype was rescued by human BRF2, but not by isoforms with patients variants.

PMID: 40781771 Yoon et al., 2025
Case report of a girl, presumed Korean born to non-consanguineous parents, with multiple congenital anomalies: polydactyly of the right fifth toe, duplex kidney on the right side, hypodontia, and dysmorphic facial features. She had recurrent infections in the neonatal period, and was diagnosed with primary immunodeficiency at 4 months. Mild ID (IQ=60) was diagnosed at age 16 yrs. She harboured comp het BRF2 variants: c.379C>T, p.Arg127Ter & c.782C>T, p.Pro261Leu. Older sister was similarly affected; she died of infection at 19 months.
Single-cell RNA-seq analysis of the patient sample revealed transcriptional abnormalities in PBMCs from the patient harboring BRF2 mutations. BRF2 mutations disrupt RNA Pol III activity specifically at type III promoters, leading to transcriptional dysregulation of critical noncoding RNAs

BRF2 is not yet associated with a phenotype in OMIM (accessed 27 Mar 2026).
Sources: Literature
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v8.91 BRF2 Ida Ertmanska Phenotypes for gene: BRF2 were changed from to multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042
Primary immunodeficiency or monogenic inflammatory bowel disease v8.90 BRF2 Ida Ertmanska Classified gene: BRF2 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v8.90 BRF2 Ida Ertmanska Added comment: Comment on list classification: There are 4 individuals from 2 unrelated families with biallelic BRF2 variants and multiple non-specific congential anomalies, including primary immunodeficiency leading to early death. Early lethality was also seen in several Icelandic families with a BRF2 founder variant, though cause of death was not ascertained in those cases. Based on available evidence, this gene can only be rated Amber on this panel.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.90 BRF2 Ida Ertmanska Gene: brf2 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v8.89 BRF2 Ida Ertmanska Tag Q1_26_promote_green was removed from gene: BRF2.
Paediatric disorders - additional genes v7.40 BRF2 Ida Ertmanska Phenotypes for gene: BRF2 were changed from to multiple congenital anomalies/dysmorphic syndrome, MONDO:0019042
Paediatric disorders - additional genes v7.39 BRF2 Ida Ertmanska Classified gene: BRF2 as Amber List (moderate evidence)
Paediatric disorders - additional genes v7.39 BRF2 Ida Ertmanska Added comment: Comment on list classification: There are at least 4 unrelated families with biallelic BRF2 variants and multiple congenital anomalies (+ multiple Icelandic families with a founder splice variant). The findings are not consistent and include facial dysmorphism, immunodeficiency, ID, skin rashes, contractures, polydactyly, and more. Based on the syndromic, non-specific, congenital presentation, this gene should be promoted to Green on Paediatric disorders - additional genes.
Paediatric disorders - additional genes v7.39 BRF2 Ida Ertmanska Gene: brf2 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v7.38 BRF2 Ida Ertmanska changed review comment from: PMID: 40229899 Mattioli et al., 2025
Report of six families (3 Icelandic, 1 Iranian, 1 Pakistani, 1 of unknown ancestry) with bi-allelic variants in BRF2 presenting with early mortality, brain, and craniofacial anomalies and/or neurodevelopmental disorders (NDD). Patients had phenotypes ranging from perinatal death to Treacher-Collins and craniosynostosis with radial defects and immunodeficiency or global developmental delay, hearing, and vision impairment.
Families 1-3 = Icelandic families with founder BRF2 variant c.214 + 1G > A, not much detail provided on phenotype beyond "early lethality". Genotyping was not done for the affected fetuses, it was inferred from living family members.

Family 4 - female proband with Treacher-Collins syndrome, presented with hearing impairment, soft cleft palate, microcephaly, and facial dysmorphism. She was homozygous for BRF2 c.481G > T; p.(Gly161*).

Family 5 - 2 sibs compound het for BRF2 c.782C > T ; p.(Pro261Leu) & c.404_409delinsA; p.(Met135Asnfs*15);
Patient II:1 female, presented with coronal synostosis, microcephaly, hypertelorism, a small beaked, nose, retrognathia, shortened right radius, and absent left radius, with radial deviation of the hands and contractures of all fingers. She was found to have anemia, leukocytosis, marked eosinophilia, and thrombocytopenia, and developed a significant rash by 1 month of age; she died at 2 mo from bacterial infection.
Patient II:2, male - presented with frontal bone hypoplasia with bilateral coronal synostosis, micrognathia, small orbits, low-set ears, downward slanting palpebral fissures, and significantly decreased B-cell CD19 subsets. He subsequently developed ichthyosiform erythroderma and eosinophilic myeloid hyperplasia. He had developmental and speech delays.

Family 6 - 4 affected sibs with moderate ID, and delays in motor and speech development; 2 sibs had mild hearing and vision impairment. 2 sibs confirmed homozygous for BRF2 c.31G > A; p.(Gly11Ser).

Zebrafish knocked down for the orthologous brf2 presented with abnormal escape response, reduced swimming velocity and head size, and craniofacial malformations. Phenotype was rescued by human BRF2, but not by isoforms with patients variants.

PMID: 40781771 Yoon et al., 2025
Case report - girl with multiple congenital anomalies: polydactyly of the right fifth toe, duplex kidney on the right side, hypodontia, and dysmorphic facial features. She had recurrent infections in the neonatal period, and was diagnosed with primary immunodeficiency at 4 months. Mild ID (IQ=60) was diagnosed at age 16 yrs. She harboured comp het BRF2 variants: c.379C>T, p.Arg127Ter & c.782C>T, p.Pro261Leu. Older sister was similarly affected; she died of infection at 19 months.
Single-cell RNA-seq analysis of the patient sample revealed transcriptional abnormalities in PBMCs from the patient harboring BRF2 mutations. BRF2 mutations disrupt RNA Pol III activity specifically at type III promoters, leading to transcriptional dysregulation of critical noncoding RNAs
Sources: Literature; to: PMID: 40229899 Mattioli et al., 2025
Report of six families (3 Icelandic, 1 Iranian, 1 Pakistani, 1 of unknown ancestry) with bi-allelic variants in BRF2 presenting with early mortality, brain, and craniofacial anomalies and/or neurodevelopmental disorders (NDD). Patients had phenotypes ranging from perinatal death to Treacher-Collins and craniosynostosis with radial defects and immunodeficiency or global developmental delay, hearing, and vision impairment.
Families 1-3 = Icelandic families with founder BRF2 variant c.214 + 1G > A, not much detail provided on phenotype beyond "early lethality". Genotyping was not done for the affected fetuses, it was inferred from living family members.

Family 4 - female proband with Treacher-Collins syndrome, presented with hearing impairment, soft cleft palate, microcephaly, and facial dysmorphism. She was homozygous for BRF2 c.481G > T; p.(Gly161*).

Family 5 - 2 sibs compound het for BRF2 c.782C > T ; p.(Pro261Leu) & c.404_409delinsA; p.(Met135Asnfs*15);
Patient II:1 female, presented with coronal synostosis, microcephaly, hypertelorism, a small beaked, nose, retrognathia, shortened right radius, and absent left radius, with radial deviation of the hands and contractures of all fingers. She was found to have anemia, leukocytosis, marked eosinophilia, and thrombocytopenia, and developed a significant rash by 1 month of age; she died at 2 mo from bacterial infection.
Patient II:2, male - presented with frontal bone hypoplasia with bilateral coronal synostosis, micrognathia, small orbits, low-set ears, downward slanting palpebral fissures, and significantly decreased B-cell CD19 subsets. He subsequently developed ichthyosiform erythroderma and eosinophilic myeloid hyperplasia. He had developmental and speech delays.

Family 6 - 4 affected sibs with moderate ID, and delays in motor and speech development; 2 sibs had mild hearing and vision impairment. 2 sibs confirmed homozygous for BRF2 c.31G > A; p.(Gly11Ser).

Zebrafish knocked down for the orthologous brf2 presented with abnormal escape response, reduced swimming velocity and head size, and craniofacial malformations. Phenotype was rescued by human BRF2, but not by isoforms with patients variants.

PMID: 40781771 Yoon et al., 2025
Case report of a girl, presumed Korean born to non-consanguineous parents, with multiple congenital anomalies: polydactyly of the right fifth toe, duplex kidney on the right side, hypodontia, and dysmorphic facial features. She had recurrent infections in the neonatal period, and was diagnosed with primary immunodeficiency at 4 months. Mild ID (IQ=60) was diagnosed at age 16 yrs. She harboured comp het BRF2 variants: c.379C>T, p.Arg127Ter & c.782C>T, p.Pro261Leu. Older sister was similarly affected; she died of infection at 19 months.
Single-cell RNA-seq analysis of the patient sample revealed transcriptional abnormalities in PBMCs from the patient harboring BRF2 mutations. BRF2 mutations disrupt RNA Pol III activity specifically at type III promoters, leading to transcriptional dysregulation of critical noncoding RNAs

BRF2 is not yet associated with a phenotype in OMIM (accessed 27 Mar 2026).
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v8.89 BRF2 Ida Ertmanska gene: BRF2 was added
gene: BRF2 was added to Primary immunodeficiency or monogenic inflammatory bowel disease. Sources: Literature
Q1_26_promote_green tags were added to gene: BRF2.
Mode of inheritance for gene: BRF2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BRF2 were set to 40229899; 40781771
Review for gene: BRF2 was set to GREEN
Added comment: PMID: 40229899 Mattioli et al., 2025
Report of six families (3 Icelandic, 1 Iranian, 1 Pakistani, 1 of unknown ancestry) with bi-allelic variants in BRF2 presenting with early mortality, brain, and craniofacial anomalies and/or neurodevelopmental disorders (NDD). Patients had phenotypes ranging from perinatal death to Treacher-Collins and craniosynostosis with radial defects and immunodeficiency or global developmental delay, hearing, and vision impairment.
Families 1-3 = Icelandic families with founder BRF2 variant c.214 + 1G > A, not much detail provided on phenotype beyond "early lethality". Genotyping was not done for the affected fetuses, it was inferred from living family members.

Family 4 - female proband with Treacher-Collins syndrome, presented with hearing impairment, soft cleft palate, microcephaly, and facial dysmorphism. She was homozygous for BRF2 c.481G > T; p.(Gly161*).

Family 5 - 2 sibs compound het for BRF2 c.782C > T ; p.(Pro261Leu) & c.404_409delinsA; p.(Met135Asnfs*15);
Patient II:1 female, presented with coronal synostosis, microcephaly, hypertelorism, a small beaked, nose, retrognathia, shortened right radius, and absent left radius, with radial deviation of the hands and contractures of all fingers. She was found to have anemia, leukocytosis, marked eosinophilia, and thrombocytopenia, and developed a significant rash by 1 month of age; she died at 2 mo from bacterial infection.
Patient II:2, male - presented with frontal bone hypoplasia with bilateral coronal synostosis, micrognathia, small orbits, low-set ears, downward slanting palpebral fissures, and significantly decreased B-cell CD19 subsets. He subsequently developed ichthyosiform erythroderma and eosinophilic myeloid hyperplasia. He had developmental and speech delays.

Family 6 - 4 affected sibs with moderate ID, and delays in motor and speech development; 2 sibs had mild hearing and vision impairment. 2 sibs confirmed homozygous for BRF2 c.31G > A; p.(Gly11Ser).

Zebrafish knocked down for the orthologous brf2 presented with abnormal escape response, reduced swimming velocity and head size, and craniofacial malformations. Phenotype was rescued by human BRF2, but not by isoforms with patients variants.

PMID: 40781771 Yoon et al., 2025
Case report - girl with multiple congenital anomalies: polydactyly of the right fifth toe, duplex kidney on the right side, hypodontia, and dysmorphic facial features. She had recurrent infections in the neonatal period, and was diagnosed with primary immunodeficiency at 4 months. Mild ID (IQ=60) was diagnosed at age 16 yrs. She harboured comp het BRF2 variants: c.379C>T, p.Arg127Ter & c.782C>T, p.Pro261Leu. Older sister was similarly affected; she died of infection at 19 months.
Single-cell RNA-seq analysis of the patient sample revealed transcriptional abnormalities in PBMCs from the patient harboring BRF2 mutations. BRF2 mutations disrupt RNA Pol III activity specifically at type III promoters, leading to transcriptional dysregulation of critical noncoding RNAs
Sources: Literature
Paediatric disorders - additional genes v7.38 BRF2 Ida Ertmanska gene: BRF2 was added
gene: BRF2 was added to Paediatric disorders - additional genes. Sources: Literature
Q1_26_promote_green tags were added to gene: BRF2.
Mode of inheritance for gene: BRF2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BRF2 were set to 40229899; 40781771
Review for gene: BRF2 was set to GREEN
Added comment: PMID: 40229899 Mattioli et al., 2025
Report of six families (3 Icelandic, 1 Iranian, 1 Pakistani, 1 of unknown ancestry) with bi-allelic variants in BRF2 presenting with early mortality, brain, and craniofacial anomalies and/or neurodevelopmental disorders (NDD). Patients had phenotypes ranging from perinatal death to Treacher-Collins and craniosynostosis with radial defects and immunodeficiency or global developmental delay, hearing, and vision impairment.
Families 1-3 = Icelandic families with founder BRF2 variant c.214 + 1G > A, not much detail provided on phenotype beyond "early lethality". Genotyping was not done for the affected fetuses, it was inferred from living family members.

Family 4 - female proband with Treacher-Collins syndrome, presented with hearing impairment, soft cleft palate, microcephaly, and facial dysmorphism. She was homozygous for BRF2 c.481G > T; p.(Gly161*).

Family 5 - 2 sibs compound het for BRF2 c.782C > T ; p.(Pro261Leu) & c.404_409delinsA; p.(Met135Asnfs*15);
Patient II:1 female, presented with coronal synostosis, microcephaly, hypertelorism, a small beaked, nose, retrognathia, shortened right radius, and absent left radius, with radial deviation of the hands and contractures of all fingers. She was found to have anemia, leukocytosis, marked eosinophilia, and thrombocytopenia, and developed a significant rash by 1 month of age; she died at 2 mo from bacterial infection.
Patient II:2, male - presented with frontal bone hypoplasia with bilateral coronal synostosis, micrognathia, small orbits, low-set ears, downward slanting palpebral fissures, and significantly decreased B-cell CD19 subsets. He subsequently developed ichthyosiform erythroderma and eosinophilic myeloid hyperplasia. He had developmental and speech delays.

Family 6 - 4 affected sibs with moderate ID, and delays in motor and speech development; 2 sibs had mild hearing and vision impairment. 2 sibs confirmed homozygous for BRF2 c.31G > A; p.(Gly11Ser).

Zebrafish knocked down for the orthologous brf2 presented with abnormal escape response, reduced swimming velocity and head size, and craniofacial malformations. Phenotype was rescued by human BRF2, but not by isoforms with patients variants.

PMID: 40781771 Yoon et al., 2025
Case report - girl with multiple congenital anomalies: polydactyly of the right fifth toe, duplex kidney on the right side, hypodontia, and dysmorphic facial features. She had recurrent infections in the neonatal period, and was diagnosed with primary immunodeficiency at 4 months. Mild ID (IQ=60) was diagnosed at age 16 yrs. She harboured comp het BRF2 variants: c.379C>T, p.Arg127Ter & c.782C>T, p.Pro261Leu. Older sister was similarly affected; she died of infection at 19 months.
Single-cell RNA-seq analysis of the patient sample revealed transcriptional abnormalities in PBMCs from the patient harboring BRF2 mutations. BRF2 mutations disrupt RNA Pol III activity specifically at type III promoters, leading to transcriptional dysregulation of critical noncoding RNAs
Sources: Literature
Retinal disorders v8.108 BBIP1 Ida Ertmanska Tag Q1_26_promote_green tag was added to gene: BBIP1.
Bardet Biedl syndrome v2.13 BBIP1 Ida Ertmanska changed review comment from: PMID: 37239474 Nawaz et al., 2023
Homozygous nonsense mutation (c.160A>T; p.Lys54Ter) in the BBIP1 (NM_001195306.1) gene in family B (Pakistani origin). Affected individual with suspected Bardet–Biedl Syndrome presented with polydactyly, retinal degeneration, obesity, hypogonadism, and renal abnormality. No ID/DD seen.

PMID: 32055034 Shamseldin et al., 2020
A patient with classical BBS (18DG0012) harboured a homozygous novel variant NM_001195305.1:c.38–6T > C (aberrant splicing confirmed by RT-PCR with 86% NMD.

PMID: 24026985 Scheidecker et al., 2014
Italian BBS patient with a homozygous stop mutation (NM_001195306: c.173T>G, p.Leu58*) in the BBIP1 gene. No BBIP1 protein could be detected in fibroblasts from the patient. He presented with retinitis pigmentosa, obesity, kidney failure, cognitive disability, and brachydactyly. He was diagnosed as affected with BBS at 49 years old. He presented an end-stage renal failure 4 years after the diagnosis.; to: PMID: 37239474 Nawaz et al., 2023
Homozygous nonsense mutation (c.160A>T; p.Lys54Ter) in the BBIP1 (NM_001195306.1) gene in family B (Pakistani origin). Affected individual with suspected Bardet–Biedl Syndrome presented with polydactyly, retinal degeneration, obesity, hypogonadism, and renal abnormality. No ID/DD seen.

PMID: 32055034 Shamseldin et al., 2020
A patient with classical BBS (18DG0012) harboured a homozygous novel variant NM_001195305.1:c.38–6T > C (aberrant splicing confirmed by RT-PCR with 86% NMD. OMIM entry states "The patient was reported to have classic features of BBS, with obesity, impaired intellectual development, polydactyly, and end-stage retinitis pigmentosa." but I was not able to verify this in the primary publication.

PMID: 24026985 Scheidecker et al., 2014
Italian BBS patient with a homozygous stop mutation (NM_001195306: c.173T>G, p.Leu58*) in the BBIP1 gene. No BBIP1 protein could be detected in fibroblasts from the patient. He presented with retinitis pigmentosa, obesity, kidney failure, cognitive disability, and brachydactyly. He was diagnosed as affected with BBS at 49 years old. He presented an end-stage renal failure 4 years after the diagnosis.
Renal ciliopathies v4.14 BBIP1 Ida Ertmanska Phenotypes for gene: BBIP1 were changed from ?Bardet-Biedl syndrome 18, 615995 to Bardet-Biedl syndrome 18, OMIM:615995
Renal ciliopathies v4.13 BBIP1 Ida Ertmanska Publications for gene: BBIP1 were set to 24026985; 32055034
Renal ciliopathies v4.12 BBIP1 Ida Ertmanska Classified gene: BBIP1 as Amber List (moderate evidence)
Renal ciliopathies v4.12 BBIP1 Ida Ertmanska Added comment: Comment on list classification: There are 3 individuals reported in literature with biallelic BBIP1 variants and Bardet-Biedl syndrome. Renal dysfunction was confirmed in 2 unrelated patients. Moreover, zebrafish bbip1 knockdown resulted in a ciliopathy phenotype, including bilateral cystic dilations of the pronephros. Hence, this gene should be promoted to Green at the next update.
Renal ciliopathies v4.12 BBIP1 Ida Ertmanska Gene: bbip1 has been classified as Amber List (Moderate Evidence).
Renal ciliopathies v4.11 BBIP1 Ida Ertmanska Tag Q1_26_promote_green tag was added to gene: BBIP1.
Renal ciliopathies v4.11 BBIP1 Ida Ertmanska reviewed gene: BBIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24026985, 32055034, 37239474; Phenotypes: Bardet-Biedl syndrome 18, OMIM:615995; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v8.108 BBIP1 Ida Ertmanska Phenotypes for gene: BBIP1 were changed from Bardet-Biedl syndrome 18, OMIM:615995 to Bardet-Biedl syndrome 18, OMIM:615995; Bardet-Biedl syndrome 18, MONDO:0014446
Ophthalmological ciliopathies v5.18 BBIP1 Ida Ertmanska Phenotypes for gene: BBIP1 were changed from ?Bardet-Biedl syndrome 18, 615995 to Bardet-Biedl syndrome 18, OMIM:615995
Ophthalmological ciliopathies v5.17 BBIP1 Ida Ertmanska Publications for gene: BBIP1 were set to 24026985
Ophthalmological ciliopathies v5.16 BBIP1 Ida Ertmanska Classified gene: BBIP1 as Amber List (moderate evidence)
Ophthalmological ciliopathies v5.16 BBIP1 Ida Ertmanska Added comment: Comment on list classification: There are 3 unrelated individuals reported in literature with biallelic BBIP1 variants and Bardet-Biedl syndrome. Retinal degeneration was confirmed in 2 unrelated patients. Moreover, zebrafish bbip1 knockdown resulted in a ciliopathy phenotype, including abnormal retinal development. Hence, this gene should be promoted to Green at the next update.
Ophthalmological ciliopathies v5.16 BBIP1 Ida Ertmanska Gene: bbip1 has been classified as Amber List (Moderate Evidence).
Ophthalmological ciliopathies v5.15 BBIP1 Ida Ertmanska Tag Q1_26_promote_green tag was added to gene: BBIP1.
Ophthalmological ciliopathies v5.15 BBIP1 Ida Ertmanska reviewed gene: BBIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24026985, 32055034, 37239474; Phenotypes: Bardet-Biedl syndrome 18, OMIM:615995; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v8.107 BBIP1 Ida Ertmanska Phenotypes for gene: BBIP1 were changed from Genetic Retinal Degeneration Conditions to Bardet-Biedl syndrome 18, OMIM:615995
Retinal disorders v8.106 BBIP1 Ida Ertmanska Publications for gene: BBIP1 were set to PMID: 24026985 - Scheidecker et al (2014) Exome sequencing of Bardet-Biedl syndrome patient identifies a null mutation in the BBSome subunit BBIP1 (BBS18). J Med Genet. 2014 Feb; 51(2):132-6. - Report a novel homozygous nonsense mutation, c.173T>G, p.Leu58Ter. Het in father; mother and sibling's samples not available for testing. Three functional assays confirm that this mutation has a major biological effect underlying the phenotype observed in the patient. PMID: 1908107 - publication describing function of the protein.
Retinal disorders v8.105 BBIP1 Ida Ertmanska Mode of inheritance for gene: BBIP1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v8.104 BBIP1 Ida Ertmanska Classified gene: BBIP1 as Amber List (moderate evidence)
Retinal disorders v8.104 BBIP1 Ida Ertmanska Added comment: Comment on list classification: There are 3 individuals reported in literature with biallelic BBIP1 variants and Bardet-Biedl syndrome. Retinal degeneration was confirmed in 2 unrelated patients. Moreover, zebrafish bbip1 knockdown resulted in abnormal retinal development. Hence, this gene should be promoted to Green at the next update.
Retinal disorders v8.104 BBIP1 Ida Ertmanska Gene: bbip1 has been classified as Amber List (Moderate Evidence).
Retinal disorders v8.103 BBIP1 Ida Ertmanska reviewed gene: BBIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24026985, 32055034, 37239474; Phenotypes: Bardet-Biedl syndrome 18, OMIM:615995; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Limb disorders v7.25 BBIP1 Ida Ertmanska Phenotypes for gene: BBIP1 were changed from ?Bardet-Biedl syndrome 18, 615995 to Bardet-Biedl syndrome 18, OMIM:615995
Limb disorders v7.24 BBIP1 Ida Ertmanska Publications for gene: BBIP1 were set to 24026985
Limb disorders v7.23 BBIP1 Ida Ertmanska Classified gene: BBIP1 as Amber List (moderate evidence)
Limb disorders v7.23 BBIP1 Ida Ertmanska Added comment: Comment on list classification: 2 patients reported in literature with BBS and biallelic BBIP1 variants had polydactyly / brachydactyly. Hence, this gene can only be rated Amber on Limb disorders given available evidence.
Limb disorders v7.23 BBIP1 Ida Ertmanska Gene: bbip1 has been classified as Amber List (Moderate Evidence).
Limb disorders v7.22 BBIP1 Ida Ertmanska changed review comment from: PMID: 37239474 Nawaz et al., 2023
Homozygous nonsense mutation (c.160A>T; p.Lys54Ter) in the BBIP1 (NM_001195306.1) gene in family B (Pakistani origin). Affected individual with suspected Bardet–Biedl Syndrome presented with polydactyly, retinal degeneration, obesity, hypogonadism, and renal abnormality. No ID/DD seen.

PMID: 32055034 Shamseldin et al., 2020
A patient with classical BBS (18DG0012) harboured a homozygous novel variant NM_001195305.1:c.38–6T > C (aberrant splicing confirmed by RT-PCR with 86% NMD.

PMID: 24026985 Scheidecker et al., 2014
Italian BBS patient with a homozygous stop mutation (NM_001195306: c.173T>G, p.Leu58*) in the BBIP1 gene. No BBIP1 protein could be detected in fibroblasts from the patient. He presented with retinitis pigmentosa, obesity, kidney failure, cognitive disability, and brachydactyly. He was diagnosed as affected with BBS at 49 years old. He presented an end-stage renal failure 4 years after the diagnosis.; to: PMID: 37239474 Nawaz et al., 2023
Homozygous nonsense mutation (c.160A>T; p.Lys54Ter) in the BBIP1 (NM_001195306.1) gene in family B (Pakistani origin). Affected individual with suspected Bardet–Biedl Syndrome presented with polydactyly, retinal degeneration, obesity, hypogonadism, and renal abnormality. No ID/DD seen.

PMID: 32055034 Shamseldin et al., 2020
A patient with classical BBS (18DG0012) harboured a homozygous novel variant NM_001195305.1:c.38–6T > C (aberrant splicing confirmed by RT-PCR with 86% NMD. No phenotypic details provided.

PMID: 24026985 Scheidecker et al., 2014
Italian BBS patient with a homozygous stop mutation (NM_001195306: c.173T>G, p.Leu58*) in the BBIP1 gene. No BBIP1 protein could be detected in fibroblasts from the patient. He presented with retinitis pigmentosa, obesity, kidney failure, cognitive disability, and brachydactyly. He was diagnosed as affected with BBS at 49 years old. He presented an end-stage renal failure 4 years after the diagnosis.
Limb disorders v7.22 BBIP1 Ida Ertmanska reviewed gene: BBIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24026985, 32055034, 37239474; Phenotypes: Bardet-Biedl syndrome 18, OMIM:615995; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Bardet Biedl syndrome v2.13 BBIP1 Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotype updated on 27 Mar 2026.
Bardet Biedl syndrome v2.13 BBIP1 Ida Ertmanska Phenotypes for gene: BBIP1 were changed from Bardet-Biedl syndrome 18, OMIM:615995; Bardet-Biedl syndrome 18, MONDO:0014446 to Bardet-Biedl syndrome 18, OMIM:615995; Bardet-Biedl syndrome 18, MONDO:0014446
Bardet Biedl syndrome v2.12 BBIP1 Ida Ertmanska Phenotypes for gene: BBIP1 were changed from ?Bardet-Biedl syndrome 18, 615995 to Bardet-Biedl syndrome 18, OMIM:615995; Bardet-Biedl syndrome 18, MONDO:0014446
Bardet Biedl syndrome v2.11 BBIP1 Ida Ertmanska Publications for gene: BBIP1 were set to 24026985
Bardet Biedl syndrome v2.10 BBIP1 Ida Ertmanska Classified gene: BBIP1 as Amber List (moderate evidence)
Bardet Biedl syndrome v2.10 BBIP1 Ida Ertmanska Added comment: Comment on list classification: There are now 3 unrelated individuals reported with biallelic BBIP1 variants and Bardet Biedl syndrome diagnosis. Hence, this gene should be promoted to Green at the next update.
Bardet Biedl syndrome v2.10 BBIP1 Ida Ertmanska Gene: bbip1 has been classified as Amber List (Moderate Evidence).
Bardet Biedl syndrome v2.9 BBIP1 Ida Ertmanska Tag Q1_26_promote_green tag was added to gene: BBIP1.
Bardet Biedl syndrome v2.9 BBIP1 Ida Ertmanska reviewed gene: BBIP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 24026985, 32055034, 37239474; Phenotypes: Bardet-Biedl syndrome 18, OMIM:615995; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v5.54 NRDC Ida Ertmanska Classified gene: NRDC as Amber List (moderate evidence)
Optic neuropathy v5.54 NRDC Ida Ertmanska Added comment: Comment on list classification: There are 3 individuals reported with optic atrophy and biallelic NRDC variants. Hence, this gene should be promoted to Green at the next update.
Optic neuropathy v5.54 NRDC Ida Ertmanska Gene: nrdc has been classified as Amber List (Moderate Evidence).
Severe microcephaly v8.41 NRDC Ida Ertmanska Classified gene: NRDC as Amber List (moderate evidence)
Severe microcephaly v8.41 NRDC Ida Ertmanska Added comment: Comment on list classification: There are 13 individuals reported with biallelic NRDC variants and microcephaly. While severity is not stated, this is a consistent feature in all patients. Hence, NRDC should be promoted to Green for Severe microcephaly, with MOI set to BIALLELIC, autosomal or pseudoautosomal.
Severe microcephaly v8.41 NRDC Ida Ertmanska Gene: nrdc has been classified as Amber List (Moderate Evidence).
Optic neuropathy v5.53 NRDC Ida Ertmanska gene: NRDC was added
gene: NRDC was added to Optic neuropathy. Sources: Literature
Q1_26_promote_green tags were added to gene: NRDC.
Mode of inheritance for gene: NRDC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NRDC were set to 41734767
Phenotypes for gene: NRDC were set to microcephaly, MONDO:0001149; neurodevelopmental disorder, MONDO:0700092; Optic neuropathy, HP:0001138
Review for gene: NRDC was set to GREEN
Added comment: PMID: 41734767 Pehlivan et al., 2026
Report of 14 individuals from nine unrelated families carrying homozygous NRDC pathogenic variants (some reported previously). Common clinical features include severe to profound developmental delay/intellectual disability (12/12), microcephaly (13/13), prematurity (5/13), lethality in the first 3 years of life (9/14), seizures (7/11), joint contractures (4/8), eye/visual abnormalities (5/7 - 3 with optic atrophy, 1 with nystagmus, and 1 case of visual inattentiveness), and abnormal brain imaging studies ranging from diffuse atrophy to lissencephaly (8/11). The identified variants include two splice, three frameshift, and three missense variants.

NRDC is not yet associated with a phenotype in OMIM (accessed 9th Mar 2026).
Sources: Literature
Severe microcephaly v8.40 NRDC Ida Ertmanska gene: NRDC was added
gene: NRDC was added to Severe microcephaly. Sources: Literature
Q1_26_promote_green tags were added to gene: NRDC.
Mode of inheritance for gene: NRDC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NRDC were set to 41734767
Phenotypes for gene: NRDC were set to microcephaly, MONDO:0001149; neurodevelopmental disorder, MONDO:0700092; Optic neuropathy, HP:0001138
Review for gene: NRDC was set to GREEN
Added comment: PMID: 41734767 Pehlivan et al., 2026
Report of 14 individuals from nine unrelated families carrying homozygous NRDC pathogenic variants (some reported previously). Common clinical features include severe to profound developmental delay/intellectual disability (12/12), microcephaly (13/13), prematurity (5/13), lethality in the first 3 years of life (9/14), seizures (7/11), joint contractures (4/8), eye/visual abnormalities (5/7 - 3 with optic atrophy, 1 with nystagmus, and 1 case of visual inattentiveness), and abnormal brain imaging studies ranging from diffuse atrophy to lissencephaly (8/11). The identified variants include two splice, three frameshift, and three missense variants.

NRDC is not yet associated with a phenotype in OMIM (accessed 9th Mar 2026).
Sources: Literature
Severe microcephaly v8.39 TYW1 Ida Ertmanska changed review comment from: Comment on list classification: There are 2 sibs reported in literature with a biallelic TYW1 variant and severe microcephaly (more than -3 SD). Based on available evidence, this gene can only be rated Red on this panel.; to: Comment on list classification: There are 2 sibs reported in literature with a biallelic TYW1 variant and severe microcephaly (more than -3 SD). Mouse and zebrafish knockout models showed microcephaly, supportive of the disease association. Based on available evidence, this gene can only be rated Amber on this panel.
Severe microcephaly v8.39 TYW1 Ida Ertmanska Classified gene: TYW1 as Amber List (moderate evidence)
Severe microcephaly v8.39 TYW1 Ida Ertmanska Gene: tyw1 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v8.38 TYW1 Ida Ertmanska changed review comment from: PMID: 34077496 Li et al., 2021
2 Chinese sibs (non-consanguineous parents) reported with comp het TYW1 variants: NM_018264: c.616C>T, p.R206C & c.1166G>A, p. R389Q.
Proband CP_012_1, male - Wechsler Preschool and Primary Scale of Intelligence IQ = 40 at 7 years old (moderate ID); head circumference at 6yrs: 47.5 cm (−3.26 SD).
CP_012_2, older sister - diagnosed with mixed type cerebral palsy (spasticity, dyskinesia), IQ <50 (moderate ID). Head circumference was 49 cm at 14yrs (−3.64 SD).
Parents confirmed heterozygous for 1 variant each. TYW1:c.616C>T - MAF in gnomADv4 = 0.0004900, including 1 homozygote. TYW1:c.1166G>A MAF in gnomAD v4 = 0.0001559, no homozygotes.

Functional evidence: TYW1 protein levels dramatically reduced in proband compared to controls; tyw1 deficiency in zebrafish resulted in ectopic neuronal cell migration in the brain and undifferentiated motor neuronal cells in the spinal cord - this was rescued by WT human and zebrafish tyw1 mRNA, but not by mRNA with patients' mutations. In addition, tyw1 knockdown zebrafish showed recuded swimming capacity. Kncokout tyw1-/- mice showed impaired motor function and reduced cognition in behavioural tests.

PMID: 38706838 Sun et al., 2024
Fucntional evidence: Study used brain organoid model and human embryonic stem cells to show that translation efficiency of UUU codon was compromised in TYW1−/− cells. Also, neuron differentiation was impaired when TYW1 was depleted.

TYW1 is not yet associated with a phenotype in OMIM, ClinGen or G2P (accessed 17 Mar 2026).
Sources: Literature; to: PMID: 34077496 Li et al., 2021
2 Chinese sibs (non-consanguineous parents) reported with comp het TYW1 variants: NM_018264: c.616C>T, p.R206C & c.1166G>A, p. R389Q.
Proband CP_012_1, male - Wechsler Preschool and Primary Scale of Intelligence IQ = 40 at 7 years old (moderate ID); head circumference at 6yrs: 47.5 cm (−3.26 SD).
CP_012_2, older sister - diagnosed with mixed type cerebral palsy (spasticity, dyskinesia), IQ <50 (moderate ID). Head circumference was 49 cm at 14yrs (−3.64 SD).
Parents confirmed heterozygous for 1 variant each. TYW1:c.616C>T - MAF in gnomADv4 = 0.0004900, including 1 homozygote. TYW1:c.1166G>A MAF in gnomAD v4 = 0.0001559, no homozygotes.

Functional evidence: TYW1 protein levels dramatically reduced in proband compared to controls; tyw1 deficiency in zebrafish resulted in ectopic neuronal cell migration in the brain and undifferentiated motor neuronal cells in the spinal cord - this was rescued by WT human and zebrafish tyw1 mRNA, but not by mRNA with patients' mutations. In addition, tyw1 knockdown zebrafish showed recuded swimming capacity. Kncokout tyw1-/- mice showed impaired motor function and reduced cognition in behavioural tests. Microcephaly and neurological manifestation were observed in both mice and zebrafish.

PMID: 38706838 Sun et al., 2024
Fucntional evidence: Study used brain organoid model and human embryonic stem cells to show that translation efficiency of UUU codon was compromised in TYW1−/− cells. Also, neuron differentiation was impaired when TYW1 was depleted.

TYW1 is not yet associated with a phenotype in OMIM, ClinGen or G2P (accessed 17 Mar 2026).
Sources: Literature
Severe microcephaly v8.38 TYW1 Ida Ertmanska changed review comment from: Comment on list classification: There are 2 sibs reported in literature with a biallelic TYW1 variant and severe microcephaly (more than -3 SD). Based on available evidence, this gene can only be rated Red.; to: Comment on list classification: There are 2 sibs reported in literature with a biallelic TYW1 variant and severe microcephaly (more than -3 SD). Based on available evidence, this gene can only be rated Red on this panel.
Severe microcephaly v8.38 TYW1 Ida Ertmanska Tag watchlist was removed from gene: TYW1.
Severe microcephaly v8.38 TYW1 Ida Ertmanska Classified gene: TYW1 as Red List (low evidence)
Severe microcephaly v8.38 TYW1 Ida Ertmanska Added comment: Comment on list classification: There are 2 sibs reported in literature with a biallelic TYW1 variant and severe microcephaly (more than -3 SD). Based on available evidence, this gene can only be rated Red.
Severe microcephaly v8.38 TYW1 Ida Ertmanska Gene: tyw1 has been classified as Red List (Low Evidence).
Severe microcephaly v8.37 TYW1 Ida Ertmanska gene: TYW1 was added
gene: TYW1 was added to Severe microcephaly. Sources: Literature
watchlist tags were added to gene: TYW1.
Mode of inheritance for gene: TYW1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TYW1 were set to 34077496
Phenotypes for gene: TYW1 were set to cerebral palsy, MONDO:0006497; microcephaly, MONDO:0001149
Review for gene: TYW1 was set to AMBER
Added comment: PMID: 34077496 Li et al., 2021
2 Chinese sibs (non-consanguineous parents) reported with comp het TYW1 variants: NM_018264: c.616C>T, p.R206C & c.1166G>A, p. R389Q.
Proband CP_012_1, male - Wechsler Preschool and Primary Scale of Intelligence IQ = 40 at 7 years old (moderate ID); head circumference at 6yrs: 47.5 cm (−3.26 SD).
CP_012_2, older sister - diagnosed with mixed type cerebral palsy (spasticity, dyskinesia), IQ <50 (moderate ID). Head circumference was 49 cm at 14yrs (−3.64 SD).
Parents confirmed heterozygous for 1 variant each. TYW1:c.616C>T - MAF in gnomADv4 = 0.0004900, including 1 homozygote. TYW1:c.1166G>A MAF in gnomAD v4 = 0.0001559, no homozygotes.

Functional evidence: TYW1 protein levels dramatically reduced in proband compared to controls; tyw1 deficiency in zebrafish resulted in ectopic neuronal cell migration in the brain and undifferentiated motor neuronal cells in the spinal cord - this was rescued by WT human and zebrafish tyw1 mRNA, but not by mRNA with patients' mutations. In addition, tyw1 knockdown zebrafish showed recuded swimming capacity. Kncokout tyw1-/- mice showed impaired motor function and reduced cognition in behavioural tests.

PMID: 38706838 Sun et al., 2024
Fucntional evidence: Study used brain organoid model and human embryonic stem cells to show that translation efficiency of UUU codon was compromised in TYW1−/− cells. Also, neuron differentiation was impaired when TYW1 was depleted.

TYW1 is not yet associated with a phenotype in OMIM, ClinGen or G2P (accessed 17 Mar 2026).
Sources: Literature
Childhood onset hereditary spastic paraplegia v8.44 TYW1 Ida Ertmanska changed review comment from: Comment on list classification: There is one pedigree reported in literature linking biallelic TYW1 variants to cerebral palsy with intellectual disability. There is also good functional evidence in zebrafish, mouse, and human brain organoids supporting TYW1 role in motor function and cognition. Based on available evidence, this gene can only be rated Amber for now.; to: Comment on list classification: There is one pedigree reported in literature linking biallelic TYW1 variants to cerebral palsy with intellectual disability. There is also good functional evidence in zebrafish, mouse, and human brain organoids supporting TYW1 role in motor function and cognition. Based on available evidence, this gene can only be rated Amber for now. The gene should be tagged for expert review if sufficient evidence arises to promote to green, to get views if HSP is the right panel for cerebral palsy cases.
Intestinal failure or congenital diarrhoea v3.10 PSMB10 Ida Ertmanska edited their review of gene: PSMB10: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intestinal failure or congenital diarrhoea v3.10 PSMB10 Ida Ertmanska Classified gene: PSMB10 as Amber List (moderate evidence)
Intestinal failure or congenital diarrhoea v3.10 PSMB10 Ida Ertmanska Added comment: Comment on list classification: There are at least 6 individuals reported in literature with monoallelic PSMB10 variants and SCID-Omenn syndrome, which includes congential diarrhea. Hence, this gene should be promoted to Green at the next update, with MOI set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted.
Intestinal failure or congenital diarrhoea v3.10 PSMB10 Ida Ertmanska Gene: psmb10 has been classified as Amber List (Moderate Evidence).
Intestinal failure or congenital diarrhoea v3.9 PSMB10 Ida Ertmanska Mode of inheritance for gene: PSMB10 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Autoinflammatory disorders v2.39 PSMB10 Ida Ertmanska Classified gene: PSMB10 as Amber List (moderate evidence)
Autoinflammatory disorders v2.39 PSMB10 Ida Ertmanska Added comment: Comment on list classification: There are now more than 3 cases reported with both mono- and bi- allelic PSMB10 variants - presenting with a proteasome-associated autoinflammatory syndrome (with or without recurrent infections and chronic diarrhea). Hence, the MOI should be updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal.
Autoinflammatory disorders v2.39 PSMB10 Ida Ertmanska Gene: psmb10 has been classified as Amber List (Moderate Evidence).
Intestinal failure or congenital diarrhoea v3.8 PSMB10 Ida Ertmanska gene: PSMB10 was added
gene: PSMB10 was added to Intestinal failure or congenital diarrhoea. Sources: Literature
Q1_26_promote_green tags were added to gene: PSMB10.
Mode of inheritance for gene: PSMB10 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PSMB10 were set to 31783057; 36250618; 37600812; 38503300; 39734035
Phenotypes for gene: PSMB10 were set to Immunodeficiency 121 with autoinflammation, OMIM:620807; Proteasome-associated autoinflammatory syndrome 5, OMIM:619175
Review for gene: PSMB10 was set to GREEN
Added comment: MONOALLELIC CASES:
PMID: 36250618 Hebert et al., 2022
Patient 1 - severe combined immunodeficiency (SCID), ectodermal dysplasia, alopecia, hypodontia and anonychia; het de novo PSMB10 NM_002801.3: c.601G>A p.(Gly201Arg) variant.

PMID: 38503300 van der Made et al., 2024
Identified de novo PSMB10 mutations in 6 infants with SCID-Omenn syndrome. The syndromic presentation includes severe combined immunodeficiency (SCID), as well as diarrhea (6/6), alopecia (4/5), and desquamating erythematous rash (6/6). Reported variants: PSMB10: c.166G>C, p.Asp56His and c.601G>A/c.601G>C, p.Gly201Arg.

PMID: 39734035 Kuehn et al., 2025
Case report: white female with SCID, failure to thrive, diarrhea, and pruritic rash - symptom onset at 5-9 months. Trio WES identified a de novo PSMB10 variant in the proband: c.601G>A, p.Gly201Arg.

https://doi.org/10.70962/jhi.20250096 Fournier et al., 2025
Report of 3 patients with WES detected de novo heterozygous PSMB10 variants: c.614A>C p.Asp205Ala for PI and c.623C>T p.Ser208Phe for PII and PIII. Presentation: combined immunodeficiency (3/3), generalized erythroderma with desquamation (1/3), chronic diarrhea (2/3), severe liver disease (2/3).
Functional evidence: PSMB10 constructs were expressed in HEK293T cells prior to SDS-PAGE/western blotting analysis. The p.Asp205Ala and p.Ser208Phe PSMB10 variants were shown to impair proteasome assembly and exert dominant-negative effects on PSMB9 expression.

BIALLELIC CASES:
PMID: 31783057 Sarrabay et al., 2020
3yo girl with a proteasome-associated autoinflammatory syndrome, homozygous for a PSMB10 c.41T>C, p.Phe14Ser variant. She presented with failure to thrive, cutaneous rash, and hepatosplenomegaly. No immunodeficiency.

PMID: 37600812 Papendorf et al., 2023
Three unrelated Brazilian patients present with four novel PSMB10 variants. All share the p.Phe14del variant plus a different novel variant: p.Gly167Asp, p.Cys83Leufs*123, and c.710+1G>C. All 3 patients had skin lesions, recurrent fevers, failure to thrive; microcytic anemia ascertained in 2/3.

PSMB10 is now associated with AD Immunodeficiency 121 with autoinflammation, MIM:620807 & AR Proteasome-associated autoinflammatory syndrome 5, MIM:619175 (OMIM accessed 10th Mar 2026).
Sources: Literature
Autoinflammatory disorders v2.38 PSMB10 Ida Ertmanska gene: PSMB10 was added
gene: PSMB10 was added to Autoinflammatory disorders. Sources: Literature
Q1_26_promote_green tags were added to gene: PSMB10.
Mode of inheritance for gene: PSMB10 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PSMB10 were set to 31783057; 36250618; 37600812; 38503300; 39734035
Phenotypes for gene: PSMB10 were set to Immunodeficiency 121 with autoinflammation, OMIM:620807; Proteasome-associated autoinflammatory syndrome 5, OMIM:619175
Review for gene: PSMB10 was set to GREEN
Added comment: MONOALLELIC CASES:
PMID: 36250618 Hebert et al., 2022
Patient 1 - severe combined immunodeficiency (SCID), ectodermal dysplasia, alopecia, hypodontia and anonychia; het de novo PSMB10 NM_002801.3: c.601G>A p.(Gly201Arg) variant.

PMID: 38503300 van der Made et al., 2024
Identified de novo PSMB10 mutations in 6 infants with SCID-Omenn syndrome. The syndromic presentation includes severe combined immunodeficiency (SCID), as well as diarrhea (6/6), alopecia (4/5), and desquamating erythematous rash (6/6). Reported variants: PSMB10: c.166G>C, p.Asp56His and c.601G>A/c.601G>C, p.Gly201Arg.

PMID: 39734035 Kuehn et al., 2025
Case report: white female with SCID, failure to thrive, diarrhea, and pruritic rash - symptom onset at 5-9 months. Trio WES identified a de novo PSMB10 variant in the proband: c.601G>A, p.Gly201Arg.

https://doi.org/10.70962/jhi.20250096 Fournier et al., 2025
Report of 3 patients with WES detected de novo heterozygous PSMB10 variants: c.614A>C p.Asp205Ala for PI and c.623C>T p.Ser208Phe for PII and PIII. Presentation: combined immunodeficiency (3/3), generalized erythroderma with desquamation (1/3), chronic diarrhea (2/3), severe liver disease (2/3).
Functional evidence: PSMB10 constructs were expressed in HEK293T cells prior to SDS-PAGE/western blotting analysis. The p.Asp205Ala and p.Ser208Phe PSMB10 variants were shown to impair proteasome assembly and exert dominant-negative effects on PSMB9 expression.

BIALLELIC CASES:
PMID: 31783057 Sarrabay et al., 2020
3yo girl with a proteasome-associated autoinflammatory syndrome, homozygous for a PSMB10 c.41T>C, p.Phe14Ser variant. She presented with failure to thrive, cutaneous rash, and hepatosplenomegaly. No immunodeficiency.

PMID: 37600812 Papendorf et al., 2023
Three unrelated Brazilian patients present with four novel PSMB10 variants. All share the p.Phe14del variant plus a different novel variant: p.Gly167Asp, p.Cys83Leufs*123, and c.710+1G>C. All 3 patients had skin lesions, recurrent fevers, failure to thrive; microcytic anemia ascertained in 2/3.

PSMB10 is now associated with AD Immunodeficiency 121 with autoinflammation, MIM:620807 & AR Proteasome-associated autoinflammatory syndrome 5, MIM:619175 (OMIM accessed 10th Mar 2026).
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v8.88 PSMB10 Ida Ertmanska changed review comment from: Comment on mode of inheritance: There are now more than 3 cases reported with both mono- and bi- allelic PSMB10 variants - presenting with a proteasome-associated autoinflammatory syndrome (with or without recurrent infections and chronic diarrhea). Hence, the MOI should be updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal.; to: Comment on mode of inheritance: There are now more than 3 cases reported with both mono- and bi- allelic PSMB10 variants - presenting with a proteasome-associated autoinflammatory syndrome (with or without recurrent infections and chronic diarrhea). Hence, the MOI should be updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal.
Ectodermal dysplasia v4.27 PSMB10 Ida Ertmanska Classified gene: PSMB10 as Red List (low evidence)
Ectodermal dysplasia v4.27 PSMB10 Ida Ertmanska Gene: psmb10 has been classified as Red List (Low Evidence).
Ectodermal dysplasia v4.26 PSMB10 Ida Ertmanska Tag Q1_26_promote_green was removed from gene: PSMB10.
Ectodermal dysplasia v4.26 PSMB10 Ida Ertmanska changed review comment from: Comment on list classification: Monoallelic variants in PSMB10 have been reported to cause ectodermal dysplasia (alopecia, hypodontia, anonychia) in at least 5 unrelated individuals. Biallelic PSMB10 variants have not been linked to ectodermal dysplasia. Hence, the gene should be promoted to Green at the next update, with MOI MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted.; to: Comment on list classification: Monoallelic variants in PSMB10 have been reported to cause ectodermal dysplasia (alopecia, hypodontia, anonychia) in at least 5 unrelated individuals. However, inclusion criteria for this panel state at least two structures need to be affected (alopecia only is not sufficient. Biallelic PSMB10 variants have not been linked to ectodermal dysplasia. Hence, the gene can only be rated Red with current evidence, as only 1 case meets inclusion criteria (PMID: 36250618).
Ectodermal dysplasia v4.26 PSMB10 Ida Ertmanska edited their review of gene: PSMB10: Changed rating: RED
Primary lymphoedema v4.23 PLXNB2 Ida Ertmanska Tag watchlist tag was added to gene: PLXNB2.
Primary lymphoedema v4.23 PLXNB2 Ida Ertmanska Phenotypes for gene: PLXNB2 were changed from amelogenesis imperfecta; hearing loss; intellectual disability; lymphoedema to amelogenesis imperfecta, MONDO:0019507; sensorineural hearing loss disorder, MONDO:0020678; intellectual disability, MONDO:0001071
Primary lymphoedema v4.22 PLXNB2 Ida Ertmanska Classified gene: PLXNB2 as Amber List (moderate evidence)
Primary lymphoedema v4.22 PLXNB2 Ida Ertmanska Added comment: Comment on list classification: There are 3 individuals reported in literature with biallelic PLXNB2 variants and primary lymphoedema. Hence, this gene can only be rated Amber with the current evidence.
Primary lymphoedema v4.22 PLXNB2 Ida Ertmanska Gene: plxnb2 has been classified as Amber List (Moderate Evidence).
Primary lymphoedema v4.21 PLXNB2 Ida Ertmanska reviewed gene: PLXNB2: Rating: AMBER; Mode of pathogenicity: None; Publications: 38458752; Phenotypes: amelogenesis imperfecta, MONDO:0019507, sensorineural hearing loss disorder, MONDO:0020678, intellectual disability, MONDO:0001071; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic diabetes v3.17 APPL1 Arina Puzriakova Tag Q1_26_NHS_review tag was added to gene: APPL1.
Ectodermal dysplasia v4.26 PSMB10 Arina Puzriakova Phenotypes for gene: PSMB10 were changed from Immunodeficiency 121 with autoinflammation, OMIM:620807; Proteasome-associated autoinflammatory syndrome 5, OMIM:619175 to Immunodeficiency 121 with autoinflammation, OMIM:620807
Monogenic hearing loss v5.61 SLC19A2 Ida Ertmanska Classified gene: SLC19A2 as Amber List (moderate evidence)
Monogenic hearing loss v5.61 SLC19A2 Ida Ertmanska Added comment: Comment on list classification: There are numerous patients reported with Thiamine-Responsive Megaloblastic Anemia (TRMA) syndrome, caused by biallelic variants in the SLC19A2 gene, which typically presents with a triad of megaloblastic anemia, diabetes mellitus, and sensorineural hearing loss. Hearing loss can be the main presenting feature. Hence, this gene should be promoted to Green for monogenic hearing loss, with MOI set to BIALLELIC, autosomal or pseudoautosomal.
Monogenic hearing loss v5.61 SLC19A2 Ida Ertmanska Gene: slc19a2 has been classified as Amber List (Moderate Evidence).
Monogenic hearing loss v5.60 SLC19A2 Ida Ertmanska Phenotypes for gene: SLC19A2 were changed from Thiamine-responsive megaloblastic anemia syndrome, OMIM:249270 to Thiamine-responsive megaloblastic anemia syndrome, OMIM:249270; thiamine-responsive megaloblastic anemia syndrome, MONDO:0009575
Monogenic hearing loss v5.59 SLC19A2 Ida Ertmanska Tag Q1_26_promote_green tag was added to gene: SLC19A2.
Monogenic hearing loss v5.59 SLC19A2 Ida Ertmanska Phenotypes for gene: SLC19A2 were changed from to Thiamine-responsive megaloblastic anemia syndrome, OMIM:249270
Monogenic hearing loss v5.58 SLC19A2 Ida Ertmanska Publications for gene: SLC19A2 were set to
Monogenic hearing loss v5.57 SLC19A2 Ida Ertmanska reviewed gene: SLC19A2: Rating: GREEN; Mode of pathogenicity: None; Publications: 38037112, 40220483; Phenotypes: Thiamine-responsive megaloblastic anemia syndrome, OMIM:249270; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic diabetes v3.17 SLC19A2 Ida Ertmanska Phenotypes for gene: SLC19A2 were changed from Thiamine-responsive megaloblastic anemia syndrome; MEGALOBLASTIC ANEMIA, THIAMINE-RESPONSIVE, WITH DIABETES MELLITUS AND SENSORINEURAL DEAFNESS ROGERS SYNDROME to Thiamine-responsive megaloblastic anemia syndrome, OMIM:249270; diabetes mellitus, MONDO:0005015
Monogenic diabetes v3.16 SLC19A2 Ida Ertmanska Publications for gene: SLC19A2 were set to 26549656; 26839896
Monogenic diabetes v3.15 SLC19A2 Ida Ertmanska Tag curated_removed was removed from gene: SLC19A2.
Tag Q1_26_promote_green tag was added to gene: SLC19A2.
Tag Q1_26_NHS_review tag was added to gene: SLC19A2.
Monogenic diabetes v3.15 SLC19A2 Ida Ertmanska Classified gene: SLC19A2 as Amber List (moderate evidence)
Monogenic diabetes v3.15 SLC19A2 Ida Ertmanska Added comment: Comment on list classification: As reviewed by Kevin Colclough, patients with biallelic SLC19A2 variants are often diagnosed with diabetes after 9 months of age, which is in scope of this panel. Hence, SLC19A2 should be promoted to Green for Monogenic diabetes at the next update, with MOI set to BIALLELIC, autosomal or pseudoautosomal.
Monogenic diabetes v3.15 SLC19A2 Ida Ertmanska Gene: slc19a2 has been classified as Amber List (Moderate Evidence).
Monogenic diabetes v3.14 SLC19A2 Ida Ertmanska reviewed gene: SLC19A2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Thiamine-responsive megaloblastic anemia syndrome, OMIM:249270, diabetes mellitus, MONDO:0005015; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v6.184 FGFR1 Ida Ertmanska commented on gene: FGFR1: Comment on mode of inheritance: There are more than 3 individuals reported with biallelic FGFR1 variants and Hypogonadotropic hypogonadism. Individuals consistently presented with ectrodactyly, CC agenesis, and holoprosencephaly - disease features relevant to Fetal anomalies, as these would be detected on a prenatal scan. Hence, MOI should be changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal at the next update.
Fetal anomalies v6.184 FGFR1 Ida Ertmanska Phenotypes for gene: FGFR1 were changed from IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; OSTEOGLOPHONIC DYSPLASIA; PFEIFFER SYNDROME; KALLMANN SYNDROME TYPE 2; Hartsfield syndrome; Encephalocraniocutaneous lipomatosis to Hypogonadotropic hypogonadism 2 with or without anosmia, OMIM:147950; Hartsfield syndrome, OMIM:615465
Fetal anomalies v6.183 FGFR1 Ida Ertmanska Tag Q1_26_MOI tag was added to gene: FGFR1.
Fetal anomalies v6.183 FGFR1 Ida Ertmanska changed review comment from: PMID: 27055092 Mazen et al., 2016
Male patient with congenital heart disease (CHD) and ambiguous genitalia, referred at 15 months. Consanguineous parents, positive family history for CHD. Trio WES revealed a homozygous FGFR1 c.1418G>A variant (hg38: c.1424G>A, p.Arg475Gln - rs747333248, 34 total alleles in gnomAD v4.1.0, no homozygotes). Patient also homozygous for a STARD3 p.Ala247Val mutation, no disease association reported for this gene. Ambiguous genitalia highlighted as unusual presentation in FGFR1-related disease.

PMID: 25394172 Villanueva et al., 2015
7 individuals with Congenital hypogonadotropic hypogonadism (CHH), 3/7 with anosmia, and 7/7 with split hand/foot malformation. The patients harboured FGFR1 variants - 6 heterozygous and 1 homozygous.
P1: male, homozygous for c.1286T>A, p.V429E. Heterozygous sister and parents. Sister has hyposmia, otherwise no phenotype reported in heterozygous family members.
In the 6 heterozygous pedigrees, CHH was an autosomal dominant trait with incomplete penetrance.

PMID: 23812909 Simonis et al., 2013
6 patients with Hartsfield syndrome and 1 female fetus with similar symptoms. FGFR1 variants were detected in the extracellular binding domain (two patients with homozygous mutations) or the intracellular tyrosine kinase domain (four heterozygous de novo variants). Patients presented with holoprosencephaly 7/7 (lobar, alobar, or semilobar), corpus callosum agenesis 5/7 (full or partial), ectrodactyly 7/7 (hands and/or feet affected), growth retardation 6/6, genital anomalies 3/6 (micropenis, cryptorchidism), DD/ID 6/6 (mild to severe). P1 was homozygous for L165S, heterozygous parents unaffected. P2 was homozygous for L191S, parents not available for testing.

PMID: 23154428 Jarzabek et al., 2012
5 Kallmann syndrome (KS) patients who carry FGFR1 mutations (Gly270Asp, Gly97Ser, Met161Thr, Ser685Phe and Ala167Ser/Ala167Ser). Patients 1-4 harboured de novo heterozygous FGFR1 mutations, while P5 was homozygous for the c.499G>T, p.Ala167Ser variant - his parents are sister are heterozygous and unaffected. All 5 patients had absent puberty, as well as hyposmia or anosmia. 3/5 patients presented with skeletal abnormalities and lip/palate malformations.
P5 (previously described in PMID: 12627230) had KS, cleft palate, corpus callosum agenesis, vertebral anomalies, unilateral fusion of fourth and fifth metacarpal bones, and bilateral oligodactyly of feet (four digits).

FGFR1 is associated with multiple dominant conditions in OMIM, including AD Hypogonadotropic hypogonadism 2 with or without anosmia, OMIM:147950 and AD Hartsfield syndrome, OMIM:615465 (accessed 27th Feb 2026).; to: PMID: 27055092 Mazen et al., 2016
Male patient with congenital heart disease (CHD) and ambiguous genitalia, referred at 15 months. Consanguineous parents, positive family history for CHD. Trio WES revealed a homozygous FGFR1 c.1418G>A variant (hg38: c.1424G>A, p.Arg475Gln - rs747333248, 34 total alleles in gnomAD v4.1.0, no homozygotes). Patient also homozygous for a STARD3 p.Ala247Val mutation, no disease association reported for this gene. Ambiguous genitalia highlighted as unusual presentation in FGFR1-related disease.

PMID: 25394172 Villanueva et al., 2015
7 individuals with Congenital hypogonadotropic hypogonadism (CHH), 3/7 with anosmia, and 7/7 with split hand/foot malformation. The patients harboured FGFR1 variants - 6 heterozygous and 1 homozygous.
P1: male, homozygous for c.1286T>A, p.V429E. Heterozygous sister and parents. Sister has hyposmia, otherwise no phenotype reported in heterozygous family members.
In the 6 heterozygous pedigrees, CHH was an autosomal dominant trait with incomplete penetrance.

PMID: 23812909 Simonis et al., 2013
6 patients with Hartsfield syndrome and 1 female fetus with similar symptoms. FGFR1 variants were detected in the extracellular binding domain (two patients with homozygous mutations) or the intracellular tyrosine kinase domain (four heterozygous de novo variants). Patients presented with holoprosencephaly 7/7 (lobar, alobar, or semilobar), corpus callosum agenesis 5/7 (full or partial), ectrodactyly 7/7 (hands and/or feet affected), growth retardation 6/6, genital anomalies 3/6 (micropenis, cryptorchidism), DD/ID 6/6 (mild to severe). Fetal case (patient 7) had no FGFR1 mutation detected.


PMID: 23154428 Jarzabek et al., 2012
5 Kallmann syndrome (KS) patients who carry FGFR1 mutations (Gly270Asp, Gly97Ser, Met161Thr, Ser685Phe and Ala167Ser/Ala167Ser). Patients 1-4 harboured de novo heterozygous FGFR1 mutations, while P5 was homozygous for the c.499G>T, p.Ala167Ser variant - his parents are sister are heterozygous and unaffected. All 5 patients had absent puberty, as well as hyposmia or anosmia. 3/5 patients presented with skeletal abnormalities and lip/palate malformations.
P5 (previously described in PMID: 12627230) had KS, cleft palate, corpus callosum agenesis, vertebral anomalies, unilateral fusion of fourth and fifth metacarpal bones, and bilateral oligodactyly of feet (four digits).

FGFR1 is associated with multiple dominant conditions in OMIM, including AD Hypogonadotropic hypogonadism 2 with or without anosmia, OMIM:147950 and AD Hartsfield syndrome, OMIM:615465 (accessed 27th Feb 2026).
Fetal anomalies v6.183 FGFR1 Ida Ertmanska reviewed gene: FGFR1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23154428, 23812909, 25394172, 27055092; Phenotypes: Hypogonadotropic hypogonadism 2 with or without anosmia, OMIM:147950, Hartsfield syndrome, OMIM:615465; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Differences in sex development v4.17 FGFR1 Ida Ertmanska Phenotypes for gene: FGFR1 were changed from Hypogonadotropic hypogonadism 2 with out without anosmia to Hypogonadotropic hypogonadism 2 with or without anosmia, OMIM:147950; Hartsfield syndrome, OMIM:615465
Differences in sex development v4.16 FGFR1 Ida Ertmanska Publications for gene: FGFR1 were set to (PMID: 41108094; 34589657; 32853167)
Differences in sex development v4.15 FGFR1 Ida Ertmanska Classified gene: FGFR1 as Red List (low evidence)
Differences in sex development v4.15 FGFR1 Ida Ertmanska Added comment: Comment on list classification: There is only one individual reported in literature with a biallelic FGFR1 variant and a diagnosed difference in sex development (ambiguous genitalia - PMID: 27055092). Other reported cases are more aligned with diagnosis of Hypogonadotropic hypogonadism (FGFR1 is already Green on that panel). Hence, this gene can only be rated Red on Differences in sex development given the evidence available.
Differences in sex development v4.15 FGFR1 Ida Ertmanska Gene: fgfr1 has been classified as Red List (Low Evidence).
Differences in sex development v4.14 FGFR1 Ida Ertmanska edited their review of gene: FGFR1: Changed rating: RED; Changed publications to: 23154428, 23812909, 25394172, 27055092, 32853167, 34589657, 41108094; Changed phenotypes to: Hypogonadotropic hypogonadism 2 with or without anosmia, OMIM:147950, Hartsfield syndrome, OMIM:615465
Differences in sex development v4.14 FGFR1 Ida Ertmanska commented on gene: FGFR1
Optic neuropathy v5.52 INTS11 Ida Ertmanska Classified gene: INTS11 as Amber List (moderate evidence)
Optic neuropathy v5.52 INTS11 Ida Ertmanska Added comment: Comment on list classification: There are 5 individuals from 4 families reported with biallelic INTS11 variants and optic atrophy. Hence, this gene should be promoted to Green at the next update, with MOI set to BIALLELIC, autosomal or pseudoautosomal.
Optic neuropathy v5.52 INTS11 Ida Ertmanska Gene: ints11 has been classified as Amber List (Moderate Evidence).
Retinal disorders v8.103 INTS11 Ida Ertmanska Phenotypes for gene: INTS11 were changed from Retinal dystrophy to Neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities, OMIM:620428
Retinal disorders v8.102 INTS11 Ida Ertmanska Publications for gene: INTS11 were set to PMID: 41810893
Optic neuropathy v5.51 INTS11 Ida Ertmanska gene: INTS11 was added
gene: INTS11 was added to Optic neuropathy. Sources: Literature
Q1_26_promote_green tags were added to gene: INTS11.
Mode of inheritance for gene: INTS11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS11 were set to 37054711; 41810893
Phenotypes for gene: INTS11 were set to Neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities, OMIM:620428
Review for gene: INTS11 was set to GREEN
Added comment: PMID: 41810893 Lin et al., 2026
Report of four affected individuals with biallelic INTS11 variants from two unrelated families.
Retinal phenotype: mild optic disc pallor; severe thinning of the inner retinal layers with preserved outer retinal layers, generalized rod and cone system dysfunction localized to the inner retina or post-phototransduction.
Individuals A-1 and A-2 were compound heterozygous for missense INTS11 variants c.34G > A; p.(Gly12Ser) and c.1219C > T; p.(Pro407Ser), as previously described. Novel compound het INTS11 variants (c.721G > A, p.(Ala241Thr) and c.983T > A, p.(Leu328Gln)) were identified in individuals B-3 and B-4.

PMID: 37054711 Tepe et al., 2023
15 individuals from 10 unrelated families with bi-allelic variants in INTS11 who present with global developmental and language delay, intellectual disability, impaired motor development, and brain atrophy. 5 patients were noted to have optic atrophy, and 2 had retinal dystrophy. Less specific ocular findings included myopia, astigmatism, and strabismus.
Sources: Literature
Retinal disorders v8.101 INTS11 Ida Ertmanska Tag Q1_26_promote_green tag was added to gene: INTS11.
Tag Q1_26_NHS_review tag was added to gene: INTS11.
Retinal disorders v8.101 INTS11 Ida Ertmanska Classified gene: INTS11 as Amber List (moderate evidence)
Retinal disorders v8.101 INTS11 Ida Ertmanska Added comment: Comment on list classification: There are at least 3 unrelated families with individuals harbouring biallelic INTS11 variants affected by retinal disease. Hence, this gene should be updated to Green at the next update, with MOI set to BIALLELIC, autosomal or pseudoautosomal.
Retinal disorders v8.101 INTS11 Ida Ertmanska Gene: ints11 has been classified as Amber List (Moderate Evidence).
Retinal disorders v8.100 INTS11 Ida Ertmanska changed review comment from: PMID: 41810893 Lin et al., 2026
Report of four affected individuals with biallelic INTS11 variants from two unrelated families.
Retinal phenotype: mild optic disc pallor; severe thinning of the inner retinal layers with preserved outer retinal layers, generalized rod and cone system dysfunction localized to the inner retina or post-phototransduction.
Individuals A-1 and A-2 were compound heterozygous for missense INTS11 variants c.34G > A; p.(Gly12Ser) and c.1219C > T; p.(Pro407Ser), as previously described. Novel compound het INTS11 variants (c.721G > A, p.(Ala241Thr) and c.983T > A, p.(Leu328Gln)) were identified in individuals B-3 and B-4.

PMID: 37054711 Tepe et al., 2023
15 individuals from 10 unrelated families with bi-allelic variants in INTS11 who present with global developmental and language delay, intellectual disability, impaired motor development, and brain atrophy. 5 patients were noted to have optic atrophy, and 2 had retinal dystrophy.; to: PMID: 41810893 Lin et al., 2026
Report of four affected individuals with biallelic INTS11 variants from two unrelated families.
Retinal phenotype: mild optic disc pallor; severe thinning of the inner retinal layers with preserved outer retinal layers, generalized rod and cone system dysfunction localized to the inner retina or post-phototransduction.
Individuals A-1 and A-2 were compound heterozygous for missense INTS11 variants c.34G > A; p.(Gly12Ser) and c.1219C > T; p.(Pro407Ser), as previously described. Novel compound het INTS11 variants (c.721G > A, p.(Ala241Thr) and c.983T > A, p.(Leu328Gln)) were identified in individuals B-3 and B-4.

PMID: 37054711 Tepe et al., 2023
15 individuals from 10 unrelated families with bi-allelic variants in INTS11 who present with global developmental and language delay, intellectual disability, impaired motor development, and brain atrophy. 5 patients were noted to have optic atrophy, and 2 had retinal dystrophy. Less specific ocular findings included myopia, astigmatism, and strabismus.
Retinal disorders v8.100 INTS11 Ida Ertmanska reviewed gene: INTS11: Rating: GREEN; Mode of pathogenicity: None; Publications: 37054711, 41810893; Phenotypes: Neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities, OMIM:620428; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Optic neuropathy v5.50 FSD1L Ida Ertmanska Classified gene: FSD1L as Amber List (moderate evidence)
Optic neuropathy v5.50 FSD1L Ida Ertmanska Added comment: Comment on list classification: There are 3 unrelated families reported in literature with biallelic FSD1L variants and optic nerve atrophy/hypoplasia. Hence, this gene can be promoted to Green at the next update, with MOI set to BIALLELIC, autosomal or pseudoautosomal.
Optic neuropathy v5.50 FSD1L Ida Ertmanska Gene: fsd1l has been classified as Amber List (Moderate Evidence).
Optic neuropathy v5.49 FSD1L Ida Ertmanska gene: FSD1L was added
gene: FSD1L was added to Optic neuropathy. Sources: Literature
Q1_26_promote_green tags were added to gene: FSD1L.
Mode of inheritance for gene: FSD1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FSD1L were set to 41720098; 41720099
Phenotypes for gene: FSD1L were set to neurodevelopmental disorder, MONDO:0700092
Review for gene: FSD1L was set to GREEN
Added comment: PMID: 41720098 Serpieri et al., 2026
Report of eleven individuals (including five fetuses) from six unrelated families harbouring biallelic FSD1L variants. Seq method: exome sequencing. Consanguinity was confirmed in 4/6 families, and suspected in the fifth.
Phenotype spectrum: severe intellectual disability (5/5 assessed from 3 families), epilepsy (5 individuals from 3 families), severe hydrocephalus (3 families), vision deficit due to optic nerve hypoplasia/atrophy (3 families), spastic tetraparesis (2 families) corpus callosum hypoplasia/agenesis on MRI (5/5 families assessed),

Variants detected - largely nonsense type:
Family A - homozygous c.409T>G (p.Leu137Val);
Family B - 3 affected fetuses homozygous for c.1411C>T (p.Gln471Ter);
Family C - sibs compound het for c.1228T>G (p.Phe410Val) and c.1251_1252insTAA (p.Thr418Ter);
Family D - affected individuals (1 fetal case) homozygous for c.1366G>C (p.Asp456His) - shown to impact splicing (r.406_442del), resulting in predicted p.Ser136LeufsTer19 change;
Family E - affected child with homozygous c.835C>T (p.Arg279Ter) change;
Family F - fetus homozygous for c.1260G>A (p.Trp420Ter);

Functional evidence: Fsd1l depletion in mouse embryos recapitulated the ventricular dilation observed in affected fetuses.

PMID 41720099 Lin et al., 2026
Report of 6 affected individuals from 4 families with retinitis pigmentosa. One individual underwent a full neurological evaluation, including brain neuroimaging, which revealed no evidence of central nervous system involvement.
FSD1L variants detected:
Family A: 2 sibs compound het for c.1049G>A (p.Arg350Gln) and c.1428del (p.Phe476Leufs∗22)
Family B: individual comp het for c.488G>A (p.Arg163His), c.488G>A & c.745C>T (p.Arg249∗)
Family C: 2 sibs compound het for c.488G>A (p.Arg163His) & c.226_227del (p.Ser77Argfs∗4)
Family D: individual compound het for c.1037_1038delinsT (p.Pro346Leufs∗8) and c.1025+624_1025+649del
Sibs from family A had mild neurological involvement (mild ID, spastic diplegia in one sibling).
Authors note that "specific combination and functional severity of the two alleles likely determines the clinical outcome", with non-LoF variants causing a milder effect (e.g., isolated retinal phenotype).

FSD1L is not yet associated with a phenotype in OMIM or Gene2Phenotype.
Sources: Literature
Fetal anomalies v6.183 FSD1L Ida Ertmanska Tag Q1_26_promote_green tag was added to gene: FSD1L.
Fetal anomalies v6.183 FSD1L Ida Ertmanska Classified gene: FSD1L as Amber List (moderate evidence)
Fetal anomalies v6.183 FSD1L Ida Ertmanska Added comment: Comment on list classification: There are at least three unrelated fetal cases reported in literature with biallelic FSD1L variants. Based on available evidence, FSD1L should be promoted to Green at the next update.
Fetal anomalies v6.183 FSD1L Ida Ertmanska Gene: fsd1l has been classified as Amber List (Moderate Evidence).
Autoinflammatory disorders v2.37 PTPN1 Ida Ertmanska changed review comment from: Comment on list classification: There are 11 unrelated individuals reported with heterozygous PTPN1 variants, presenting in childhood with loss of previously acquired skills, spasticity/dystonia, cerebral atrophy, and white matter changes. Several patients responded well to immune suppression treatment. There is a high degree of non-penetrance, as 9/12 reported patients have inherited the PTPN1 variants from their asymptomatic parents. Hence, this gene is recommended for Green with expert review to determine if the non-penetrance is in scope of testing.; to: Comment on list classification: There are 11 unrelated individuals reported with heterozygous PTPN1 variants, presenting in childhood with loss of previously acquired skills, spasticity/dystonia, cerebral atrophy, and white matter changes. Several patients responded well to immune suppression treatment. There is a high degree of non-penetrance, as 9/12 reported patients have inherited the PTPN1 variants from their asymptomatic parents. Hence, this gene is recommended for Green with expert review to determine if the non-penetrance is in scope of testing.
Autoinflammatory disorders v2.37 PTPN1 Ida Ertmanska changed review comment from: Comment on list classification: There are 11 unrelated individuals reported with heterozygous PTPN1 variants, presenting in childhood with loss of previously acquired skills, spasticity/dystonia, cerebral atrophy, and white matter changes. Several patients responded to immune suppression treatment. There is a high degree of non-penetrance, as 9/12 reported patients have inherited the PTPN1 variants from their asymptomatic parents. Hence, this gene is recommended for Green with expert review to determine if the non-penetrance is in scope of testing.; to: Comment on list classification: There are 11 unrelated individuals reported with heterozygous PTPN1 variants, presenting in childhood with loss of previously acquired skills, spasticity/dystonia, cerebral atrophy, and white matter changes. Several patients responded well to immune suppression treatment. There is a high degree of non-penetrance, as 9/12 reported patients have inherited the PTPN1 variants from their asymptomatic parents. Hence, this gene is recommended for Green with expert review to determine if the non-penetrance is in scope of testing.
Autoinflammatory disorders v2.37 PTPN1 Ida Ertmanska Classified gene: PTPN1 as Amber List (moderate evidence)
Autoinflammatory disorders v2.37 PTPN1 Ida Ertmanska Added comment: Comment on list classification: There are 11 unrelated individuals reported with heterozygous PTPN1 variants, presenting in childhood with loss of previously acquired skills, spasticity/dystonia, cerebral atrophy, and white matter changes. Several patients responded to immune suppression treatment. There is a high degree of non-penetrance, as 9/12 reported patients have inherited the PTPN1 variants from their asymptomatic parents. Hence, this gene is recommended for Green with expert review to determine if the non-penetrance is in scope of testing.
Autoinflammatory disorders v2.37 PTPN1 Ida Ertmanska Gene: ptpn1 has been classified as Amber List (Moderate Evidence).
Autoinflammatory disorders v2.36 PTPN1 Ida Ertmanska gene: PTPN1 was added
gene: PTPN1 was added to Autoinflammatory disorders. Sources: Literature
Q1_26_promote_green, Q1_26_expert_review tags were added to gene: PTPN1.
Mode of inheritance for gene: PTPN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTPN1 were set to 10066179; 39986310
Phenotypes for gene: PTPN1 were set to Encephalopathy, HP:0001298; dystonia, early-onset, and/or spastic paraplegia, MONDO:0859215
Review for gene: PTPN1 was set to GREEN
Added comment: PMID: 39986310 Zhu et al., 2025
Reported heterozygous PTPN1 variants in 12 patients from 11 families. 2/10 were canonical splice variants, 2 were missense variants, and 6 were STOP-gain. 3 cases were de novo, 9 individuals inherited the variant from an asymptomatic parent. Sequencing method: WES + Sanger.

Phenotype: 12/12 individuals experienced subacute loss of skills (age range 15 months to 8 years) after initial normal development in 11 of 12 (one patient had mild motor delay); weakness (12/12), spasticity (initially manifesting as a hemiparesis in seven patients and then becoming bilateral) +/- dystonia, bulbar involvement (dysphagia and/or dysphasia) in 11/12 patients; absence of seizures. In 4/12 patients, fever and raised liver enzymes were noted around the time of presentation.

Brain MRI findings: Cerebral atrophy (9/12 patients), non-specific white matter changes (8/12), intracranial calcification (2/12). In 8 cases, the brain abnormalities resolved.Some patients demonstrated stabilisation / recovery of neurological function in the absence of treatment, while in others the disease appeared to respond to immune suppression.

Functional evidence: PMID: 10066179 Elchebly et al., 1999 - Ptpn1 knock-out (KO) mice are both viable and healthy, demonstrating enhanced insulin sensitivity and resistance to metabolic syndrome.

PTPN1 is associated with {Insulin resistance, susceptibility to}, MIM:1258539 in OMIM. It is not associated with disease in ClinGen or Gene2Phenotype (resources accessed 24 Mar 2026).
Probability of loss-of-function intolerance (pLI) score = 1.00 (predicted to be highly intolerant to LoF).
Sources: Literature
Ichthyosis and erythrokeratoderma v4.12 MPDU1 Ida Ertmanska Phenotypes for gene: MPDU1 were changed from Ichthyosis to Congenital disorder of glycosylation, type If, OMIM:609180; MPDU1-congenital disorder of glycosylation, MONDO:0012211; ichthyosis, MONDO:0019269
Ichthyosis and erythrokeratoderma v4.11 MPDU1 Ida Ertmanska Publications for gene: MPDU1 were set to 11733556
Ichthyosis and erythrokeratoderma v4.10 MPDU1 Ida Ertmanska Tag Q1_26_promote_green tag was added to gene: MPDU1.
Tag Q1_26_NHS_review tag was added to gene: MPDU1.
Ichthyosis and erythrokeratoderma v4.10 MPDU1 Ida Ertmanska Classified gene: MPDU1 as Amber List (moderate evidence)
Ichthyosis and erythrokeratoderma v4.10 MPDU1 Ida Ertmanska Added comment: Comment on list classification: There are more than 3 unrelated individuals reported in literature with biallelic MPDU1 variants and syndromic ichthyosis / erythrokeratoderma. Hence, this gene should be promoted to Green at the next update, with MOI set to BIALLELIC, autosomal or pseudoautosomal.
Ichthyosis and erythrokeratoderma v4.10 MPDU1 Ida Ertmanska Gene: mpdu1 has been classified as Amber List (Moderate Evidence).
Ichthyosis and erythrokeratoderma v4.9 MPDU1 Ida Ertmanska reviewed gene: MPDU1: Rating: GREEN; Mode of pathogenicity: None; Publications: 11733564, 29721919, 35279850, 36755425, 38831602; Phenotypes: Congenital disorder of glycosylation, type If, OMIM:609180; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paroxysmal central nervous system disorders v4.3 RHOBTB2 Ida Ertmanska Publications for gene: RHOBTB2 were set to 33504645
Paroxysmal central nervous system disorders v4.2 RHOBTB2 Ida Ertmanska Tag Q1_26_MOI tag was added to gene: RHOBTB2.
Paroxysmal central nervous system disorders v4.2 RHOBTB2 Ida Ertmanska commented on gene: RHOBTB2: As there are now more than 3 individuals reported with both mono- and bi-allelic variants in RHOBTB2 with movement disorders, the mode of inheritance should be changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal at the next update.
Intellectual disability v9.353 RHOBTB2 Ida Ertmanska changed review comment from: As there are now more than 3 individuals reported with both mono- and bi-allelic variants in RHOBTB2 with epilepsy, the mode of inheritance should be changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal at the next update.; to: As there are now more than 3 individuals reported with both mono- and bi-allelic variants in RHOBTB2 with syndromic ID/DD, the mode of inheritance should be changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal at the next update.
Paroxysmal central nervous system disorders v4.2 RHOBTB2 Ida Ertmanska reviewed gene: RHOBTB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37165955; Phenotypes: Developmental and epileptic encephalopathy 64, OMIM:618004, developmental and epileptic encephalopathy, 64, MONDO:0033373; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v9.353 RHOBTB2 Ida Ertmanska Publications for gene: RHOBTB2 were set to 29276004; 29768694; 26740508
Intellectual disability v9.352 RHOBTB2 Ida Ertmanska Phenotypes for gene: RHOBTB2 were changed from Epileptic encephalopathy, early infantile, 64, 618004; Global developmental delay; Intellectual disability; Seizures; Postnatal microcephaly to Developmental and epileptic encephalopathy 64, OMIM:618004; developmental and epileptic encephalopathy, 64, MONDO:0033373
Intellectual disability v9.351 RHOBTB2 Ida Ertmanska changed review comment from: PMID: 37165955 Langhammer et al., 2023
Report of 13 individuals from 9 families with bilallelic loss of function RHOBTB2 variants with a variable neurodevelopmental disorder including intellectual disability and seizures. 7/9 families were confirmed as consanguineous. Phenotypic spectrum: DD/ID ranging from learning difficulties to moderate ID (11/13 individuals), epilepsy, seizures, and/or abnormal EEG (11/13), microcephaly (5/9 individuals assessed, 2 with more than -3 SD), ataxia & gait disturbances (7/13), MRI anomalies seen in 2 patients. Study also reported 6 new cases with de novo heterozygous missense variants in RHOBTB2.; to: PMID: 37165955 Langhammer et al., 2023
Report of 13 individuals from 9 families with bilallelic loss of function RHOBTB2 variants with a variable neurodevelopmental disorder including intellectual disability and seizures. 7/9 families were confirmed as consanguineous. Phenotypic spectrum: DD/ID ranging from learning difficulties to moderate ID (11/13 individuals), epilepsy, seizures, and/or abnormal EEG (11/13), microcephaly (5/9 individuals assessed, 2 with more than -3 SD), ataxia & gait disturbances (8/10), MRI anomalies seen in 2 patients. Study also reported 6 new cases with de novo heterozygous missense variants in RHOBTB2.
Early onset or syndromic epilepsy v8.170 RHOBTB2 Ida Ertmanska changed review comment from: PMID: 37165955 Langhammer et al., 2023
Report of 13 individuals from 9 families with bilallelic loss of function RHOBTB2 variants with a variable neurodevelopmental disorder including intellectual disability and seizures. 7/9 families were confirmed as consanguineous. Phenotypic spectrum: DD/ID ranging from learning difficulties to moderate ID (11/13 individuals), epilepsy, seizures, and/or abnormal EEG (11/13), microcephaly (5/9 individuals assessed, 2 with more than -3 SD), ataxia & gait disturbances (7/13), MRI anomalies seen in 2 patients. Study also reported 6 new cases with de novo heterozygous missense variants in RHOBTB2.; to: PMID: 37165955 Langhammer et al., 2023
Report of 13 individuals from 9 families with bilallelic loss of function RHOBTB2 variants with a variable neurodevelopmental disorder including intellectual disability and seizures. 7/9 families were confirmed as consanguineous. Phenotypic spectrum: DD/ID ranging from learning difficulties to moderate ID (11/13 individuals), epilepsy, seizures, and/or abnormal EEG (11/13), microcephaly (5/9 individuals assessed, 2 with more than -3 SD), ataxia & gait disturbances (8/10), MRI anomalies seen in 2 patients. Study also reported 6 new cases with de novo heterozygous missense variants in RHOBTB2.
Intellectual disability v9.351 RHOBTB2 Ida Ertmanska Tag Q1_26_MOI tag was added to gene: RHOBTB2.
Early onset or syndromic epilepsy v8.170 RHOBTB2 Ida Ertmanska changed review comment from: PMID: 37165955 Langhammer et al., 2023
Report of 13 individuals from 9 families with bilallelic loss of function variants with a variable neurodevelopmental disorder including intellectual disability and seizures. 7/9 families were confirmed as consanguineous. Phenotypic spectrum: DD/ID ranging from learning difficulties to moderate ID (11/13 individuals), epilepsy, seizures, and/or abnormal EEG (11/13), microcephaly (5/9 individuals assessed, 2 with more than -3 SD), ataxia & gait disturbances (7/13), MRI anomalies seen in 2 patients. Study also reported 6 new cases with de novo heterozygous missense variants.; to: PMID: 37165955 Langhammer et al., 2023
Report of 13 individuals from 9 families with bilallelic loss of function RHOBTB2 variants with a variable neurodevelopmental disorder including intellectual disability and seizures. 7/9 families were confirmed as consanguineous. Phenotypic spectrum: DD/ID ranging from learning difficulties to moderate ID (11/13 individuals), epilepsy, seizures, and/or abnormal EEG (11/13), microcephaly (5/9 individuals assessed, 2 with more than -3 SD), ataxia & gait disturbances (7/13), MRI anomalies seen in 2 patients. Study also reported 6 new cases with de novo heterozygous missense variants in RHOBTB2.
Intellectual disability v9.351 RHOBTB2 Ida Ertmanska changed review comment from: PMID: 37165955 Langhammer et al., 2023
Report of 13 individuals from 9 families with bilallelic loss of function variants with a variable neurodevelopmental disorder including intellectual disability and seizures. 7/9 families were confirmed as consanguineous. Phenotypic spectrum: DD/ID ranging from learning difficulties to moderate ID (11/13 individuals), epilepsy, seizures, and/or abnormal EEG (11/13), microcephaly (5/9 individuals assessed, 2 with more than -3 SD), ataxia & gait disturbances (7/13), MRI anomalies seen in 2 patients. Study also reported 6 new cases with de novo heterozygous missense variants.; to: PMID: 37165955 Langhammer et al., 2023
Report of 13 individuals from 9 families with bilallelic loss of function RHOBTB2 variants with a variable neurodevelopmental disorder including intellectual disability and seizures. 7/9 families were confirmed as consanguineous. Phenotypic spectrum: DD/ID ranging from learning difficulties to moderate ID (11/13 individuals), epilepsy, seizures, and/or abnormal EEG (11/13), microcephaly (5/9 individuals assessed, 2 with more than -3 SD), ataxia & gait disturbances (7/13), MRI anomalies seen in 2 patients. Study also reported 6 new cases with de novo heterozygous missense variants in RHOBTB2.
Intellectual disability v9.351 RHOBTB2 Ida Ertmanska commented on gene: RHOBTB2: As there are now more than 3 individuals reported with both mono- and bi-allelic variants in RHOBTB2 with epilepsy, the mode of inheritance should be changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal at the next update.
Intellectual disability v9.351 RHOBTB2 Ida Ertmanska reviewed gene: RHOBTB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37165955; Phenotypes: Developmental and epileptic encephalopathy 64, OMIM:618004, developmental and epileptic encephalopathy, 64, MONDO:0033373; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v8.170 RHOBTB2 Ida Ertmanska edited their review of gene: RHOBTB2: Changed phenotypes to: Developmental and epileptic encephalopathy 64, OMIM:618004, developmental and epileptic encephalopathy, 64, MONDO:0033373
Early onset or syndromic epilepsy v8.170 RHOBTB2 Ida Ertmanska commented on gene: RHOBTB2: Comment on mode of inheritance: As there are now more than 3 individuals reported with both mono- and bi-allelic variants in RHOBTB2 with epilepsy, the mode of inheritance should be changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal at the next update.
Early onset or syndromic epilepsy v8.170 RHOBTB2 Ida Ertmanska Phenotypes for gene: RHOBTB2 were changed from Epileptic encephalopathy, early infantile, 64 618004 to Developmental and epileptic encephalopathy 64, OMIM:618004; developmental and epileptic encephalopathy, 64, MONDO:0033373
Early onset or syndromic epilepsy v8.169 RHOBTB2 Ida Ertmanska Publications for gene: RHOBTB2 were set to 29276004; 29768694; 26740508
Early onset or syndromic epilepsy v8.168 RHOBTB2 Ida Ertmanska Tag Q1_26_MOI tag was added to gene: RHOBTB2.
Early onset or syndromic epilepsy v8.168 RHOBTB2 Ida Ertmanska reviewed gene: RHOBTB2: Rating: GREEN; Mode of pathogenicity: None; Publications: 37165955; Phenotypes: Developmental and epileptic encephalopathy 64, OMIM:618004; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v6.182 PPP2R1A Arina Puzriakova Phenotypes for gene: PPP2R1A were changed from INTELLECTUAL DISABILITY to Houge-Janssens syndrome 2, OMIM:616362
Arthrogryposis v9.32 DDR2 Eleanor Williams Phenotypes for gene: DDR2 were changed from to Warburg-Cinotti syndrome, OMIM:618175
Childhood onset hereditary spastic paraplegia v8.44 PTPN1 Ida Ertmanska Classified gene: PTPN1 as Amber List (moderate evidence)
Childhood onset hereditary spastic paraplegia v8.44 PTPN1 Ida Ertmanska Added comment: Comment on list classification: There are 11 unrelated individuals reported with heterozygous PTPN1 variants, presenting in childhood with loss of previously acquired skills, spasticity/dystonia, cerebral atrophy, and white matter changes. There is a high degree of non-penetrance, as 9/12 reported patients have inherited the PTPN1 variants from their asymptomatic parents. Hence, this gene is recommended for Green with expert review to determine if the non-penetrance is in scope of testing.
Childhood onset hereditary spastic paraplegia v8.44 PTPN1 Ida Ertmanska Gene: ptpn1 has been classified as Amber List (Moderate Evidence).
Childhood onset hereditary spastic paraplegia v8.43 PTPN1 Ida Ertmanska gene: PTPN1 was added
gene: PTPN1 was added to Childhood onset hereditary spastic paraplegia. Sources: Literature
Q1_26_promote_green, Q1_26_expert_review tags were added to gene: PTPN1.
Mode of inheritance for gene: PTPN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTPN1 were set to 10066179; 39986310
Phenotypes for gene: PTPN1 were set to Encephalopathy, HP:0001298; dystonia, early-onset, and/or spastic paraplegia, MONDO:0859215
Review for gene: PTPN1 was set to GREEN
Added comment: PMID: 39986310 Zhu et al., 2025
Reported heterozygous PTPN1 variants in 12 patients from 11 families. 2/10 were canonical splice variants, 2 were missense variants, and 6 were STOP-gain. 3 cases were de novo, 9 individuals inherited the variant from an asymptomatic parent. Sequencing method: WES + Sanger.

Phenotype: 12/12 individuals experienced subacute loss of skills (age range 15 months to 8 years) after initial normal development in 11 of 12 (one patient had mild motor delay); weakness (12/12), spasticity (initially manifesting as a hemiparesis in seven patients and then becoming bilateral) +/- dystonia, bulbar involvement (dysphagia and/or dysphasia) in 11/12 patients; absence of seizures. In 4/12 patients, fever and raised liver enzymes were noted around the time of presentation.

Brain MRI findings: Cerebral atrophy (9/12 patients), non-specific white matter changes (8/12), intracranial calcification (2/12). In 8 cases, the brain abnormalities resolved.Some patients demonstrated stabilisation / recovery of neurological function in the absence of treatment, while in others the disease appeared to respond to immune suppression.

Functional evidence: PMID: 10066179 Elchebly et al., 1999 - Ptpn1 knock-out (KO) mice are both viable and healthy, demonstrating enhanced insulin sensitivity and resistance to metabolic syndrome.

PTPN1 is associated with {Insulin resistance, susceptibility to}, MIM:1258539 in OMIM. It is not associated with disease in ClinGen or Gene2Phenotype (resources accessed 24 Mar 2026).
Probability of loss-of-function intolerance (pLI) score = 1.00 (predicted to be highly intolerant to LoF).
Sources: Literature
Intellectual disability v9.351 PTPN1 Ida Ertmanska Tag Q1_26_expert_review tag was added to gene: PTPN1.
White matter disorders and cerebral calcification - narrow panel v7.24 PTPN1 Ida Ertmanska Tag Q1_26_expert_review tag was added to gene: PTPN1.
Childhood onset dystonia, chorea or related movement disorder v7.20 PTPN1 Ida Ertmanska Tag Q1_26_expert_review tag was added to gene: PTPN1.
Childhood onset dystonia, chorea or related movement disorder v7.20 PTPN1 Ida Ertmanska Classified gene: PTPN1 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v7.20 PTPN1 Ida Ertmanska Added comment: Comment on list classification: There are 11 unrelated individuals reported with heterozygous PTPN1 variants, presenting in childhood with loss of previously acquired skills, spasticity/dystonia, cerebral atrophy, and white matter changes. There is a high degree of non-penetrance, as 9/12 reported patients have inherited the PTPN1 variants from their asymptomatic parents. Hence, this gene is recommended for Green with expert review to determine if the non-penetrance is in scope of testing.
Childhood onset dystonia, chorea or related movement disorder v7.20 PTPN1 Ida Ertmanska Gene: ptpn1 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v7.19 PTPN1 Ida Ertmanska gene: PTPN1 was added
gene: PTPN1 was added to Childhood onset dystonia, chorea or related movement disorder. Sources: Literature
Q1_26_promote_green tags were added to gene: PTPN1.
Mode of inheritance for gene: PTPN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTPN1 were set to 10066179; 39986310
Phenotypes for gene: PTPN1 were set to Encephalopathy, HP:0001298; dystonia, early-onset, and/or spastic paraplegia, MONDO:0859215
Review for gene: PTPN1 was set to GREEN
Added comment: PMID: 39986310 Zhu et al., 2025
Reported heterozygous PTPN1 variants in 12 patients from 11 families. 2/10 were canonical splice variants, 2 were missense variants, and 6 were STOP-gain. 3 cases were de novo, 9 individuals inherited the variant from an asymptomatic parent. Sequencing method: WES + Sanger.

Phenotype: 12/12 individuals experienced subacute loss of skills (age range 15 months to 8 years) after initial normal development in 11 of 12 (one patient had mild motor delay); weakness (12/12), spasticity (initially manifesting as a hemiparesis in seven patients and then becoming bilateral) +/- dystonia, bulbar involvement (dysphagia and/or dysphasia) in 11/12 patients; absence of seizures. In 4/12 patients, fever and raised liver enzymes were noted around the time of presentation.

Brain MRI findings: Cerebral atrophy (9/12 patients), non-specific white matter changes (8/12), intracranial calcification (2/12). In 8 cases, the brain abnormalities resolved.Some patients demonstrated stabilisation / recovery of neurological function in the absence of treatment, while in others the disease appeared to respond to immune suppression.

Functional evidence: PMID: 10066179 Elchebly et al., 1999 - Ptpn1 knock-out (KO) mice are both viable and healthy, demonstrating enhanced insulin sensitivity and resistance to metabolic syndrome.

PTPN1 is associated with {Insulin resistance, susceptibility to}, MIM:1258539 in OMIM. It is not associated with disease in ClinGen or Gene2Phenotype (resources accessed 24 Mar 2026).
Probability of loss-of-function intolerance (pLI) score = 1.00 (predicted to be highly intolerant to LoF).
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v7.24 PTPN1 Ida Ertmanska Tag Q1_26_promote_green tag was added to gene: PTPN1.
White matter disorders and cerebral calcification - narrow panel v7.24 PTPN1 Ida Ertmanska edited their review of gene: PTPN1: Added comment: Comment on list classification: There are 11 unrelated individuals reported with heterozygous PTPN1 variants, presenting in childhood with loss of previously acquired skills, spasticity/dystonia, cerebral atrophy, and white matter changes. There is a high degree of non-penetrance, as 9/12 reported patients have inherited the PTPN1 variants from their asymptomatic parents. Hence, this gene is recommended for Green with expert review to determine if the non-penetrance is in scope of testing.; Changed rating: GREEN
Intellectual disability v9.351 PTPN1 Ida Ertmanska changed review comment from: Comment on list classification: There are 11 unrelated individuals reported with heterozygous PTPN1 variants, presenting with loss of previously acquired skills, spasticity/dystonia, cerebral atrophy, and white matter changes. There is a high degree of non-penetrance, as 9/12 reported patients have inherited the PTPN1 variants from their asymptomatic parents. Hence, this gene is recommended for Green with expert review to determine if the non-penetrance is in scope of testing.; to: Comment on list classification: There are 11 unrelated individuals reported with heterozygous PTPN1 variants, presenting in childhood with loss of previously acquired skills, spasticity/dystonia, cerebral atrophy, and white matter changes. There is a high degree of non-penetrance, as 9/12 reported patients have inherited the PTPN1 variants from their asymptomatic parents. Hence, this gene is recommended for Green with expert review to determine if the non-penetrance is in scope of testing.
Intellectual disability v9.351 PTPN1 Ida Ertmanska commented on gene: PTPN1: Comment on list classification: There are 11 unrelated individuals reported with heterozygous PTPN1 variants, presenting with loss of previously acquired skills, spasticity/dystonia, cerebral atrophy, and white matter changes. There is a high degree of non-penetrance, as 9/12 reported patients have inherited the PTPN1 variants from their asymptomatic parents. Hence, this gene is recommended for Green with expert review to determine if the non-penetrance is in scope of testing.
Intellectual disability v9.351 PTPN1 Ida Ertmanska Tag Q1_26_promote_green tag was added to gene: PTPN1.
Intellectual disability v9.351 PTPN1 Ida Ertmanska edited their review of gene: PTPN1: Changed rating: GREEN
Intellectual disability v9.351 PTPN1 Ida Ertmanska Phenotypes for gene: PTPN1 were changed from Encephalopathy, HP:0001298 to Encephalopathy, HP:0001298; dystonia, early-onset, and/or spastic paraplegia, MONDO:0859215
Intellectual disability v9.350 PTPN1 Ida Ertmanska edited their review of gene: PTPN1: Changed phenotypes to: Encephalopathy, HP:0001298, dystonia, early-onset, and/or spastic paraplegia, MONDO:0859215
White matter disorders and cerebral calcification - narrow panel v7.24 PTPN1 Ida Ertmanska edited their review of gene: PTPN1: Changed phenotypes to: Encephalopathy, HP:0001298, dystonia, early-onset, and/or spastic paraplegia, MONDO:0859215
White matter disorders and cerebral calcification - narrow panel v7.24 PTPN1 Ida Ertmanska Phenotypes for gene: PTPN1 were changed from Encephalopathy, HP:0001298 to Encephalopathy, HP:0001298; dystonia, early-onset, and/or spastic paraplegia, MONDO:0859215
Intellectual disability v9.350 PTPN1 Ida Ertmanska edited their review of gene: PTPN1: Changed publications to: 10066179, 39986310; Changed phenotypes to: Encephalopathy, HP:0001298
Intellectual disability v9.350 PTPN1 Ida Ertmanska Phenotypes for gene: PTPN1 were changed from to Encephalopathy, HP:0001298
White matter disorders and cerebral calcification - narrow panel v7.23 PTPN1 Ida Ertmanska Phenotypes for gene: PTPN1 were changed from to Encephalopathy, HP:0001298
White matter disorders and cerebral calcification - narrow panel v7.22 PTPN1 Ida Ertmanska edited their review of gene: PTPN1: Changed publications to: 10066179, 39986310; Changed phenotypes to: Encephalopathy, HP:0001298
White matter disorders and cerebral calcification - narrow panel v7.22 PTPN1 Ida Ertmanska Publications for gene: PTPN1 were set to 39986310
White matter disorders and cerebral calcification - narrow panel v7.21 PTPN1 Ida Ertmanska Classified gene: PTPN1 as Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v7.21 PTPN1 Ida Ertmanska Gene: ptpn1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v9.349 PTPN1 Ida Ertmanska Publications for gene: PTPN1 were set to 39986310
Intellectual disability v9.348 PTPN1 Ida Ertmanska Classified gene: PTPN1 as Amber List (moderate evidence)
Intellectual disability v9.348 PTPN1 Ida Ertmanska Gene: ptpn1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v9.347 PTPN1 Ida Ertmanska changed review comment from: PMID: 39986310 Zhu et al., 2025
Reported heterozygous PTPN1 variants in 12 patients from 11 families. 2/10 were canonical splice variants, 2 were missense variants, and 6 were STOP-gain. 3 cases were de novo, 9 individuals inherited the variant from an asymptomatic parent. Sequencing method: WES + Sanger.

Phenotype: 12/12 individuals experienced subacute loss of skills (age range 15 months to 8 years) after initial normal development in 11 of 12 (one patient had mild motor delay); weakness (12/12), spasticity (initially manifesting as a hemiparesis in seven patients and then becoming bilateral) +/- dystonia, bulbar involvement (dysphagia and/or dysphasia) in 11/12 patients; absence of seizures. In 4/12 patients, fever and raised liver enzymes were noted around the time of presentation.
Some patients demonstrated stabilisation / recovery of neurological function in the absence of treatment, while in others the disease appeared to respond to immune suppression.

PTPN1 is associated with {Insulin resistance, susceptibility to}, MIM:1258539 in OMIM. It is not associated with disease in ClinGen or Gene2Phenotype (resources accessed 24 Mar 2026).
Probability of loss-of-function intolerance (pLI) score = 1.00 (predicted to be highly intolerant to LoF).
Sources: Literature; to: PMID: 39986310 Zhu et al., 2025
Reported heterozygous PTPN1 variants in 12 patients from 11 families. 2/10 were canonical splice variants, 2 were missense variants, and 6 were STOP-gain. 3 cases were de novo, 9 individuals inherited the variant from an asymptomatic parent. Sequencing method: WES + Sanger.

Phenotype: 12/12 individuals experienced subacute loss of skills (age range 15 months to 8 years) after initial normal development in 11 of 12 (one patient had mild motor delay); weakness (12/12), spasticity (initially manifesting as a hemiparesis in seven patients and then becoming bilateral) +/- dystonia, bulbar involvement (dysphagia and/or dysphasia) in 11/12 patients; absence of seizures. In 4/12 patients, fever and raised liver enzymes were noted around the time of presentation.

Brain MRI findings: Cerebral atrophy (9/12 patients), non-specific white matter changes (8/12), intracranial calcification (2/12). In 8 cases, the brain abnormalities resolved.Some patients demonstrated stabilisation / recovery of neurological function in the absence of treatment, while in others the disease appeared to respond to immune suppression.

Functional evidence: PMID: 10066179 Elchebly et al., 1999 - Ptpn1 knock-out (KO) mice are both viable and healthy, demonstrating enhanced insulin sensitivity and resistance to metabolic syndrome.

PTPN1 is associated with {Insulin resistance, susceptibility to}, MIM:1258539 in OMIM. It is not associated with disease in ClinGen or Gene2Phenotype (resources accessed 24 Mar 2026).
Probability of loss-of-function intolerance (pLI) score = 1.00 (predicted to be highly intolerant to LoF).
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v7.20 PTPN1 Ida Ertmanska gene: PTPN1 was added
gene: PTPN1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
Mode of inheritance for gene: PTPN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTPN1 were set to 39986310
Review for gene: PTPN1 was set to AMBER
Added comment: PMID: 39986310 Zhu et al., 2025
Reported heterozygous PTPN1 variants in 12 patients from 11 families. 2/10 were canonical splice variants, 2 were missense variants, and 6 were STOP-gain. 3 cases were de novo, 9 individuals inherited the variant from an asymptomatic parent. Sequencing method: WES + Sanger.

Phenotype: 12/12 individuals experienced subacute loss of skills (age range 15 months to 8 years) after initial normal development in 11 of 12 (one patient had mild motor delay); weakness (12/12), spasticity (initially manifesting as a hemiparesis in seven patients and then becoming bilateral) +/- dystonia, bulbar involvement (dysphagia and/or dysphasia) in 11/12 patients; absence of seizures. In 4/12 patients, fever and raised liver enzymes were noted around the time of presentation.

Brain MRI findings: Cerebral atrophy (9/12 patients), non-specific white matter changes (8/12), intracranial calcification (2/12). In 8 cases, the brain abnormalities resolved.Some patients demonstrated stabilisation / recovery of neurological function in the absence of treatment, while in others the disease appeared to respond to immune suppression.

Functional evidence: PMID: 10066179 Elchebly et al., 1999 - Ptpn1 knock-out (KO) mice are both viable and healthy, demonstrating enhanced insulin sensitivity and resistance to metabolic syndrome.

PTPN1 is associated with {Insulin resistance, susceptibility to}, MIM:1258539 in OMIM. It is not associated with disease in ClinGen or Gene2Phenotype (resources accessed 24 Mar 2026).
Probability of loss-of-function intolerance (pLI) score = 1.00 (predicted to be highly intolerant to LoF).
Sources: Literature
Intellectual disability v9.347 PTPN1 Ida Ertmanska gene: PTPN1 was added
gene: PTPN1 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: PTPN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTPN1 were set to 39986310
Review for gene: PTPN1 was set to AMBER
Added comment: PMID: 39986310 Zhu et al., 2025
Reported heterozygous PTPN1 variants in 12 patients from 11 families. 2/10 were canonical splice variants, 2 were missense variants, and 6 were STOP-gain. 3 cases were de novo, 9 individuals inherited the variant from an asymptomatic parent. Sequencing method: WES + Sanger.

Phenotype: 12/12 individuals experienced subacute loss of skills (age range 15 months to 8 years) after initial normal development in 11 of 12 (one patient had mild motor delay); weakness (12/12), spasticity (initially manifesting as a hemiparesis in seven patients and then becoming bilateral) +/- dystonia, bulbar involvement (dysphagia and/or dysphasia) in 11/12 patients; absence of seizures. In 4/12 patients, fever and raised liver enzymes were noted around the time of presentation.
Some patients demonstrated stabilisation / recovery of neurological function in the absence of treatment, while in others the disease appeared to respond to immune suppression.

PTPN1 is associated with {Insulin resistance, susceptibility to}, MIM:1258539 in OMIM. It is not associated with disease in ClinGen or Gene2Phenotype (resources accessed 24 Mar 2026).
Probability of loss-of-function intolerance (pLI) score = 1.00 (predicted to be highly intolerant to LoF).
Sources: Literature
Severe microcephaly v8.36 LMNB2 Eleanor Williams changed review comment from: The mode of inheritance of this gene has been updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been kept as MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Severe microcephaly v8.36 LMNB2 Eleanor Williams changed review comment from: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Mitochondrial disorders v9.47 IDH1 Ida Ertmanska edited their review of gene: IDH1: Changed rating: AMBER
Mitochondrial disorders v9.47 IDH1 Ida Ertmanska Classified gene: IDH1 as Amber List (moderate evidence)
Mitochondrial disorders v9.47 IDH1 Ida Ertmanska Added comment: Comment on list classification: The rating of this gene has been updated to Amber following NHS Genomic Medicine Service approval. As all variants reported in this gene are somatic mosaic, they would not be reliably detected by a WGS test. Mosaic skin disorders - deep sequencing panel is more appropriate for IDH1 testing.
Mitochondrial disorders v9.47 IDH1 Ida Ertmanska Gene: idh1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v8.105 IDH1 Ida Ertmanska Classified gene: IDH1 as Amber List (moderate evidence)
Likely inborn error of metabolism v8.105 IDH1 Ida Ertmanska Added comment: Comment on list classification: The rating of this gene has been updated to Amber following NHS Genomic Medicine Service approval. As all variants reported in this gene are somatic mosaic, they would not be reliably detected by a WGS test. Mosaic skin disorders - deep sequencing panel is more appropriate for IDH1 testing.
Likely inborn error of metabolism v8.105 IDH1 Ida Ertmanska Gene: idh1 has been classified as Amber List (Moderate Evidence).
Skeletal dysplasia v8.39 IDH1 Ida Ertmanska Classified gene: IDH1 as Amber List (moderate evidence)
Skeletal dysplasia v8.39 IDH1 Ida Ertmanska Added comment: Comment on list classification: The rating of this gene has been updated to Amber following NHS Genomic Medicine Service approval. As all variants reported in this gene are somatic mosaic, they would not be reliably detected by a WGS test. Mosaic skin disorders - deep sequencing panel is more appropriate for IDH1 testing.
Skeletal dysplasia v8.39 IDH1 Ida Ertmanska Gene: idh1 has been classified as Amber List (Moderate Evidence).
Paediatric or syndromic cardiomyopathy v7.99 POPDC2 Ludmila Volozonoka reviewed gene: POPDC2: Rating: ; Mode of pathogenicity: None; Publications: 41456958, 40409267; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v9.346 MYCBP2 Ludmila Volozonoka gene: MYCBP2 was added
gene: MYCBP2 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: MYCBP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYCBP2 were set to 41200582; 36200388; 41543631
Review for gene: MYCBP2 was set to GREEN
Added comment: PMID: 36200388 reports eight de novo MYCBP2 variants (two loss-of-function and six missense) in patients presenting with dysmorphism, global developmental delay, varying degrees of intellectual disability, language delay, and ASD. Less common features include corpus callosum dysgenesis and epilepsy.

PMID: 41200582 describes a loss-of-function MYCBP2 variant identified in a mother and her two sons, all exhibiting similar clinical features as in PMID: 36200388.

PMID: 41543631 demonstrates another loss-of-function variant in a proband with NDD, inherited from a mother with mild features (notably subtle executive dysfunction).
The gene is highly constrained of LOF variants in a general population (pLI = 1).
Sources: Literature
Fetal anomalies v6.181 ITCH Ludmila Volozonoka reviewed gene: ITCH: Rating: GREEN; Mode of pathogenicity: None; Publications: 36338154; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Monogenic diabetes v3.14 ZNF808 Ida Ertmanska Tag Q1_26_promote_green tag was added to gene: ZNF808.
Tag Q1_26_NHS_review tag was added to gene: ZNF808.
Monogenic diabetes v3.14 ZNF808 Ida Ertmanska changed review comment from: PMID: 41500078 Russ-Silsby et al 2026
17 previously unreported individuals with biallelic loss-of-function ZNF808 variants.19 individuals had permanent neonatal diabetes; 12 had other diabetes phenotypes: 5 with infancy-onset diabetes, 4 with transient diabetes and 3 with diabetes diagnosed aged 10, 14 and 23 years.
Variable severity associated with the variants e.g.,:
p.(Thr630Serfs*24) was detected in a homozyogus state in Patient 14 (diabetes diagnosed at 23 yrs), as well as Patient 1 (PNDM diagnosed at 13 weeks), and in patient 11 (transient diabetes diagnosed at 1 day old).
p.(Tyr662*) detected in homozygous state in Patient 15 (diabetes diagnosed at 10yo) and heterozygous, in trans with a deletion, in Patient 13 (diabetes diagnosed at 14 years.; to: PMID: 41500078 Russ-Silsby et al 2026
17 previously unreported individuals with biallelic loss-of-function ZNF808 variants.19 individuals had permanent neonatal diabetes; 12 had other diabetes phenotypes: 5 with infancy-onset diabetes, 4 with transient diabetes and 3 with diabetes diagnosed aged 10, 14 and 23 years.
Variable severity associated with the variants e.g.,:
p.(Thr630Serfs*24) was detected in a homozyogus state in Patient 14 (diabetes diagnosed at 23 yrs), as well as Patient 1 (PNDM diagnosed at 13 weeks), and in patient 11 (transient diabetes diagnosed at 1 day old).
p.(Tyr662*) detected in homozygous state in Patient 15 (diabetes diagnosed at 10yo) and heterozygous, in trans with a deletion, in Patient 13 (diabetes diagnosed at 14 years).
Intellectual disability v9.346 SOD1 Ida Ertmanska Tag treatable tag was added to gene: SOD1.
Intellectual disability v9.346 SOD1 Ida Ertmanska commented on gene: SOD1
Childhood onset hereditary spastic paraplegia v8.42 SOD1 Ida Ertmanska Tag treatable tag was added to gene: SOD1.
Childhood onset hereditary spastic paraplegia v8.42 SOD1 Ida Ertmanska commented on gene: SOD1
Adult onset neurodegenerative disorder v8.21 SOD1 Ida Ertmanska Phenotypes for gene: SOD1 were changed from Amyotrophic lateral sclerosis 1, OMIM:105400 to Amyotrophic lateral sclerosis 1, OMIM:105400; Spastic tetraplegia and axial hypotonia, progressive, OMIM:618598
Adult onset neurodegenerative disorder v8.20 SOD1 Ida Ertmanska commented on gene: SOD1
Adult onset neurodegenerative disorder v8.20 SOD1 Ida Ertmanska Tag treatable tag was added to gene: SOD1.
Hereditary neuropathy or pain disorder v7.45 SOD1 Ida Ertmanska commented on gene: SOD1: Tofersen is a genetic therapy developed for a rare inherited form of motor neurone disease (MND) caused by mutations in the SOD1 gene. The MHRA approved Tofersen in July 2025 for adults with SOD1‑related MND; however, it has not been approved by NICE for routine NHS use, and the NICE appraisal process is ongoing. Hence, 'treatable' tag has been added.
Paediatric disorders - additional genes v7.37 ACVR2B Ida Ertmanska Deleted their comment
Paediatric disorders - additional genes v7.37 ACVR2B Ida Ertmanska commented on gene: ACVR2B: Tofersen is a genetic therapy developed for a rare inherited form of motor neurone disease (MND) caused by mutations in the SOD1 gene. The MHRA approved Tofersen in July 2025 for adults with SOD1‑related MND; however, it has not been approved by NICE for routine NHS use, and the NICE appraisal process is ongoing. Hence, 'treatable' tag has been added.
Hereditary neuropathy or pain disorder v7.45 SOD1 Ida Ertmanska Tag treatable tag was added to gene: SOD1.
Paediatric disorders - additional genes v7.37 ACVR2B Ida Ertmanska changed review comment from: PMID: 9916847 Kosaki et al., 1999
Report of 3 patients who are heterozygous for variants p.(R40H), p.V494I (1999 paper).
ACVR2B:c.1480G>A p.Val494Ile is rare in gnomAD v4 (14 alleles reported, no homozygotes, MAF = 0.00003378).
ACVR2B:c.119G>A, p.Arg40His mutation has 4 homozygotes in the population (gnomAD) and >350 heterozygotes - too common for a rare dominant disorder.

PMID: 21864452 Ma et al., 2011
Two unrelated patients with heterotaxy and a recurring missense (p.R40H). Unaffected mothers are carriers = variant did not segregate with disease.

PMID: 30622330 Li et al., 2019
Pedigree with a heterozygous missense variant in ACVR2B and heterotaxy. Family 1: c.1147C>T, p.Arg383Cys missense variant in ACVR2B was inherited from an affected parent, clear segregation of the variant with five affected individuals from three generations. The variant is not present in gnomAD v4, and it is classified as LP in ClinVar.

PMID: 35547246 Antony et al., 2022
Family SI-47 - proband with Situs inversus totalis had a heterozygous ACVR2B variant c.925C>T, p.Arg309Cys and a homozygous c.350A>G, p.Asp117Gly variant in CCDC39. CCDC39 is associated with recessive Ciliary dyskinesia, primary, 14, OMIM:613807. Effect of each variant is unclear. The p.Arg309Cys variant is rare in gnomAD v4, with 30 alleles reported and no homozygotes (MAF = 0.00005490); VUS in ClinVar.

Functional evidence:
PMID: 9242489 Oh & Li 1997 - knockout acvr2b -/- mice die after birth with complicated cardiac defects including randomized heart position, malposition of the great arteries, and ventricular and atrial septal defects; the heart anomalies are associated with right pulmonary isomerism and splenic abnormalities.
PMID: 21864452 Ma et al., 2011 - Activin receptor IIB (Acvr2b) is expressed asymmetrically along left-right axis in mouse and chick

The gene is associated with AD Heterotaxy, visceral, 4, autosomal, MIM:613751 in OMIM. ACVR2B has not been curated in ClinGen and it is limited in Gene2Phenotype.; to: PMID: 9916847 Kosaki et al., 1999
Report of 3 patients who are heterozygous for variants p.(R40H), p.V494I (1999 paper).
ACVR2B:c.1480G>A p.Val494Ile is rare in gnomAD v4 (14 alleles reported, no homozygotes, MAF = 0.00003378).
ACVR2B:c.119G>A, p.Arg40His mutation has 4 homozygotes in the population (gnomAD) and >350 heterozygotes - too common for a rare dominant disorder.

PMID: 21864452 Ma et al., 2011
Two unrelated patients with heterotaxy and a recurring missense (p.R40H). Unaffected mothers are carriers = variant did not segregate with disease.

PMID: 30622330 Li et al., 2019
Pedigree with a heterozygous missense variant in ACVR2B and heterotaxy. Family 1: c.1147C>T, p.Arg383Cys missense variant in ACVR2B was inherited from an affected parent, clear segregation of the variant with five affected individuals from three generations. The variant is not present in gnomAD v4, and it is classified as LP in ClinVar.

PMID: 35547246 Antony et al., 2022
Family SI-47 - proband with Situs inversus totalis had a heterozygous ACVR2B variant c.925C>T, p.Arg309Cys and a homozygous c.350A>G, p.Asp117Gly variant in CCDC39. CCDC39 is associated with recessive Ciliary dyskinesia, primary, 14, OMIM:613807. Effect of each variant is unclear. The p.Arg309Cys variant is rare in gnomAD v4, with 30 alleles reported and no homozygotes (MAF = 0.00005490); VUS in ClinVar.

Functional evidence:
PMID: 9242489 Oh & Li 1997 - knockout acvr2b -/- mice die after birth with complicated cardiac defects including randomized heart position, malposition of the great arteries, and ventricular and atrial septal defects; the heart anomalies are associated with right pulmonary isomerism and splenic abnormalities.
PMID: 17849440 Goto et al., 2007 - The acvr2b+/− mice were revealed to be normal and viable; left–right patterning defects seen in some of the (acvr2b+/−smad2+/−) mice - digenic inheritance?
PMID: 21864452 Ma et al., 2011 - Activin receptor IIB (Acvr2b) is expressed asymmetrically along left-right axis in mouse and chick

The gene is associated with AD Heterotaxy, visceral, 4, autosomal, MIM:613751 in OMIM. ACVR2B has not been curated in ClinGen and it is limited in Gene2Phenotype.
Paediatric disorders - additional genes v7.37 ACVR2B Ida Ertmanska changed review comment from: PMID: 9916847 Kosaki et al., 1999
Report of 3 patients who are heterozygous for variants p.(R40H), p.V494I (1999 paper).
ACVR2B:c.1480G>A p.Val494Ile is rare in gnomAD v4 (14 alleles reported, no homozygotes, MAF = 0.00003378).
ACVR2B:c.119G>A, p.Arg40His mutation has 4 homozygotes in the population (gnomAD) and >350 heterozygotes - too common for a rare dominant disorder.

PMID: 21864452 Ma et al., 2012
Two unrelated patients with heterotaxy and a recurring missense (p.R40H). Unaffected mothers are carriers = variant did not segregate with disease.

PMID: 30622330 Li et al., 2019
Pedigree with a heterozygous missense variant in ACVR2B and heterotaxy. Family 1: c.1147C>T, p.Arg383Cys missense variant in ACVR2B was inherited from an affected parent, clear segregation of the variant with five affected individuals from three generations. The variant is not present in gnomAD v4, and it is classified as LP in ClinVar.

PMID: 35547246 Antony et al., 2022
Family SI-47 - proband with Situs inversus totalis had a heterozygous ACVR2B variant c.925C>T, p.Arg309Cys and a homozygous c.350A>G, p.Asp117Gly variant in CCDC39. CCDC39 is associated with recessive Ciliary dyskinesia, primary, 14, OMIM:613807. Effect of each variant is unclear. The p.Arg309Cys variant is rare in gnomAD v4, with 30 alleles reported and no homozygotes (MAF = 0.00005490); VUS in ClinVar.

The gene is associated with AD Heterotaxy, visceral, 4, autosomal, MIM:613751 in OMIM. ACVR2B has not been curated in ClinGen and it is limited in Gene2Phenotype.; to: PMID: 9916847 Kosaki et al., 1999
Report of 3 patients who are heterozygous for variants p.(R40H), p.V494I (1999 paper).
ACVR2B:c.1480G>A p.Val494Ile is rare in gnomAD v4 (14 alleles reported, no homozygotes, MAF = 0.00003378).
ACVR2B:c.119G>A, p.Arg40His mutation has 4 homozygotes in the population (gnomAD) and >350 heterozygotes - too common for a rare dominant disorder.

PMID: 21864452 Ma et al., 2011
Two unrelated patients with heterotaxy and a recurring missense (p.R40H). Unaffected mothers are carriers = variant did not segregate with disease.

PMID: 30622330 Li et al., 2019
Pedigree with a heterozygous missense variant in ACVR2B and heterotaxy. Family 1: c.1147C>T, p.Arg383Cys missense variant in ACVR2B was inherited from an affected parent, clear segregation of the variant with five affected individuals from three generations. The variant is not present in gnomAD v4, and it is classified as LP in ClinVar.

PMID: 35547246 Antony et al., 2022
Family SI-47 - proband with Situs inversus totalis had a heterozygous ACVR2B variant c.925C>T, p.Arg309Cys and a homozygous c.350A>G, p.Asp117Gly variant in CCDC39. CCDC39 is associated with recessive Ciliary dyskinesia, primary, 14, OMIM:613807. Effect of each variant is unclear. The p.Arg309Cys variant is rare in gnomAD v4, with 30 alleles reported and no homozygotes (MAF = 0.00005490); VUS in ClinVar.

Functional evidence:
PMID: 9242489 Oh & Li 1997 - knockout acvr2b -/- mice die after birth with complicated cardiac defects including randomized heart position, malposition of the great arteries, and ventricular and atrial septal defects; the heart anomalies are associated with right pulmonary isomerism and splenic abnormalities.
PMID: 21864452 Ma et al., 2011 - Activin receptor IIB (Acvr2b) is expressed asymmetrically along left-right axis in mouse and chick

The gene is associated with AD Heterotaxy, visceral, 4, autosomal, MIM:613751 in OMIM. ACVR2B has not been curated in ClinGen and it is limited in Gene2Phenotype.
Paediatric disorders - additional genes v7.37 ACVR2B Ida Ertmanska changed review comment from: PMID: 9916847 Kosaki et al., 1999
Report of 3 patients who are heterozygous for variants p.(R40H), p.V494I (1999 paper).

PMID: 21864452 Ma et al., 2012
Two unrelated patients with heterotaxy and a recurring missense (p.R40H). Unaffected mothers are carriers = variant did not segregate with disease. The p.Arg40His mutation has 4 homozygotes in the population (gnomAD) and >350 heterozygotes - too common for a rare disorder.

PMID: 30622330 Li et al., 2019
Pedigree with a heterozygous missense variant in ACVR2B and heterotaxy. Family 1: p.(R383C) missense variant in ACVR2B was inherited from an affected parent, clear segregation of the variant with five affected individuals from three generations. The variant is not present in gnomAD v4, and it is classified as LP in ClinVar.

PMID: 35547246 Antony et al., 2022
Family SI-47 - proband with Situs inversus totalis had a heterozygous ACVR2B variant c.925C>T, p.Arg309Cys and a homozygous c.350A>G, p.Asp117Gly variant in CCDC39. CCDC39 is associated with recessive Ciliary dyskinesia, primary, 14, OMIM:613807. Effect of each variant is unclear.; to: PMID: 9916847 Kosaki et al., 1999
Report of 3 patients who are heterozygous for variants p.(R40H), p.V494I (1999 paper).
ACVR2B:c.1480G>A p.Val494Ile is rare in gnomAD v4 (14 alleles reported, no homozygotes, MAF = 0.00003378).
ACVR2B:c.119G>A, p.Arg40His mutation has 4 homozygotes in the population (gnomAD) and >350 heterozygotes - too common for a rare dominant disorder.

PMID: 21864452 Ma et al., 2012
Two unrelated patients with heterotaxy and a recurring missense (p.R40H). Unaffected mothers are carriers = variant did not segregate with disease.

PMID: 30622330 Li et al., 2019
Pedigree with a heterozygous missense variant in ACVR2B and heterotaxy. Family 1: c.1147C>T, p.Arg383Cys missense variant in ACVR2B was inherited from an affected parent, clear segregation of the variant with five affected individuals from three generations. The variant is not present in gnomAD v4, and it is classified as LP in ClinVar.

PMID: 35547246 Antony et al., 2022
Family SI-47 - proband with Situs inversus totalis had a heterozygous ACVR2B variant c.925C>T, p.Arg309Cys and a homozygous c.350A>G, p.Asp117Gly variant in CCDC39. CCDC39 is associated with recessive Ciliary dyskinesia, primary, 14, OMIM:613807. Effect of each variant is unclear. The p.Arg309Cys variant is rare in gnomAD v4, with 30 alleles reported and no homozygotes (MAF = 0.00005490); VUS in ClinVar.

The gene is associated with AD Heterotaxy, visceral, 4, autosomal, MIM:613751 in OMIM. ACVR2B has not been curated in ClinGen and it is limited in Gene2Phenotype.
Likely inborn error of metabolism v8.104 SLC52A3 Achchuthan Shanmugasundram commented on gene: SLC52A3: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Likely inborn error of metabolism v8.104 SLC52A3 Achchuthan Shanmugasundram Mode of inheritance for gene: SLC52A3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Likely inborn error of metabolism v8.103 SLC52A3 Achchuthan Shanmugasundram Tag Q1_26_MOI was removed from gene: SLC52A3.
Congenital myaesthenic syndrome v5.8 UNC13A Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotype updated 23 Mar 2026.
Congenital myaesthenic syndrome v5.8 UNC13A Ida Ertmanska Phenotypes for gene: UNC13A were changed from congenital myasthenic syndrome, MONDO:0018940 to congenital myasthenic syndrome, MONDO:0018940; Neurodevelopmental disorder with hypotonia, epilepsy, and absent speech, OMIM:621455
Early onset or syndromic epilepsy v8.168 UNC13A Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotypes updated 23 Mar 2026.
Early onset or syndromic epilepsy v8.168 UNC13A Ida Ertmanska Phenotypes for gene: UNC13A were changed from developmental and epileptic encephalopathy, MONDO:0100620 to Neurodevelopmental disorder with speech delay, movement abnormalities, and seizures, OMIM:621456; Neurodevelopmental disorder with hypotonia, epilepsy, and absent speech, OMIM:621455; ?Intellectual development disorder with seizures and dysmorphic facies , OMIM:621457
Intellectual disability v9.346 UNC13A Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotype updated 23 Mar 2026.
Intellectual disability v9.346 UNC13A Ida Ertmanska Phenotypes for gene: UNC13A were changed from developmental and epileptic encephalopathy, MONDO:0100620 to Neurodevelopmental disorder with speech delay, movement abnormalities, and seizures, OMIM:621456; Neurodevelopmental disorder with hypotonia, epilepsy, and absent speech, OMIM:621455; ?Intellectual development disorder with seizures and dysmorphic facies , OMIM:621457
Paediatric or syndromic cardiomyopathy v7.99 POPDC2 Dmitrijs Rots gene: POPDC2 was added
gene: POPDC2 was added to Paediatric or syndromic cardiomyopathy. Sources: Literature
Mode of inheritance for gene: POPDC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POPDC2 were set to PMID: 40409267
Phenotypes for gene: POPDC2 were set to cardiac conduction defects and hypertrophic cardiomyopathy
Penetrance for gene: POPDC2 were set to unknown
Review for gene: POPDC2 was set to GREEN
Added comment: PMID: 40409267 reports 4 families with recessive inheritance with presenting with cardiac conduction defects and hypertrophic cardiomyopathy with some functional evidence. enough for green rating.
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v7.19 ALPK1 Dmitrijs Rots gene: ALPK1 was added
gene: ALPK1 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
Mode of inheritance for gene: ALPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALPK1 were set to PMID: 35868845
Phenotypes for gene: ALPK1 were set to ROSAH
Penetrance for gene: ALPK1 were set to Complete
Mode of pathogenicity for gene: ALPK1 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: ALPK1 was set to GREEN
Added comment: Associated with ROSAH syndrome, but the phenotype is variable among the individuals. The authors of PMID: 35868845 report:" However, seven of the patients had premature mineralisation/calcification of the globus pallidi, red nuclei and substantia nigra, worsening with age, eventually involving the rest of the basal ganglia (figure 2E). White matter abnormalities have also been reported and patient F10.1 initially received a diagnosis of multiple sclerosis after she presented with loss of colour vision and was reported to have multiple lesions on MRI.".

The gene is currently not in any "brain" panels, while showing obvious brain abnormalities.
Sources: Literature
Pigmentary skin disorders v4.13 XRCC2 Veronica Kinsler reviewed gene: XRCC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 41526458, 22232082, 27208205, 30042186; Phenotypes: Fanconi anaemia; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pigmentary skin disorders v4.13 SNAI2 Veronica Kinsler reviewed gene: SNAI2: Rating: GREEN; Mode of pathogenicity: None; Publications: 12444107, 12955764, 30936914; Phenotypes: Waardenburg syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Pigmentary skin disorders v4.13 MLPH Veronica Kinsler reviewed gene: MLPH: Rating: GREEN; Mode of pathogenicity: None; Publications: 12897212, 21883982, 22711375, 26337734; Phenotypes: Griscelli syndrome; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v8.103 SLC52A3 Achchuthan Shanmugasundram changed review comment from: There is strong evidence available for the association of biallelic variants in SLC52A3 with human disease. Biallelic variants are associated with relevant phenotypes in OMIM (MIMs #211530 & #211500, last accessed 20 March 2026) and Gene2Phenotype (with definitive ratings on DD and Ear panels). Autosomal recessive variants are associated with Brown-Vialetto-van Laere syndrome 1 phenotype (MONDO:0024537) with 'definitive' rating on ClinGen by the Hearing Loss GCEP (https://search.clinicalgenome.org/CCID:006194).

There is also evidence available for the association of monoallelic SLC52A3 variants with human disease, despite not being associated with phenotypes in OMIM, G2P, ClinGen or PanelApp Australia.

PMID:22718020 (2012) reported three patients with Brown-Vialetto-Van Laere syndrome. Variant in only one allele was identified in SLC52A3 by Sanger sequencing in two of these three patents.

PMID:29053833 (2017) reported five patients with monoallelic variants identified by PCR and Sanger sequencing. They showed phenotypes indistinguishable from biallelic cases in severity, age of onset, and clinical features. The authors used array CGH to exclude large deletions/duplications on the second allele.

PMID:34384672 (2021) reported three patients with adult-onset Brown-Vialetto-van Laere syndrome and with SLC52A3 variants, of which one patient was identified with a heterozygous variant.
​
PMID:38469093 (2024) reported a 16-year-old female with a phenotype consistent with riboflavin transporter deficiency. She was identified with a novel heterozygous variant, identified by WGS. Her asymptomatic brother was also identified with the same heterozygous variant, directly demonstrating reduced penetrance for this monoallelic state. Her condition however improved in response to riboflavin supplementation.

PMID:40539137 (2025) reported a 68-year-old female patient with atypical late-onset Brown-Vialetto-Van Laere syndrome carrying a variant (p.Val413Ala) previously seen only in compound heterozygous patients in heterozygous state.; to: There is strong evidence available for the association of biallelic variants in SLC52A3 with human disease. Biallelic variants are associated with relevant phenotypes in OMIM (MIMs #211530 & #211500, last accessed 20 March 2026) and Gene2Phenotype (with definitive ratings on DD and Ear panels). Autosomal recessive variants are associated with Brown-Vialetto-van Laere syndrome 1 phenotype (MONDO:0024537) with 'definitive' rating on ClinGen by the Hearing Loss GCEP (https://search.clinicalgenome.org/CCID:006194).

There is also evidence available for the association of monoallelic SLC52A3 variants with human disease, despite not being associated with phenotypes in OMIM, G2P, ClinGen or PanelApp Australia.

PMID:22718020 (2012) reported three patients with Brown-Vialetto-Van Laere syndrome. Variant in only one allele was identified in SLC52A3 by Sanger sequencing in two of these three patents.

PMID:29053833 (2017) reported five patients with monoallelic variants identified by PCR and Sanger sequencing. They showed phenotypes indistinguishable from biallelic cases in severity, age of onset, and clinical features. The authors used array CGH to exclude large deletions/duplications on the second allele.

PMID:34384672 (2021) reported three patients with adult-onset Brown-Vialetto-van Laere syndrome and with SLC52A3 variants, of which one patient was identified with a heterozygous variant.
​
PMID:38469093 (2024) reported a 16-year-old female with a phenotype consistent with riboflavin transporter deficiency. She was identified with a novel heterozygous variant, identified by WGS. Her asymptomatic brother was also identified with the same heterozygous variant, directly demonstrating reduced penetrance for this monoallelic state. Her condition however improved in response to riboflavin supplementation.

PMID:40539137 (2025) reported a 68-year-old female patient with atypical late-onset Brown-Vialetto-Van Laere syndrome carrying a variant (p.Val413Ala) previously seen only in compound heterozygous patients in heterozygous state.
Likely inborn error of metabolism v8.103 SLC52A3 Achchuthan Shanmugasundram changed review comment from: There is strong evidence available for the association of biallelic variants in SLC52A3 with human disease. Biallelic variants are associated with relevant phenotypes in OMIM (MIMs #211530 & #211500, last accessed 20 March 2026) and Gene2Phenotype (with definitive ratings on DD and Ear panels). Autosomal recessive variants are associated with Brown-Vialetto-van Laere syndrome 1 phenotype (MONDO:0024537) with 'definitive' rating on ClinGen by the Hearing Loss GCEP (https://search.clinicalgenome.org/CCID:006194).

There is also evidence available for the association of monoallelic SLC52A3 variants with human disease, despite not being associated with phenotypes in OMIM, G2P, ClinGen or PanelApp Australia.

PMID:22718020 (2012) reported three patients with Brown-Vialetto-Van Laere syndrome. Only one variant was identified in SLC52A3 by Sanger sequencing in two of these three patents.

PMID:29053833 (2017) reported five patients with monoallelic variants identified by PCR and Sanger sequencing. They showed phenotypes indistinguishable from biallelic cases in severity, age of onset, and clinical features. The authors used array CGH to exclude large deletions/duplications on the second allele.

PMID:34384672 (2021) reported three patients with adult-onset Brown-Vialetto-van Laere syndrome and with SLC52A3 variants, of which one patient was identified with a heterozygous variant.
​
PMID:38469093 (2024) reported a 16-year-old female with a phenotype consistent with riboflavin transporter deficiency. She was identified with a novel heterozygous variant, identified by WGS. Her asymptomatic brother was also identified with the same heterozygous variant, directly demonstrating reduced penetrance for this monoallelic state. Her condition however improved in response to riboflavin supplementation.

PMID:40539137 (2025) reported a 68-year-old female patient with atypical late-onset Brown-Vialetto-Van Laere syndrome carrying a variant (p.Val413Ala) previously seen only in compound heterozygous patients in heterozygous state.; to: There is strong evidence available for the association of biallelic variants in SLC52A3 with human disease. Biallelic variants are associated with relevant phenotypes in OMIM (MIMs #211530 & #211500, last accessed 20 March 2026) and Gene2Phenotype (with definitive ratings on DD and Ear panels). Autosomal recessive variants are associated with Brown-Vialetto-van Laere syndrome 1 phenotype (MONDO:0024537) with 'definitive' rating on ClinGen by the Hearing Loss GCEP (https://search.clinicalgenome.org/CCID:006194).

There is also evidence available for the association of monoallelic SLC52A3 variants with human disease, despite not being associated with phenotypes in OMIM, G2P, ClinGen or PanelApp Australia.

PMID:22718020 (2012) reported three patients with Brown-Vialetto-Van Laere syndrome. Variant in only one allele was identified in SLC52A3 by Sanger sequencing in two of these three patents.

PMID:29053833 (2017) reported five patients with monoallelic variants identified by PCR and Sanger sequencing. They showed phenotypes indistinguishable from biallelic cases in severity, age of onset, and clinical features. The authors used array CGH to exclude large deletions/duplications on the second allele.

PMID:34384672 (2021) reported three patients with adult-onset Brown-Vialetto-van Laere syndrome and with SLC52A3 variants, of which one patient was identified with a heterozygous variant.
​
PMID:38469093 (2024) reported a 16-year-old female with a phenotype consistent with riboflavin transporter deficiency. She was identified with a novel heterozygous variant, identified by WGS. Her asymptomatic brother was also identified with the same heterozygous variant, directly demonstrating reduced penetrance for this monoallelic state. Her condition however improved in response to riboflavin supplementation.

PMID:40539137 (2025) reported a 68-year-old female patient with atypical late-onset Brown-Vialetto-Van Laere syndrome carrying a variant (p.Val413Ala) previously seen only in compound heterozygous patients in heterozygous state.
Likely inborn error of metabolism v8.103 SLC52A3 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There is evidence available for the association of both monoallelic and biallelic variants in this gene to riboflavin transporter deficiency. The MOI of this gene has already been set to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' on Mitochondrial disorders panel (https://panelapp.genomicsengland.co.uk/panels/112/gene/SLC52A3/). Hence, the MOI should be updated to BOTH on this panel.
Likely inborn error of metabolism v8.103 SLC52A3 Achchuthan Shanmugasundram Mode of inheritance for gene: SLC52A3 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v8.102 SLC52A3 Achchuthan Shanmugasundram Tag Q1_26_MOI tag was added to gene: SLC52A3.
Likely inborn error of metabolism v8.102 SLC52A3 Achchuthan Shanmugasundram Phenotypes for gene: SLC52A3 were changed from Brown-Vialetto-Van Laere syndrome 1 211530; Fazio-Londe disease 211500 to Brown-Vialetto-Van Laere syndrome 1, OMIM:211530; Brown-Vialetto-van Laere syndrome 1, MONDO:0024537; ?Fazio-Londe disease, OMIM:211500; riboflavin transporter deficiency, MONDO:0008891
Likely inborn error of metabolism v8.101 SLC52A3 Achchuthan Shanmugasundram Publications for gene: SLC52A3 were set to
Likely inborn error of metabolism v8.100 SLC52A3 Achchuthan Shanmugasundram changed review comment from: There is strong evidence available for the association of biallelic variants in SLC52A3 with human disease. Biallelic variants are associated with relevant phenotypes in OMIM (MIMs #211530 & #211500, last accessed 20 March 2026) and Gene2Phenotype (with definitive ratings on DD and Ear panels). Autosomal recessive variants are associated with Brown-Vialetto-van Laere syndrome 1 phenotype (MONDO:0024537) with 'definitive' rating on ClinGen by the Hearing Loss GCEP (https://search.clinicalgenome.org/CCID:006194).

There is also evidence available for the association of monoallelic SLC52A3 variants with human disease, despite not being associated with phenotypes in OMIM, G2P, ClinGen or PanelApp Australia.

PMID:22718020 (2012) reported three patients with Brown-Vialetto-Van Laere syndrome. Only one variant was identified in SLC52A3 by Sanger sequencing in two of these three patents.

PMID:29053833 (2017) reported five patients with monoallelic variants identified by PCR and Sanger sequencing. They showed phenotypes indistinguishable from biallelic cases in severity, age of onset, and clinical features. The authors used array CGH to exclude large deletions/duplications on the second allele.

PMID:34384672 (2021) reported three patients with SLC52A3 variants, of which one patient was identified with a heterozygous variant.
​
PMID:38469093 (2024) reported a 16-year-old female with a phenotype consistent with riboflavin transporter deficiency. She was identified with a novel heterozygous variant, identified by WGS. Her asymptomatic brother was also identified with the same heterozygous variant, directly demonstrating reduced penetrance for this monoallelic state. Her condition however improved in response to riboflavin supplementation.

PMID:40539137 (2025) reported a 68-year-old female patient with atypical late-onset Brown-Vialetto-Van Laere syndrome carrying a variant (p.Val413Ala) previously seen only in compound heterozygous patients in heterozygous state.; to: There is strong evidence available for the association of biallelic variants in SLC52A3 with human disease. Biallelic variants are associated with relevant phenotypes in OMIM (MIMs #211530 & #211500, last accessed 20 March 2026) and Gene2Phenotype (with definitive ratings on DD and Ear panels). Autosomal recessive variants are associated with Brown-Vialetto-van Laere syndrome 1 phenotype (MONDO:0024537) with 'definitive' rating on ClinGen by the Hearing Loss GCEP (https://search.clinicalgenome.org/CCID:006194).

There is also evidence available for the association of monoallelic SLC52A3 variants with human disease, despite not being associated with phenotypes in OMIM, G2P, ClinGen or PanelApp Australia.

PMID:22718020 (2012) reported three patients with Brown-Vialetto-Van Laere syndrome. Only one variant was identified in SLC52A3 by Sanger sequencing in two of these three patents.

PMID:29053833 (2017) reported five patients with monoallelic variants identified by PCR and Sanger sequencing. They showed phenotypes indistinguishable from biallelic cases in severity, age of onset, and clinical features. The authors used array CGH to exclude large deletions/duplications on the second allele.

PMID:34384672 (2021) reported three patients with adult-onset Brown-Vialetto-van Laere syndrome and with SLC52A3 variants, of which one patient was identified with a heterozygous variant.
​
PMID:38469093 (2024) reported a 16-year-old female with a phenotype consistent with riboflavin transporter deficiency. She was identified with a novel heterozygous variant, identified by WGS. Her asymptomatic brother was also identified with the same heterozygous variant, directly demonstrating reduced penetrance for this monoallelic state. Her condition however improved in response to riboflavin supplementation.

PMID:40539137 (2025) reported a 68-year-old female patient with atypical late-onset Brown-Vialetto-Van Laere syndrome carrying a variant (p.Val413Ala) previously seen only in compound heterozygous patients in heterozygous state.
Likely inborn error of metabolism v8.100 SLC52A3 Achchuthan Shanmugasundram edited their review of gene: SLC52A3: Changed publications to: 22718020, 29053833, 34384672, 38469093, 40539137; Changed phenotypes to: Brown-Vialetto-Van Laere syndrome 1, OMIM:211530, Brown-Vialetto-van Laere syndrome 1, MONDO:0024537, ?Fazio-Londe disease, OMIM:211500, riboflavin transporter deficiency, MONDO:0008891
Likely inborn error of metabolism v8.100 SLC52A3 Achchuthan Shanmugasundram reviewed gene: SLC52A3: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Paediatric disorders - additional genes v7.37 ACVR2B Ida Ertmanska edited their review of gene: ACVR2B: Changed publications to: 9916847, 21864452, 30622330, 35547246
Paediatric disorders - additional genes v7.37 ACVR2B Ida Ertmanska changed review comment from: PMID: 9916847 Kosaki et al., 1999
Report of 3 patients who are heterozygous for variants p.(R40H), p.V494I (1999 paper).

PMID: 21864452 Ma et al., 2012
Two unrelated patients with heterotaxy and a recurring missense (p.R40H). Unaffected mothers are carriers = variant did not segregate with disease. The p.Arg40His mutation has 4 homozygotes in the population (gnomAD) and >350 heterozygotes - too common for a rare disorder.

PMID: 30622330 Li et al., 2019
Pedigree with a heterozygous missense variant in ACVR2B and heterotaxy. Family 1: p.(R383C) missense variant in ACVR2B was inherited from an affected parent, clear segregation of the variant with five affected individuals from three generations. The variant is not present in gnomAD v4, and it is classified as LP in ClinVar.; to: PMID: 9916847 Kosaki et al., 1999
Report of 3 patients who are heterozygous for variants p.(R40H), p.V494I (1999 paper).

PMID: 21864452 Ma et al., 2012
Two unrelated patients with heterotaxy and a recurring missense (p.R40H). Unaffected mothers are carriers = variant did not segregate with disease. The p.Arg40His mutation has 4 homozygotes in the population (gnomAD) and >350 heterozygotes - too common for a rare disorder.

PMID: 30622330 Li et al., 2019
Pedigree with a heterozygous missense variant in ACVR2B and heterotaxy. Family 1: p.(R383C) missense variant in ACVR2B was inherited from an affected parent, clear segregation of the variant with five affected individuals from three generations. The variant is not present in gnomAD v4, and it is classified as LP in ClinVar.

PMID: 35547246 Antony et al., 2022
Family SI-47 - proband with Situs inversus totalis had a heterozygous ACVR2B variant c.925C>T, p.Arg309Cys and a homozygous c.350A>G, p.Asp117Gly variant in CCDC39. CCDC39 is associated with recessive Ciliary dyskinesia, primary, 14, OMIM:613807. Effect of each variant is unclear.
Early onset or syndromic epilepsy v8.167 UNC13A Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, 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 BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v7.45 PPOX Achchuthan Shanmugasundram changed review comment from: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene has been updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v7.45 PPOX Achchuthan Shanmugasundram edited their review of gene: PPOX: Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric disorders - additional genes v7.37 ACVR2B Ida Ertmanska reviewed gene: ACVR2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 9916847, 21864452, 30622330; Phenotypes: Heterotaxy, visceral, 4, autosomal, OMIM:613751; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v8.167 UNC13A Arina Puzriakova Mode of inheritance for gene: UNC13A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v9.345 UNC13A Arina Puzriakova Mode of inheritance for gene: UNC13A was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v8.166 UNC13A Arina Puzriakova Tag Q1_26_MOI was removed from gene: UNC13A.
Intellectual disability v9.344 UNC13A Arina Puzriakova Tag Q1_26_MOI was removed from gene: UNC13A.
Intellectual disability v9.344 UNC13A Arina Puzriakova 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 BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v8.42 SPTSSA Arina Puzriakova Mode of inheritance for gene: SPTSSA was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Childhood onset hereditary spastic paraplegia v8.41 SPTSSA Arina Puzriakova Tag Q1_26_MOI was removed from gene: SPTSSA.
Childhood onset hereditary spastic paraplegia v8.41 SPTSSA Arina Puzriakova commented on gene: SPTSSA
Hereditary neuropathy v1.508 PPOX Arina Puzriakova Added comment: Comment on mode of inheritance: Monoallelic PPOX variants usually result in Variegate Porphyria limited to cutaneous manifestations, with disease onset in adolescence or adulthood. Biallelic variants are known to cause Variegate Porphyria with a more severe, early-onset phenotype - skin lesions, along with neurologic and/ or neurodevelopmental symptoms - including neuropathy. As reported by previous reviewers, 3 individuals with biallelic variants in PPOX presented with sensory neuropathy (PMID: 11286631 Kauppinen, 10870850 Corrigall, 8290408 Hift). Hence, the mode of inheritance has been set to 'BIALLELIC, autosomal or pseudoautosomal'.
Hereditary neuropathy v1.508 PPOX Arina Puzriakova Mode of inheritance for gene: PPOX was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v9.344 PPP2R2B Arina Puzriakova Added comment: Comment on mode of inheritance: Set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to allow detection of SNVs.
Intellectual disability v9.344 PPP2R2B Arina Puzriakova Mode of inheritance for gene: PPP2R2B was changed from Other to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v7.45 PPOX Arina Puzriakova Mode of inheritance for gene: PPOX was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v7.44 PPOX Arina Puzriakova Tag Q3_25_MOI was removed from gene: PPOX.
Severe microcephaly v8.36 LMNB2 Arina Puzriakova Mode of inheritance for gene: LMNB2 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Adult onset neurodegenerative disorder v8.20 ISCA-37478-Loss Arina Puzriakova Classified Region: ISCA-37478-Loss as Green List (high evidence)
Adult onset neurodegenerative disorder v8.20 ISCA-37478-Loss Arina Puzriakova Region: isca-37478-loss has been classified as Green List (High Evidence).
Adult onset neurodegenerative disorder v8.19 ISCA-37478-Loss Arina Puzriakova Tag curated_removed was removed from Region: ISCA-37478-Loss.
Adult onset neurodegenerative disorder v8.19 ISCA-37478-Loss Arina Puzriakova edited their review of Region: ISCA-37478-Loss: Added comment: The rating of this region has been updated to Green following NHS Genomic Medicine Service approval. Additional information: regions can be added to the panel as this clinical indication has now moved to WGS testing.; Changed rating: GREEN
Adult onset neurodegenerative disorder v8.19 ISCA-37446-Loss Arina Puzriakova changed review comment from: The rating of this region has been updated to Green following NHS Genomic Medicine Service approval. Additional information: regions can be added to the panel as this clinical indication has now moved to WGS testing. Other regions that were previously removed should also be reviewed. ; to: The rating of this region has been updated to Green following NHS Genomic Medicine Service approval. Additional information: regions can be added to the panel as this clinical indication has now moved to WGS testing.
Acute rhabdomyolysis v2.8 AMPD1 Arina Puzriakova Classified gene: AMPD1 as Red List (low evidence)
Acute rhabdomyolysis v2.8 AMPD1 Arina Puzriakova Gene: ampd1 has been classified as Red List (Low Evidence).
Acute rhabdomyolysis v2.7 AMPD1 Arina Puzriakova Tag Q3_25_expert_review was removed from gene: AMPD1.
Tag Q3_25_demote_red was removed from gene: AMPD1.
Acute rhabdomyolysis v2.7 AMPD1 Arina Puzriakova edited their review of gene: AMPD1: Added comment: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.; Changed rating: RED
Fetal anomalies v6.181 C1orf127 Ida Ertmanska Tag gene-checked was removed from gene: C1orf127.
Laterality disorders and isomerism v4.10 C1orf127 Ida Ertmanska Tag gene-checked was removed from gene: C1orf127.
Fetal anomalies v6.181 C16orf62 Ida Ertmanska Tag gene-checked was removed from gene: C16orf62.
Intellectual disability v9.343 CXorf56 Ida Ertmanska Tag gene-checked was removed from gene: CXorf56.
Fetal anomalies v6.181 EFCAB1 Ida Ertmanska Tag gene-checked was removed from gene: EFCAB1.
Respiratory ciliopathies including non-CF bronchiectasis v4.55 EFCAB1 Ida Ertmanska Tag gene-checked was removed from gene: EFCAB1.
Monogenic hearing loss v5.57 KIAA1024L Ida Ertmanska Tag gene-checked was removed from gene: KIAA1024L.
DDG2P v6.447 C11orf70 Ida Ertmanska Tag gene-checked was removed from gene: C11orf70.
Fetal anomalies v6.181 C11orf70 Ida Ertmanska Tag gene-checked was removed from gene: C11orf70.
Respiratory ciliopathies including non-CF bronchiectasis v4.55 C11orf70 Ida Ertmanska Tag gene-checked was removed from gene: C11orf70.
Laterality disorders and isomerism v4.10 C11orf70 Ida Ertmanska Tag new-gene-name tag was added to gene: C11orf70.
Laterality disorders and isomerism v4.10 C11orf70 Ida Ertmanska Tag new-gene-name was removed from gene: C11orf70.
Tag gene-checked was removed from gene: C11orf70.
Fetal anomalies v6.181 AL117258.1 Ida Ertmanska Tag gene-checked was removed from gene: AL117258.1.
Laterality disorders and isomerism v4.10 AL117258.1 Ida Ertmanska Tag gene-checked was removed from gene: AL117258.1.
Childhood onset dystonia, chorea or related movement disorder v7.18 PDE1B Ida Ertmanska Tag gene-checked tag was added to gene: PDE1B.
Intellectual disability v9.343 PDE1B Ida Ertmanska Tag gene-checked tag was added to gene: PDE1B.
Ataxia and cerebellar anomalies - narrow panel v8.72 PDE1B Ida Ertmanska Tag gene-checked tag was added to gene: PDE1B.
Mitochondrial disorders v9.46 PDE12 Ida Ertmanska Tag gene-checked tag was added to gene: PDE12.
Fetal anomalies v6.181 PDE12 Ida Ertmanska Tag gene-checked tag was added to gene: PDE12.
Possible mitochondrial disorder - nuclear genes v4.23 PDE12 Ida Ertmanska Tag gene-checked tag was added to gene: PDE12.
Likely inborn error of metabolism v8.100 PDE12 Ida Ertmanska Tag gene-checked tag was added to gene: PDE12.
Fetal anomalies v6.181 PDCD2 Ida Ertmanska Tag gene-checked tag was added to gene: PDCD2.
Monogenic short stature v1.31 PAPPA2 Ida Ertmanska Tag gene-checked was removed from gene: PAPPA2.
Paediatric disorders - additional genes v7.37 PAPPA2 Ida Ertmanska Tag gene-checked was removed from gene: PAPPA2.
DDG2P v6.447 NTNG2 Ida Ertmanska Tag gene-checked was removed from gene: NTNG2.
Intellectual disability v9.343 NTNG2 Ida Ertmanska Tag gene-checked was removed from gene: NTNG2.
Intellectual disability v9.343 NHLRC2 Ida Ertmanska Tag gene-checked was removed from gene: NHLRC2.
DDG2P v6.447 NHLRC2 Ida Ertmanska Tag gene-checked was removed from gene: NHLRC2.
DDG2P v6.447 NHLRC2 Ida Ertmanska Phenotypes for gene: NHLRC2 were changed from NHLRC2-related fibrosis, neurodegeneration, and cerebral angiomatosis, OMIM:618278 to FINCA syndrome OMIM:618278; NHLRC2-related fibrosis, neurodegeneration, and cerebral angiomatosis, OMIM:618278
Paediatric disorders - additional genes v7.37 NHLRC2 Ida Ertmanska Tag gene-checked was removed from gene: NHLRC2.
Rare anaemia v3.19 NHLRC2 Ida Ertmanska Tag gene-checked was removed from gene: NHLRC2.
Monogenic short stature v1.31 NHLRC2 Ida Ertmanska Tag gene-checked was removed from gene: NHLRC2.
Respiratory ciliopathies including non-CF bronchiectasis v4.55 NEK10 Ida Ertmanska Tag gene-checked was removed from gene: NEK10.
Paediatric or syndromic cardiomyopathy v7.99 NDUFAF8 Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotype updated 20 Mar 2026.
Paediatric or syndromic cardiomyopathy v7.99 NDUFAF8 Ida Ertmanska Phenotypes for gene: NDUFAF8 were changed from No OMIM phenotype to Mitochondrial complex I deficiency, nuclear type 34, OMIM:618776
DDG2P v6.446 NDUFAF8 Ida Ertmanska Tag gene-checked was removed from gene: NDUFAF8.
Mitochondrial disorders v9.46 NDUFAF8 Ida Ertmanska Tag gene-checked was removed from gene: NDUFAF8.
Fetal anomalies v6.181 NDUFAF8 Ida Ertmanska Tag gene-checked was removed from gene: NDUFAF8.
Likely inborn error of metabolism v8.100 NDUFAF8 Ida Ertmanska Tag gene-checked was removed from gene: NDUFAF8.
Mitochondrial disorder with complex I deficiency v3.19 NDUFAF8 Ida Ertmanska Tag gene-checked was removed from gene: NDUFAF8.
Possible mitochondrial disorder - nuclear genes v4.23 NDUFAF8 Ida Ertmanska Tag gene-checked was removed from gene: NDUFAF8.
Hereditary neuropathy v1.507 NDC1 Ida Ertmanska Phenotypes for gene: NDC1 were changed from demyelinating neuropathy; alacrima; achalasia to Neurodevelopmental disorder with achalasia, polyneuropathy, and alacrima, OMIM:621328; neurodevelopmental disorder with achalasia, polyneuropathy, and alacrima, MONDO:0979875
Hereditary neuropathy or pain disorder v7.44 NDC1 Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotype updated 20 Mar 2026.
Hereditary neuropathy or pain disorder v7.44 NDC1 Ida Ertmanska Phenotypes for gene: NDC1 were changed from demyelinating neuropathy; alacrima; achalasia to Neurodevelopmental disorder with achalasia, polyneuropathy, and alacrima, OMIM:621328; neurodevelopmental disorder with achalasia, polyneuropathy, and alacrima, MONDO:0979875
Hereditary neuropathy or pain disorder v7.43 NDC1 Ida Ertmanska Tag gene-checked was removed from gene: NDC1.
Haematological malignancies for rare disease v1.19 NAF1 Ida Ertmanska Tag gene-checked was removed from gene: NAF1.
Haematological malignancies cancer susceptibility v4.40 NAF1 Ida Ertmanska Tag gene-checked was removed from gene: NAF1.
Pulmonary fibrosis familial v1.9 NAF1 Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotype updated 20 Mar 2026.
Pulmonary fibrosis familial v1.9 NAF1 Ida Ertmanska Phenotypes for gene: NAF1 were changed from Pulmonary fibrosis-emphysema to Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7, OMIM:620365; pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7, MONDO:0957261
Pulmonary fibrosis familial v1.8 NAF1 Ida Ertmanska Tag gene-checked was removed from gene: NAF1.
Congenital myopathy v6.45 MYMX Ida Ertmanska Tag gene-checked was removed from gene: MYMX.
Early onset or syndromic epilepsy v8.166 MT-TK Ida Ertmanska Tag gene-checked tag was added to gene: MT-TK.
Intellectual disability v9.343 METTL5 Ida Ertmanska Tag gene-checked was removed from gene: METTL5.
DDG2P v6.446 METTL5 Ida Ertmanska Tag gene-checked was removed from gene: METTL5.
Severe microcephaly v8.35 METTL5 Ida Ertmanska Tag gene-checked was removed from gene: METTL5.
Intellectual disability v9.343 MARK2 Ida Ertmanska Added comment: Comment on phenotypes: Phenotype updated 20 Mar 2026.
Intellectual disability v9.343 MARK2 Ida Ertmanska Phenotypes for gene: MARK2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to Intellectual developmental disorder, autosomal dominant 76, OMIM:621285; intellectual developmental disorder, autosomal dominant 76, MONDO:0979575
Intellectual disability v9.342 MARK2 Ida Ertmanska Tag gene-checked was removed from gene: MARK2.
Early onset or syndromic epilepsy v8.166 MARK2 Ida Ertmanska Added comment: Comment on phenotypes: Phenotype updated 20 Mar 2026.
Early onset or syndromic epilepsy v8.166 MARK2 Ida Ertmanska Phenotypes for gene: MARK2 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to Intellectual developmental disorder, autosomal dominant 76, OMIM:621285; intellectual developmental disorder, autosomal dominant 76, MONDO:0979575
Early onset or syndromic epilepsy v8.165 MARK2 Ida Ertmanska Tag gene-checked was removed from gene: MARK2.
Intellectual disability v9.342 LRRC7 Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotype updated 20 Mar 2026.
Intellectual disability v9.342 LRRC7 Ida Ertmanska Phenotypes for gene: LRRC7 were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to Intellectual developmental disorder, autosomal dominant 77, OMIM:621415; intellectual developmental disorder, autosomal dominant 77, MONDO:0980748
Intellectual disability v9.341 LRRC7 Ida Ertmanska Tag gene-checked was removed from gene: LRRC7.
DDG2P v6.446 LRRC56 Ida Ertmanska Tag gene-checked was removed from gene: LRRC56.
Fetal anomalies v6.181 LRRC56 Ida Ertmanska Tag gene-checked was removed from gene: LRRC56.
Laterality disorders and isomerism v4.10 LRRC56 Ida Ertmanska Tag gene-checked was removed from gene: LRRC56.
Respiratory ciliopathies including non-CF bronchiectasis v4.55 LRRC56 Ida Ertmanska Tag gene-checked was removed from gene: LRRC56.
Early onset or syndromic epilepsy v8.165 LMBRD2 Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotype updated 20 Mar 2026.
Early onset or syndromic epilepsy v8.165 LMBRD2 Ida Ertmanska Phenotypes for gene: LMBRD2 were changed from Global developmental delay; Intellectual disability; Microcephaly; Seizures; Abnormality of nervous system morphology; Abnormality of the eye to Developmental delay with variable neurologic and brain abnormalities, OMIM:619694
Early onset or syndromic epilepsy v8.164 LMBRD2 Ida Ertmanska Tag gene-checked was removed from gene: LMBRD2.
Intellectual disability v9.341 LMBRD2 Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotype updated 20 Mar 2026.
Intellectual disability v9.341 LMBRD2 Ida Ertmanska Phenotypes for gene: LMBRD2 were changed from Global developmental delay; Intellectual disability; Microcephaly; Seizures; Abnormality of nervous system morphology; Abnormality of the eye to Developmental delay with variable neurologic and brain abnormalities, OMIM:619694
Intellectual disability v9.340 LMBRD2 Ida Ertmanska Tag gene-checked was removed from gene: LMBRD2.
Alveolar capillary dysplasia with misalignment of pulmonary veins v1.8 LINC01082 Ida Ertmanska Tag gene-checked tag was added to gene: LINC01082.
Fetal anomalies v6.181 LINC01082 Ida Ertmanska Tag gene-checked tag was added to gene: LINC01082.
Alveolar capillary dysplasia with misalignment of pulmonary veins v1.8 LINC01081 Ida Ertmanska Tag gene-checked tag was added to gene: LINC01081.
DDG2P v6.446 ZNRF3 Arina Puzriakova Tag gene-checked tag was added to gene: ZNRF3.
Fetal anomalies v6.181 LINC01081 Ida Ertmanska Tag gene-checked tag was added to gene: LINC01081.
Intellectual disability v9.340 ZNFX1 Arina Puzriakova Tag gene-checked was removed from gene: ZNFX1.
Early onset or syndromic epilepsy v8.164 ZNFX1 Arina Puzriakova Tag gene-checked was removed from gene: ZNFX1.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.88 ZNFX1 Arina Puzriakova Tag gene-checked was removed from gene: ZNFX1.
DDG2P v6.446 ZNF808 Arina Puzriakova Tag gene-checked was removed from gene: ZNF808.
Neonatal diabetes v5.20 ZNF808 Arina Puzriakova Phenotypes for gene: ZNF808 were changed from neonatal diabetes mellitus, MONDO:0016391; pancreatic agenesis, MONDO:0009832 to Pancreatic agenesis 3, OMIM:620991; neonatal diabetes mellitus, MONDO:0016391
DDG2P v6.446 KLHL20 Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotype updated 20 Mar 2026.
DDG2P v6.446 KLHL20 Ida Ertmanska Phenotypes for gene: KLHL20 were changed from KLHL20-related developmental disorder with seizures to KLHL20-related developmental disorder with seizures; Neurodevelopmental disorder with early-onset seizures, facial dysmorphism, and behavioral abnormalities, OMIM:621390
Neonatal diabetes v5.19 ZNF808 Arina Puzriakova Tag gene-checked was removed from gene: ZNF808.
DDG2P v6.445 KLHL20 Ida Ertmanska Tag gene-checked was removed from gene: KLHL20.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.88 ZNF341 Arina Puzriakova Tag gene-checked was removed from gene: ZNF341.
Early onset or syndromic epilepsy v8.164 KLHL20 Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotype updated 20 Mar 2026.
Early onset or syndromic epilepsy v8.164 KLHL20 Ida Ertmanska Phenotypes for gene: KLHL20 were changed from developmental disorder with intellectual disability, epilepsy, and autism spectrum disorder to Neurodevelopmental disorder with early-onset seizures, facial dysmorphism, and behavioral abnormalities, OMIM:621390
DDG2P v6.445 ZFYVE19 Arina Puzriakova Tag gene-checked was removed from gene: ZFYVE19.
Cholestasis v3.19 ZFYVE19 Arina Puzriakova Tag gene-checked was removed from gene: ZFYVE19.
Early onset or syndromic epilepsy v8.163 KLHL20 Ida Ertmanska Tag gene-checked was removed from gene: KLHL20.
Intellectual disability v9.340 ZFHX4 Arina Puzriakova Tag gene-checked tag was added to gene: ZFHX4.
Intellectual disability v9.340 KLHL20 Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotype updated 20 Mar 2026.
Intellectual disability v9.340 KLHL20 Ida Ertmanska Phenotypes for gene: KLHL20 were changed from developmental disorder with intellectual disability, epilepsy, and autism spectrum disorder to Neurodevelopmental disorder with early-onset seizures, facial dysmorphism, and behavioral abnormalities, OMIM:621390
DDG2P v6.445 ZFHX4 Arina Puzriakova Tag gene-checked tag was added to gene: ZFHX4.
Intellectual disability v9.339 KLHL20 Ida Ertmanska Tag gene-checked was removed from gene: KLHL20.
DDG2P v6.445 ZBTB11 Arina Puzriakova Tag gene-checked was removed from gene: ZBTB11.
Intellectual disability v9.339 ZBTB11 Arina Puzriakova Tag gene-checked was removed from gene: ZBTB11.
Severe microcephaly v8.35 YIF1B Arina Puzriakova Tag gene-checked was removed from gene: YIF1B.
Fetal anomalies v6.181 YIF1B Arina Puzriakova Tag gene-checked was removed from gene: YIF1B.
Early onset or syndromic epilepsy v8.163 YIF1B Arina Puzriakova Tag gene-checked was removed from gene: YIF1B.
Intellectual disability v9.339 YIF1B Arina Puzriakova Tag gene-checked was removed from gene: YIF1B.
Childhood onset dystonia, chorea or related movement disorder v7.18 YIF1B Arina Puzriakova Tag gene-checked was removed from gene: YIF1B.
DDG2P v6.445 KDM2B Ida Ertmanska Tag gene-checked was removed from gene: KDM2B.
DDG2P v6.445 XPO1 Arina Puzriakova Tag gene-checked tag was added to gene: XPO1.
DDG2P v6.445 KDM2B Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotype updated 20 Mar 2026.
DDG2P v6.445 KDM2B Ida Ertmanska Phenotypes for gene: KDM2B were changed from KDM2B-related neurodevelopmental disorder to KDM2B-related neurodevelopmental disorder; Neurodevelopmental disorder with congenital cardiac defects and variable renal and ocular abnormalities, OMIM:621474
Intellectual disability v9.339 WSB2 Arina Puzriakova Tag gene-checked tag was added to gene: WSB2.
Early onset or syndromic epilepsy v8.163 WSB2 Arina Puzriakova Tag gene-checked tag was added to gene: WSB2.
Ataxia and cerebellar anomalies - narrow panel v8.72 WSB2 Arina Puzriakova Tag gene-checked tag was added to gene: WSB2.
Fetal anomalies v6.181 WSB2 Arina Puzriakova Tag gene-checked tag was added to gene: WSB2.
Intellectual disability v9.339 KDM2B Ida Ertmanska Publications for gene: KDM2B were set to 36322151
Intellectual disability v9.338 KDM2B Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotype updated 20 Mar 2026.
Intellectual disability v9.338 KDM2B Ida Ertmanska Phenotypes for gene: KDM2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to Neurodevelopmental disorder with congenital cardiac defects and variable renal and ocular abnormalities, OMIM:621474
Intellectual disability v9.337 KDM2B Ida Ertmanska Tag gene-checked was removed from gene: KDM2B.
Fetal anomalies v6.181 KDM2B Ida Ertmanska Tag gene-checked was removed from gene: KDM2B.
Fetal anomalies v6.181 KDM2B Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotype updated 20 Mar 2026.
Fetal anomalies v6.181 KDM2B Ida Ertmanska Phenotypes for gene: KDM2B were changed from Neurodevelopmental disorder MONDO:0700092, KDM2B-related to Neurodevelopmental disorder with congenital cardiac defects and variable renal and ocular abnormalities, OMIM:621474
Fetal anomalies v6.180 KCNJ8 Ida Ertmanska Tag gene-checked tag was added to gene: KCNJ8.
DDG2P v6.444 KCNB2 Ida Ertmanska Tag gene-checked tag was added to gene: KCNB2.
Paediatric disorders - additional genes v7.37 ISL1 Ida Ertmanska Tag gene-checked tag was added to gene: ISL1.
Intellectual disability v9.337 HPDL Ida Ertmanska Tag gene-checked was removed from gene: HPDL.
Fetal anomalies v6.180 WDR91 Arina Puzriakova Tag gene-checked tag was added to gene: WDR91.
Fetal anomalies v6.180 WDR91 Arina Puzriakova Publications for gene: WDR91 were set to 32732226; 34028500; 28860274
DDG2P v6.444 HPDL Ida Ertmanska Phenotypes for gene: HPDL were changed from HPDL Neurodegenerative Disease to HPDL Neurodegenerative Disease; Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities OMIM:619026 Spastic paraplegia 83, autosomal recessive OMIM:619027
DDG2P v6.443 WDR83OS Arina Puzriakova Phenotypes for gene: WDR83OS were changed from MONDO:0975877; WDR83OS-related neurodevelopmental disorder with hypercholanemia to neurodevelopmental disorder with variable familial hypercholanemia, MONDO:0975877; WDR83OS-related neurodevelopmental disorder with hypercholanemia
DDG2P v6.442 HPDL Ida Ertmanska Tag gene-checked was removed from gene: HPDL.
Early onset or syndromic epilepsy v8.163 HPDL Ida Ertmanska Tag gene-checked was removed from gene: HPDL.
Possible mitochondrial disorder - nuclear genes v4.23 HPDL Ida Ertmanska Tag gene-checked was removed from gene: HPDL.
Intellectual disability v9.337 WDR83OS Arina Puzriakova Tag gene-checked was removed from gene: WDR83OS.
DDG2P v6.442 WDR83OS Arina Puzriakova Tag gene-checked was removed from gene: WDR83OS.
Mitochondrial disorders v9.46 HPDL Ida Ertmanska Tag gene-checked was removed from gene: HPDL.
Likely inborn error of metabolism v8.100 HPDL Ida Ertmanska Tag gene-checked was removed from gene: HPDL.
Hereditary neuropathy or pain disorder v7.43 HPDL Ida Ertmanska Tag gene-checked was removed from gene: HPDL.
DDG2P v6.442 WDR83OS Arina Puzriakova Tag gene-checked tag was added to gene: WDR83OS.
Childhood onset hereditary spastic paraplegia v8.41 HPDL Ida Ertmanska Tag gene-checked was removed from gene: HPDL.
Severe microcephaly v8.35 HPDL Ida Ertmanska Tag gene-checked was removed from gene: HPDL.
DDG2P v6.442 WDR44 Arina Puzriakova Tag gene-checked tag was added to gene: WDR44.
White matter disorders and cerebral calcification - narrow panel v7.19 HPDL Ida Ertmanska Tag gene-checked was removed from gene: HPDL.
DDG2P v6.442 IKZF2 Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotypes updated 20 Mar 2026.
DDG2P v6.442 IKZF2 Ida Ertmanska Phenotypes for gene: IKZF2 were changed from IKZF2-related ICHAD syndrome to Immunodysregulation with variable immunodeficiency and autoimmunity, OMIM:621233; Immunodysregulation, craniofacial anomalies, hearing impairment, athelia, and developmental delay, OMIM:621234
Early onset or syndromic epilepsy v8.163 WDR37 Arina Puzriakova Phenotypes for gene: WDR37 were changed from Global developmental delay; Intellectual disability; Seizures; Abnormality of the eye; Abnormality of nervous system morphology; Hearing abnormality; Abnormality of the cardiovascular system; Abnormality of the skeletal system; Abnormality of the genitourinary system; Neurooculocardiogenitourinary syndrome, OMIM:618652 to Neurooculocardiogenitourinary syndrome, OMIM:618652
Intellectual disability v9.337 WDR37 Arina Puzriakova Phenotypes for gene: WDR37 were changed from Global developmental delay; Intellectual disability; Seizures; Abnormality of the eye; Abnormality of nervous system morphology; Hearing abnormality; Abnormality of the cardiovascular system; Abnormality of the skeletal system; Abnormality of the genitourinary system; Neurooculocardiogenitourinary syndrome, OMIM:618652 to Neurooculocardiogenitourinary syndrome, OMIM:618652
Fetal anomalies v6.179 IKZF2 Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotypes updated 20 Mar 2026.
Fetal anomalies v6.179 IKZF2 Ida Ertmanska Phenotypes for gene: IKZF2 were changed from Immunodysregulation, craniofacial anomalies, hearing impairment, athelia and developmental delay, OMIM:621234 to Immunodysregulation with variable immunodeficiency and autoimmunity, OMIM:621233; Immunodysregulation, craniofacial anomalies, hearing impairment, athelia, and developmental delay, OMIM:621234
Structural eye disease v4.40 WDR37 Arina Puzriakova Tag gene-checked was removed from gene: WDR37.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.88 IKZF2 Ida Ertmanska Tag gene-checked was removed from gene: IKZF2.
Intellectual disability v9.336 WDR37 Arina Puzriakova Tag gene-checked was removed from gene: WDR37.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.88 IKZF2 Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotypes updated 20 Mar 2026.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.88 IKZF2 Ida Ertmanska Phenotypes for gene: IKZF2 were changed from combined immunodeficiency; thrush; mucosal ulcers; chronic lymphoadenopathy; reduced MAIT cells to Immunodysregulation with variable immunodeficiency and autoimmunity, OMIM:621233; Immunodysregulation, craniofacial anomalies, hearing impairment, athelia, and developmental delay, OMIM:621234
Early onset or syndromic epilepsy v8.162 WDR37 Arina Puzriakova Tag gene-checked was removed from gene: WDR37.
DDG2P v6.441 WDR37 Arina Puzriakova Tag gene-checked was removed from gene: WDR37.
Fetal anomalies v6.178 WDR37 Arina Puzriakova Tag gene-checked was removed from gene: WDR37.
Severe microcephaly v8.35 WDR37 Arina Puzriakova Tag gene-checked was removed from gene: WDR37.
Paediatric disorders - additional genes v7.37 WBP11 Arina Puzriakova Tag gene-checked was removed from gene: WBP11.
Fetal anomalies v6.178 WBP11 Arina Puzriakova Tag gene-checked was removed from gene: WBP11.
Skeletal dysplasia v8.38 WBP11 Arina Puzriakova Tag gene-checked was removed from gene: WBP11.
Retinal disorders v8.100 USP45 Arina Puzriakova Added comment: Comment on phenotypes: OMIM phenotype accessed on 20-03-2026
Retinal disorders v8.100 USP45 Arina Puzriakova Phenotypes for gene: USP45 were changed from Lebers congenital amaurosis; retinal dystrophy; ?Leber congenital amaurosis 19, OMIMM:618513 to ?Leber congenital amaurosis 19, OMIM:618513
Retinal disorders v8.99 USP45 Arina Puzriakova Tag gene-checked was removed from gene: USP45.
Intellectual disability v9.336 UPF1 Arina Puzriakova Tag gene-checked tag was added to gene: UPF1.
Fetal anomalies v6.178 HMGB1 Ida Ertmanska Publications for gene: HMGB1 were set to 34164801
Fetal anomalies v6.177 HMGB1 Ida Ertmanska Tag gene-checked tag was added to gene: HMGB1.
Renal ciliopathies v4.11 TXNDC15 Arina Puzriakova Tag gene-checked was removed from gene: TXNDC15.
Neurological ciliopathies v6.15 TXNDC15 Arina Puzriakova Tag gene-checked was removed from gene: TXNDC15.
Rare multisystem ciliopathy disorders v1.180 TXNDC15 Arina Puzriakova Tag gene-checked was removed from gene: TXNDC15.
Fetal anomalies v6.177 TXNDC15 Arina Puzriakova Tag gene-checked was removed from gene: TXNDC15.
Limb disorders v7.22 TXNDC15 Arina Puzriakova Tag gene-checked was removed from gene: TXNDC15.
Intellectual disability v9.336 HECTD4 Ida Ertmanska Tag gene-checked was removed from gene: HECTD4.
Early onset or syndromic epilepsy v8.162 HECTD4 Ida Ertmanska Tag gene-checked was removed from gene: HECTD4.
Intellectual disability v9.336 TUBGCP2 Arina Puzriakova Tag gene-checked was removed from gene: TUBGCP2.
Early onset or syndromic epilepsy v8.162 TUBGCP2 Arina Puzriakova Tag gene-checked was removed from gene: TUBGCP2.
DDG2P v6.441 HECTD4 Ida Ertmanska Tag gene-checked was removed from gene: HECTD4.
DDG2P v6.441 TUBGCP2 Arina Puzriakova Tag gene-checked was removed from gene: TUBGCP2.
Fetal anomalies v6.177 TUBGCP2 Arina Puzriakova Tag gene-checked was removed from gene: TUBGCP2.
Severe microcephaly v8.35 TUBGCP2 Arina Puzriakova Tag gene-checked was removed from gene: TUBGCP2.
Malformations of cortical development v7.39 TUBGCP2 Arina Puzriakova Tag gene-checked was removed from gene: TUBGCP2.
Fetal anomalies v6.177 HECTD4 Ida Ertmanska Tag gene-checked was removed from gene: HECTD4.
Childhood onset hereditary spastic paraplegia v8.41 HECTD4 Ida Ertmanska Tag gene-checked was removed from gene: HECTD4.
Malformations of cortical development v7.39 HECTD4 Ida Ertmanska Tag gene-checked was removed from gene: HECTD4.
Severe microcephaly v8.35 TTC5 Arina Puzriakova Tag gene-checked was removed from gene: TTC5.
DDG2P v6.441 TTC5 Arina Puzriakova Tag gene-checked was removed from gene: TTC5.
Intellectual disability v9.336 TTC5 Arina Puzriakova Tag gene-checked was removed from gene: TTC5.
DDG2P v6.441 HEATR5B Ida Ertmanska Tag gene-checked tag was added to gene: HEATR5B.
Intellectual disability v9.336 HEATR5B Ida Ertmanska Tag gene-checked tag was added to gene: HEATR5B.
Early onset or syndromic epilepsy v8.162 HEATR5B Ida Ertmanska Tag gene-checked tag was added to gene: HEATR5B.
Mitochondrial disorders v9.46 TRIT1 Arina Puzriakova Tag gene-checked was removed from gene: TRIT1.
Intellectual disability v9.336 TRIT1 Arina Puzriakova Tag gene-checked was removed from gene: TRIT1.
Early onset or syndromic epilepsy v8.162 TRIT1 Arina Puzriakova Tag gene-checked was removed from gene: TRIT1.
DDG2P v6.441 TRIT1 Arina Puzriakova Tag gene-checked was removed from gene: TRIT1.
Fetal anomalies v6.177 TRIT1 Arina Puzriakova Tag gene-checked was removed from gene: TRIT1.
Possible mitochondrial disorder - nuclear genes v4.23 TRIT1 Arina Puzriakova Tag gene-checked was removed from gene: TRIT1.
Likely inborn error of metabolism v8.100 TRIT1 Arina Puzriakova Tag gene-checked was removed from gene: TRIT1.
Ataxia and cerebellar anomalies - narrow panel v8.72 HEATR5B Ida Ertmanska Tag gene-checked tag was added to gene: HEATR5B.
DDG2P v6.441 TRIM71 Arina Puzriakova Phenotypes for gene: TRIM71 were changed from TRIM71-related neurodevelopmental disorder with ventriculomegaly and hydrocephalus; MONDO:0032862; OMIM:618667.0 to TRIM71-related neurodevelopmental disorder with ventriculomegaly and hydrocephalus; hydrocephalus, congenital communicating, 1, MONDO:0032862; Hydrocephalus, congenital communicating, 1, OMIM:618667
DDG2P v6.440 GTF3C5 Ida Ertmanska Tag gene-checked tag was added to gene: GTF3C5.
Fetal anomalies v6.177 TRIM71 Arina Puzriakova Tag gene-checked was removed from gene: TRIM71.
Hydrocephalus v5.12 TRIM71 Arina Puzriakova Tag gene-checked was removed from gene: TRIM71.
Paediatric disorders - additional genes v7.37 GREB1L Ida Ertmanska Phenotypes for gene: GREB1L were changed from Deafness, autosomal dominant 80 OMIM:619274; deafness, autosomal dominant 80, MONDO:0030998; Renal hypodysplasia/aplasia 3, OMIM:617805 Renal agenesis, MONDO:0018470 to Deafness, autosomal dominant 80 OMIM:619274; deafness, autosomal dominant 80, MONDO:0030998; Renal hypodysplasia/aplasia 3, OMIM:617805; Renal agenesis, MONDO:0018470
Monogenic hearing loss v5.57 FOXI1 Barbara Vona reviewed gene: FOXI1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 41833579; Phenotypes: Hearing loss with Mondini malformation and and enlarged vestibular aqueduct; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Paediatric disorders - additional genes v7.36 GREB1L Ida Ertmanska Phenotypes for gene: GREB1L were changed from CAKUT; Renal hypodysplasia/aplasia 3, 617805; inner ear malformations to Deafness, autosomal dominant 80 OMIM:619274; deafness, autosomal dominant 80, MONDO:0030998; Renal hypodysplasia/aplasia 3, OMIM:617805 Renal agenesis, MONDO:0018470
Wilms tumour with features suggestive of predisposition v1.5 TRIM28 Arina Puzriakova Added comment: Comment on phenotypes: OMIM phenotype accessed on 20-03-2026
Wilms tumour with features suggestive of predisposition v1.5 TRIM28 Arina Puzriakova Phenotypes for gene: TRIM28 were changed from Wilms tumor; Familial Wilms tumor to Wilms tumor 7, OMIM:621332
Childhood solid tumours v5.10 TRIM28 Arina Puzriakova Added comment: Comment on phenotypes: OMIM phenotype accessed on 20-03-2026
Childhood solid tumours v5.10 TRIM28 Arina Puzriakova Phenotypes for gene: TRIM28 were changed from Familial Wilms tumor; Wilms tumour to Wilms tumor 7, OMIM:621332
Wilms tumour with features suggestive of predisposition v1.4 TRIM28 Arina Puzriakova Tag gene-checked was removed from gene: TRIM28.
Childhood solid tumours v5.9 TRIM28 Arina Puzriakova Tag gene-checked was removed from gene: TRIM28.
Intellectual disability v9.336 TRA2B Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v9.336 TRA2B Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v9.336 TRA2B Achchuthan Shanmugasundram Deleted their comment
Monogenic hearing loss v5.57 GREB1L Ida Ertmanska Tag gene-checked was removed from gene: GREB1L.
DDG2P v6.440 GREB1L Ida Ertmanska Tag gene-checked was removed from gene: GREB1L.
Fetal anomalies v6.177 GREB1L Ida Ertmanska Tag gene-checked was removed from gene: GREB1L.
Intellectual disability v9.336 TRA2B Arina Puzriakova Added comment: Comment on phenotypes: OMIM phenotype accessed on 20-03-2026
Intellectual disability v9.336 TRA2B Arina Puzriakova Phenotypes for gene: TRA2B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to Ramond-Elliott neurodevelopmental syndrome, OMIM:621421
Early onset or syndromic epilepsy v8.162 TRA2B Arina Puzriakova Added comment: Comment on phenotypes: OMIM phenotype accessed on 20-03-2026
Early onset or syndromic epilepsy v8.162 TRA2B Arina Puzriakova Phenotypes for gene: TRA2B were changed from neurodevelopmental disorder, MONDO:0700092; epilepsy, MONDO:0005027 to Ramond-Elliott neurodevelopmental syndrome, OMIM:621421
CAKUT v1.182 GREB1L Ida Ertmanska Tag gene-checked was removed from gene: GREB1L.
CAKUT v1.182 GREB1L Ida Ertmanska Phenotypes for gene: GREB1L were changed from Renal hypodysplasia/aplasia 3, 617805 to Renal hypodysplasia/aplasia 3, OMIM:617805 Renal agenesis, MONDO:0018470
Severe microcephaly v8.35 TRA2B Arina Puzriakova Added comment: Comment on phenotypes: OMIM phenotype accessed on 20-03-2026
Severe microcephaly v8.35 TRA2B Arina Puzriakova Phenotypes for gene: TRA2B were changed from neurodevelopmental disorder, MONDO:0700092; microcephaly, MONDO:0001149 to Ramond-Elliott neurodevelopmental syndrome, OMIM:621421
Paediatric disorders - additional genes v7.35 GREB1L Ida Ertmanska Tag gene-checked was removed from gene: GREB1L.
Intellectual disability v9.335 TRA2B Arina Puzriakova Tag gene-checked was removed from gene: TRA2B.
Early onset or syndromic epilepsy v8.161 TRA2B Arina Puzriakova Tag gene-checked was removed from gene: TRA2B.
Fetal anomalies v6.177 GPKOW Ida Ertmanska Tag gene-checked tag was added to gene: GPKOW.
DDG2P v6.440 TRA2B Arina Puzriakova Tag gene-checked was removed from gene: TRA2B.
Severe microcephaly v8.34 GPKOW Ida Ertmanska Tag gene-checked tag was added to gene: GPKOW.
Paediatric disorders - additional genes v7.35 GPKOW Ida Ertmanska Tag gene-checked tag was added to gene: GPKOW.
Intellectual disability v9.335 TMEM94 Arina Puzriakova Tag gene-checked was removed from gene: TMEM94.
DDG2P v6.440 TMEM94 Arina Puzriakova Tag gene-checked was removed from gene: TMEM94.
Fetal anomalies v6.177 TMEM94 Arina Puzriakova Tag gene-checked was removed from gene: TMEM94.
Retinal disorders v8.99 GPATCH11 Ida Ertmanska Tag gene-checked tag was added to gene: GPATCH11.
Intellectual disability v9.335 GPATCH11 Ida Ertmanska Tag gene-checked tag was added to gene: GPATCH11.
Intellectual disability v9.335 TMEM63C Arina Puzriakova Added comment: Comment on phenotypes: OMIM phenotype accessed on 20-03-2026
Intellectual disability v9.335 TMEM63C Arina Puzriakova Phenotypes for gene: TMEM63C were changed from hereditary spastic paraplegia, MONDO:0019064 to Spastic paraplegia 87, autosomal recessive, OMIM:619966
Childhood onset hereditary spastic paraplegia v8.41 TMEM63C Arina Puzriakova Added comment: Comment on phenotypes: OMIM phenotype accessed on 20-03-2026
Childhood onset hereditary spastic paraplegia v8.41 TMEM63C Arina Puzriakova Phenotypes for gene: TMEM63C were changed from hereditary spastic paraplegia, MONDO:0019064 to Spastic paraplegia 87, autosomal recessive, OMIM:619966
Fetal anomalies v6.177 GINS3 Ida Ertmanska Tag gene-checked tag was added to gene: GINS3.
DDG2P v6.440 TMEM63C Arina Puzriakova Tag gene-checked was removed from gene: TMEM63C.
Intellectual disability v9.334 TMEM63C Arina Puzriakova Tag gene-checked was removed from gene: TMEM63C.
Hereditary ataxia with onset in adulthood v8.30 GDAP2 Ida Ertmanska Tag gene-checked was removed from gene: GDAP2.
Childhood onset hereditary spastic paraplegia v8.40 TMEM63C Arina Puzriakova Tag gene-checked was removed from gene: TMEM63C.
Intellectual disability v9.334 TMEM63B Arina Puzriakova Added comment: Comment on phenotypes: OMIM phenotype accessed on 20-03-2026
Intellectual disability v9.334 TMEM63B Arina Puzriakova Phenotypes for gene: TMEM63B were changed from developmental and epileptic encephalopathy, MONDO:0100062 to Developmental and epileptic encephalopathy 118, OMIM:621250
Early onset or syndromic epilepsy v8.161 TMEM63B Arina Puzriakova Added comment: Comment on phenotypes: OMIM phenotype accessed on 20-03-2026
Early onset or syndromic epilepsy v8.161 TMEM63B Arina Puzriakova Phenotypes for gene: TMEM63B were changed from developmental and epileptic encephalopathy, MONDO:0100062 to Developmental and epileptic encephalopathy 118, OMIM:621250
Hereditary ataxia with onset in adulthood v8.30 GDAP2 Ida Ertmanska Tag gene-checked tag was added to gene: GDAP2.
Intellectual disability v9.333 TMEM63B Arina Puzriakova Tag gene-checked was removed from gene: TMEM63B.
Early onset or syndromic epilepsy v8.160 TMEM63B Arina Puzriakova Tag gene-checked was removed from gene: TMEM63B.
DDG2P v6.440 TMEM63B Arina Puzriakova Tag gene-checked was removed from gene: TMEM63B.
DDG2P v6.440 GABRA4 Ida Ertmanska Tag gene-checked tag was added to gene: GABRA4.
DDG2P v6.440 TMEM63A Arina Puzriakova Tag gene-checked was removed from gene: TMEM63A.
White matter disorders and cerebral calcification - narrow panel v7.19 TMEM63A Arina Puzriakova Tag gene-checked was removed from gene: TMEM63A.
Skeletal dysplasia v8.38 TMEM251 Arina Puzriakova Tag gene-checked was removed from gene: TMEM251.
DDG2P v6.440 TMEM251 Arina Puzriakova Tag gene-checked was removed from gene: TMEM251.
Rare syndromic craniosynostosis or isolated multisuture synostosis v6.4 TMEM251 Arina Puzriakova Tag gene-checked was removed from gene: TMEM251.
Intellectual disability v9.333 FRYL Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotype added 20 Mar 2026.
Intellectual disability v9.333 FRYL Ida Ertmanska Phenotypes for gene: FRYL were changed from Neurodevelopmental disorder, MONDO:0700092 to Pan-Chung-Bellen syndrome, OMIM:621049; Pan-Chung-Bellen syndrome, MONDO:0975953
Intellectual disability v9.332 FRYL Ida Ertmanska Tag gene-checked was removed from gene: FRYL.
DDG2P v6.440 FRYL Ida Ertmanska Tag gene-checked was removed from gene: FRYL.
Fetal anomalies v6.177 FRYL Ida Ertmanska Tag gene-checked was removed from gene: FRYL.
Fetal anomalies v6.177 FRYL Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotype updated 20 Mar 2026.
Fetal anomalies v6.177 FRYL Ida Ertmanska Phenotypes for gene: FRYL were changed from Neurodevelopmental disorder, MONDO:0700092, FRYL-related to Pan-Chung-Bellen syndrome, OMIM:621049; Pan-Chung-Bellen syndrome, MONDO:0975953
DDG2P v6.440 FRYL Ida Ertmanska Phenotypes for gene: FRYL were changed from Pan-Chung-Bellen syndrome, OMIM:621049; MONDO:0975953; FRYL-related neurodevelopmental disorder with dysmorphic facial features, with or without congenital abnormalities to Pan-Chung-Bellen syndrome, OMIM:621049; Pan-Chung-Bellen syndrome, MONDO:0975953
DDG2P v6.439 FRYL Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotype added 20 Mar 2026.
DDG2P v6.439 FRYL Ida Ertmanska Phenotypes for gene: FRYL were changed from MONDO:0975953; FRYL-related neurodevelopmental disorder with dysmorphic facial features, with or without congenital abnormalities to Pan-Chung-Bellen syndrome, OMIM:621049; MONDO:0975953; FRYL-related neurodevelopmental disorder with dysmorphic facial features, with or without congenital abnormalities
Intellectual disability v9.332 TMEM222 Arina Puzriakova Added comment: Comment on phenotypes: OMIM phenotype accessed on 20-03-2026
Intellectual disability v9.332 TMEM222 Arina Puzriakova Phenotypes for gene: TMEM222 were changed from Motor delay; Delayed speech and language development; Intellectual disability; Generalized hypotonia; Broad-based gait; Abnormality of nervous system morphology; Seizures; Microcephaly; Behavioral abnormality to Neurodevelopmental disorder with motor and speech delay and behavioral abnormalities, OMIM:619470
Early onset or syndromic epilepsy v8.160 TMEM222 Arina Puzriakova Added comment: Comment on phenotypes: OMIM phenotype accessed on 20-03-2026
Early onset or syndromic epilepsy v8.160 TMEM222 Arina Puzriakova Phenotypes for gene: TMEM222 were changed from Motor delay; Delayed speech and language development; Intellectual disability; Generalized hypotonia; Broad-based gait; Abnormality of nervous system morphology; Seizures; Microcephaly; Behavioral abnormality to Neurodevelopmental disorder with motor and speech delay and behavioral abnormalities, OMIM:619470
DDG2P v6.438 TMEM222 Arina Puzriakova Tag gene-checked was removed from gene: TMEM222.
Intellectual disability v9.331 TMEM222 Arina Puzriakova Tag gene-checked was removed from gene: TMEM222.
Early onset or syndromic epilepsy v8.159 TMEM222 Arina Puzriakova Tag gene-checked was removed from gene: TMEM222.
Fetal anomalies v6.176 TMEM17 Arina Puzriakova Tag gene-checked was removed from gene: TMEM17.
Neurological ciliopathies v6.15 TMEM218 Arina Puzriakova Tag gene-checked was removed from gene: TMEM218.
Ophthalmological ciliopathies v5.15 TMEM218 Arina Puzriakova Tag gene-checked was removed from gene: TMEM218.
Rare multisystem ciliopathy disorders v1.180 TMEM218 Arina Puzriakova Tag gene-checked was removed from gene: TMEM218.
Retinal disorders v8.99 TMEM218 Arina Puzriakova Tag gene-checked was removed from gene: TMEM218.
DDG2P v6.438 TMEM218 Arina Puzriakova Tag gene-checked was removed from gene: TMEM218.
Fetal anomalies v6.176 TMEM218 Arina Puzriakova Tag gene-checked was removed from gene: TMEM218.
Fetal anomalies v6.176 TMEM17 Arina Puzriakova Publications for gene: TMEM17 were set to
Fetal anomalies v6.175 TMEM17 Arina Puzriakova Phenotypes for gene: TMEM17 were changed from Ciliopathy to ciliopathy, MONDO:0005308
Fetal anomalies v6.174 TMEM17 Arina Puzriakova Tag gene-checked tag was added to gene: TMEM17.
Early onset or syndromic epilepsy v8.159 TMEM167A Arina Puzriakova Tag gene-checked tag was added to gene: TMEM167A.
Fetal anomalies v6.174 TMEM167A Arina Puzriakova Tag gene-checked tag was added to gene: TMEM167A.
Severe microcephaly v8.34 TMEM167A Arina Puzriakova Tag gene-checked tag was added to gene: TMEM167A.
Neonatal diabetes v5.19 TMEM167A Arina Puzriakova Tag gene-checked tag was added to gene: TMEM167A.
Fetal anomalies v6.174 TMEM167A Arina Puzriakova Publications for gene: TMEM167A were set to
Fetal anomalies v6.173 TMEM167A Arina Puzriakova Phenotypes for gene: TMEM167A were changed from Microcephaly, epilepsy and diabetes syndrome to Microcephaly, epilepsy, and diabetes syndrome, MONDO:0100328
Childhood onset dystonia, chorea or related movement disorder v7.18 TMEM151A Arina Puzriakova Tag gene-checked was removed from gene: TMEM151A.
Ataxia and cerebellar anomalies - narrow panel v8.72 THG1L Arina Puzriakova Tag gene-checked was removed from gene: THG1L.
Intellectual disability v9.331 TBC1D8B Arina Puzriakova Tag gene-checked was removed from gene: TBC1D8B.
Proteinuric renal disease v5.9 TBC1D8B Arina Puzriakova Tag gene-checked was removed from gene: TBC1D8B.
DDG2P v6.438 TBC1D2B Arina Puzriakova Tag gene-checked was removed from gene: TBC1D2B.
Early onset or syndromic epilepsy v8.159 TBC1D2B Arina Puzriakova Tag gene-checked was removed from gene: TBC1D2B.
Intellectual disability v9.331 TBC1D2B Arina Puzriakova Tag gene-checked was removed from gene: TBC1D2B.
Intellectual disability v9.331 SVBP Arina Puzriakova Tag gene-checked was removed from gene: SVBP.
Severe microcephaly v8.34 SVBP Arina Puzriakova Tag gene-checked was removed from gene: SVBP.
Ataxia and cerebellar anomalies - narrow panel v8.72 SVBP Arina Puzriakova Tag gene-checked was removed from gene: SVBP.
Childhood onset dystonia, chorea or related movement disorder v7.18 SPATA5L1 Arina Puzriakova Tag gene-checked was removed from gene: SPATA5L1.
Intellectual disability v9.331 SPATA5L1 Arina Puzriakova Tag gene-checked was removed from gene: SPATA5L1.
Early onset or syndromic epilepsy v8.159 SPATA5L1 Arina Puzriakova Tag gene-checked was removed from gene: SPATA5L1.
Monogenic hearing loss v5.57 SPATA5L1 Arina Puzriakova Tag gene-checked was removed from gene: SPATA5L1.
DDG2P v6.438 SPATA5L1 Arina Puzriakova Tag gene-checked was removed from gene: SPATA5L1.
Childhood onset hereditary spastic paraplegia v8.40 SPATA5L1 Arina Puzriakova Tag gene-checked was removed from gene: SPATA5L1.
Severe microcephaly v8.34 SPATA5L1 Arina Puzriakova Tag gene-checked was removed from gene: SPATA5L1.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.87 SNORA31 Arina Puzriakova Added comment: Comment on phenotypes: OMIM phenotype accessed on 20-03-2026
Primary immunodeficiency or monogenic inflammatory bowel disease v8.87 SNORA31 Arina Puzriakova Phenotypes for gene: SNORA31 were changed from Herpes simplex encephalitis to {Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 10}, OMIM:619396
Primary immunodeficiency or monogenic inflammatory bowel disease v8.86 SNORA31 Arina Puzriakova Tag gene-checked was removed from gene: SNORA31.
DDG2P v6.438 SEPHS1 Arina Puzriakova Tag gene-checked was removed from gene: SEPHS1.
Intellectual disability v9.331 SEPHS1 Arina Puzriakova Tag gene-checked was removed from gene: SEPHS1.
Retinal disorders v8.99 SAMD7 Arina Puzriakova Tag gene-checked was removed from gene: SAMD7.
Fetal anomalies v6.172 RREB1 Arina Puzriakova Publications for gene: RREB1 were set to
Fetal anomalies v6.171 RREB1 Arina Puzriakova Phenotypes for gene: RREB1 were changed from Rasopathy, mild dysmorphisms, congenital heart disease, genitourinary malformations, dental anomalies, and developmental delay to RASopathy, MONDO:0021060; Rasopathy, mild dysmorphisms, congenital heart disease, genitourinary malformations, dental anomalies, and developmental delay
Fetal anomalies v6.170 RREB1 Arina Puzriakova Tag gene-checked tag was added to gene: RREB1.
Intellectual disability v9.331 RNU7-1 Arina Puzriakova Added comment: Comment on phenotypes: OMIM phenotype accessed on 20-03-2026
Intellectual disability v9.331 RNU7-1 Arina Puzriakova Phenotypes for gene: RNU7-1 were changed from Aicardi–Goutières syndrome-like; Type I interferonopathy to Aicardi-Goutieres syndrome 9, OMIM:619487; Type I interferonopathy
Fetal anomalies v6.170 RNU7-1 Arina Puzriakova Added comment: Comment on phenotypes: OMIM phenotype accessed on 20-03-2026
Fetal anomalies v6.170 RNU7-1 Arina Puzriakova Phenotypes for gene: RNU7-1 were changed from Aicardi-Goutieres syndrome 9 OMIM:619487 to Aicardi-Goutieres syndrome 9, OMIM:619487; Type I interferonopathy
Childhood onset dystonia, chorea or related movement disorder v7.18 RNU7-1 Arina Puzriakova Added comment: Comment on phenotypes: OMIM phenotype accessed on 20-03-2026
Childhood onset dystonia, chorea or related movement disorder v7.18 RNU7-1 Arina Puzriakova Phenotypes for gene: RNU7-1 were changed from Aicardi–Goutières syndrome-like; Type I interferonopathy to Aicardi-Goutieres syndrome 9, OMIM:619487; Type I interferonopathy
Childhood onset hereditary spastic paraplegia v8.40 RNU7-1 Arina Puzriakova Added comment: Comment on phenotypes: OMIM phenotype accessed on 20-03-2026
Childhood onset hereditary spastic paraplegia v8.40 RNU7-1 Arina Puzriakova Phenotypes for gene: RNU7-1 were changed from Type I interferonopathy; Aicardi-Goutières syndrome to Aicardi-Goutieres syndrome 9, OMIM:619487; Type I interferonopathy
White matter disorders and cerebral calcification - narrow panel v7.19 RNU7-1 Arina Puzriakova commented on gene: RNU7-1: Comment on phenotypes: OMIM phenotype accessed on 20-03-2026
Childhood onset dystonia, chorea or related movement disorder v7.17 RNU7-1 Arina Puzriakova Tag gene-checked was removed from gene: RNU7-1.
Intellectual disability v9.330 RNU7-1 Arina Puzriakova Tag gene-checked was removed from gene: RNU7-1.
Fetal anomalies v6.169 RNU7-1 Arina Puzriakova Tag gene-checked was removed from gene: RNU7-1.
Childhood onset hereditary spastic paraplegia v8.39 RNU7-1 Arina Puzriakova Tag gene-checked was removed from gene: RNU7-1.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.86 RNU7-1 Arina Puzriakova Added comment: Comment on phenotypes: OMIM phenotype accessed on 20-03-2026
Primary immunodeficiency or monogenic inflammatory bowel disease v8.86 RNU7-1 Arina Puzriakova Phenotypes for gene: RNU7-1 were changed from Aicardi-Goutières syndrome-like; Type 1 interferonopathy to Aicardi-Goutieres syndrome 9, OMIM:619487; Type I interferonopathy
Primary immunodeficiency or monogenic inflammatory bowel disease v8.85 RNU7-1 Arina Puzriakova Tag gene-checked was removed from gene: RNU7-1.
White matter disorders and cerebral calcification - narrow panel v7.19 RNU7-1 Arina Puzriakova Phenotypes for gene: RNU7-1 were changed from Aicardi–Goutières syndrome-like; Type I interferonopathy to Aicardi-Goutieres syndrome 9, OMIM:619487; Type I interferonopathy
White matter disorders and cerebral calcification - narrow panel v7.18 RNU7-1 Arina Puzriakova Tag gene-checked was removed from gene: RNU7-1.
Intellectual disability v9.330 RNU5B-1 Arina Puzriakova Tag gene-checked was removed from gene: RNU5B-1.
Early onset or syndromic epilepsy v8.159 RNU5B-1 Arina Puzriakova Tag gene-checked was removed from gene: RNU5B-1.
DDG2P v6.438 RNU5B-1 Arina Puzriakova Tag gene-checked was removed from gene: RNU5B-1.
Fetal anomalies v6.169 RNU5B-1 Arina Puzriakova Tag gene-checked was removed from gene: RNU5B-1.
Intellectual disability v9.330 RNU4-2 Arina Puzriakova Tag gene-checked was removed from gene: RNU4-2.
Severe microcephaly v8.34 RNU4-2 Arina Puzriakova Tag gene-checked was removed from gene: RNU4-2.
Fetal anomalies v6.169 RNU4-2 Arina Puzriakova Tag gene-checked was removed from gene: RNU4-2.
DDG2P v6.438 RNU4-2 Arina Puzriakova Tag gene-checked was removed from gene: RNU4-2.
Early onset or syndromic epilepsy v8.159 RNU4-2 Arina Puzriakova Tag gene-checked was removed from gene: RNU4-2.
DDG2P v6.438 RNU12 Arina Puzriakova Tag gene-checked was removed from gene: RNU12.
Rare syndromic craniosynostosis or isolated multisuture synostosis v6.4 RNU12 Arina Puzriakova Tag gene-checked was removed from gene: RNU12.
Fetal anomalies v6.169 RNU12 Arina Puzriakova Tag gene-checked was removed from gene: RNU12.
Rare genetic inflammatory skin disorders v4.18 RNU12 Arina Puzriakova Tag gene-checked was removed from gene: RNU12.
Monogenic short stature v1.31 RNPC3 Arina Puzriakova Tag gene-checked was removed from gene: RNPC3.
Intellectual disability v9.330 RNPC3 Arina Puzriakova Tag gene-checked was removed from gene: RNPC3.
DDG2P v6.438 RNPC3 Arina Puzriakova Tag gene-checked was removed from gene: RNPC3.
Pituitary hormone deficiency v4.4 RNPC3 Arina Puzriakova Tag gene-checked was removed from gene: RNPC3.
Mitochondrial disorders v9.46 PITRM1 Arina Puzriakova Tag gene-checked was removed from gene: PITRM1.
Intellectual disability v9.330 PITRM1 Arina Puzriakova Tag gene-checked was removed from gene: PITRM1.
Likely inborn error of metabolism v8.100 PITRM1 Arina Puzriakova Tag gene-checked was removed from gene: PITRM1.
Ataxia and cerebellar anomalies - narrow panel v8.72 PITRM1 Arina Puzriakova Tag gene-checked was removed from gene: PITRM1.
Fetal anomalies v6.169 FRYL Ida Ertmanska Tag gene-checked tag was added to gene: FRYL.
Intellectual disability v9.330 FRYL Ida Ertmanska Tag gene-checked tag was added to gene: FRYL.
DDG2P v6.438 FRYL Ida Ertmanska Tag gene-checked tag was added to gene: FRYL.
Intellectual disability v9.330 FICD Ida Ertmanska Tag gene-checked was removed from gene: FICD.
Childhood onset hereditary spastic paraplegia v8.39 FICD Ida Ertmanska Tag gene-checked was removed from gene: FICD.
Neonatal diabetes v5.19 FICD Ida Ertmanska Tag gene-checked was removed from gene: FICD.
Hereditary neuropathy or pain disorder v7.43 FICD Ida Ertmanska Tag gene-checked was removed from gene: FICD.
Neonatal diabetes v5.19 FICD Ida Ertmanska Tag gene-checked tag was added to gene: FICD.
Intellectual disability v9.330 FICD Ida Ertmanska Tag gene-checked tag was added to gene: FICD.
DDG2P v6.438 FEZF2 Ida Ertmanska Tag gene-checked tag was added to gene: FEZF2.
Intellectual disability v9.330 FEM1B Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotype updated 19 Mar 2026.
Intellectual disability v9.330 FEM1B Ida Ertmanska Phenotypes for gene: FEM1B were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to Neurodevelopmental disorder with behavioral, ear, and skeletal abnormalities, OMIM:621263; neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071
Intellectual disability v9.329 FEM1B Ida Ertmanska Tag gene-checked was removed from gene: FEM1B.
DDG2P v6.438 FEM1B Ida Ertmanska Tag gene-checked was removed from gene: FEM1B.
DDG2P v6.438 FEM1B Ida Ertmanska Added comment: Comment on phenotypes: OMIM phenotype updated 19 Mar 2026.
DDG2P v6.438 FEM1B Ida Ertmanska Phenotypes for gene: FEM1B were changed from FEM1B-related neurodevelopmental disorder with or without brain abnormalities to Neurodevelopmental disorder with behavioral, ear, and skeletal abnormalities, OMIM:613539; FEM1B-related neurodevelopmental disorder with or without brain abnormalities
Fetal anomalies v6.169 FAM177A1 Ida Ertmanska Tag gene-checked tag was added to gene: FAM177A1.
DDG2P v6.437 FAM177A1 Ida Ertmanska Tag gene-checked tag was added to gene: FAM177A1.
Rare multisystem ciliopathy disorders v1.180 FAM149B1 Ida Ertmanska Tag gene-checked tag was added to gene: FAM149B1.
Intellectual disability v9.329 EPB41L3 Ida Ertmanska Tag gene-checked tag was added to gene: EPB41L3.
White matter disorders and cerebral calcification - narrow panel v7.18 EPB41L3 Ida Ertmanska Tag gene-checked tag was added to gene: EPB41L3.
Early onset or syndromic epilepsy v8.159 EPB41L3 Ida Ertmanska Tag gene-checked tag was added to gene: EPB41L3.
DDG2P v6.437 EIF3B Ida Ertmanska Tag gene-checked tag was added to gene: EIF3B.
Paediatric disorders - additional genes v7.35 EIF3B Ida Ertmanska Tag gene-checked tag was added to gene: EIF3B.
Fetal anomalies v6.169 EIF3B Ida Ertmanska Tag gene-checked tag was added to gene: EIF3B.
Paediatric disorders - additional genes v7.35 EIF3A Ida Ertmanska Tag gene-checked tag was added to gene: EIF3A.
DDG2P v6.437 EIF3A Ida Ertmanska Tag gene-checked tag was added to gene: EIF3A.
DDG2P v6.437 DOT1L Ida Ertmanska Phenotypes for gene: DOT1L were changed from DOT1L-related neurodevelopmental disorder with intracranial anomalies to Nil-Deshwar neurodevelopmental syndrome, OMIM:621265
DDG2P v6.436 DOT1L Ida Ertmanska Tag gene-checked was removed from gene: DOT1L.
Intellectual disability v9.329 DDX39B Ida Ertmanska Tag gene-checked tag was added to gene: DDX39B.
Fetal anomalies v6.169 DDX17 Ida Ertmanska Tag gene-checked tag was added to gene: DDX17.
DDG2P v6.436 DDX17 Ida Ertmanska Tag gene-checked tag was added to gene: DDX17.
DDG2P v6.436 CSDE1 Ida Ertmanska Tag gene-checked tag was added to gene: CSDE1.
Fetal anomalies v6.169 CSDE1 Ida Ertmanska Tag gene-checked tag was added to gene: CSDE1.
Intellectual disability v9.329 CFAP47 Ida Ertmanska Tag gene-checked tag was added to gene: CFAP47.
Cystic kidney disease v8.8 CFAP47 Ida Ertmanska Tag gene-checked tag was added to gene: CFAP47.
Fetal anomalies v6.169 CEP76 Ida Ertmanska Tag gene-checked tag was added to gene: CEP76.
Intellectual disability v9.329 CELF4 Ida Ertmanska Tag gene-checked tag was added to gene: CELF4.
Early onset or syndromic epilepsy v8.159 CELF4 Ida Ertmanska Tag gene-checked tag was added to gene: CELF4.
DDG2P v6.436 CELF4 Ida Ertmanska Tag gene-checked tag was added to gene: CELF4.
Fetal anomalies v6.169 CCDC32 Ida Ertmanska Tag gene-checked tag was added to gene: CCDC32.
Fetal anomalies v6.169 CACHD1 Ida Ertmanska Tag gene-checked tag was added to gene: CACHD1.
Paediatric disorders - additional genes v7.35 CACHD1 Ida Ertmanska Tag gene-checked tag was added to gene: CACHD1.
Fetal anomalies v6.169 C14orf80 Ida Ertmanska Tag gene-checked tag was added to gene: C14orf80.
DDG2P v6.436 C14orf80 Ida Ertmanska Tag gene-checked tag was added to gene: C14orf80.
Intellectual disability v9.329 TAOK2 Arina Puzriakova Publications for gene: TAOK2 were set to 39737487
Intellectual disability v9.328 TAOK2 Arina Puzriakova Tag gene-checked tag was added to gene: TAOK2.
Mitochondrial disorders v9.46 SUPV3L1 Arina Puzriakova Tag gene-checked tag was added to gene: SUPV3L1.
Intellectual disability v9.328 SUPV3L1 Arina Puzriakova Tag gene-checked tag was added to gene: SUPV3L1.
Likely inborn error of metabolism v8.100 SUPV3L1 Arina Puzriakova Tag gene-checked tag was added to gene: SUPV3L1.
DDG2P v6.436 SREBF2 Arina Puzriakova Tag gene-checked tag was added to gene: SREBF2.
DDG2P v6.436 SP9 Arina Puzriakova Phenotypes for gene: SP9 were changed from MONDO:0100038; SP9-related neurodevelopmental disorder with or without epileptic encephalopathy to complex neurodevelopmental disorder, MONDO:0100038; SP9-related neurodevelopmental disorder with or without epileptic encephalopathy
DDG2P v6.435 SP9 Arina Puzriakova Tag gene-checked tag was added to gene: SP9.
Intellectual disability v9.328 SMARCA1 Arina Puzriakova Tag gene-checked tag was added to gene: SMARCA1.
DDG2P v6.435 SLC13A1 Arina Puzriakova Tag gene-checked tag was added to gene: SLC13A1.
Intellectual disability v9.328 BRSK1 Ida Ertmanska Tag gene-checked tag was added to gene: BRSK1.
Fetal anomalies v6.169 SIX2 Arina Puzriakova Publications for gene: SIX2 were set to
Fetal anomalies v6.168 SIX2 Arina Puzriakova Phenotypes for gene: SIX2 were changed from frontonasal dysplasia to six2-related frontonasal dysplasia, MONDO:0044628
Fetal anomalies v6.167 SIX2 Arina Puzriakova Tag gene-checked tag was added to gene: SIX2.
Early onset or syndromic epilepsy v8.159 BRSK1 Ida Ertmanska Tag gene-checked tag was added to gene: BRSK1.
Fetal anomalies v6.167 SHROOM4 Arina Puzriakova Tag gene-checked tag was added to gene: SHROOM4.
Fetal anomalies v6.167 BRF2 Ida Ertmanska Tag gene-checked tag was added to gene: BRF2.
DDG2P v6.435 ATXN7L3 Ida Ertmanska Tag gene-checked tag was added to gene: ATXN7L3.
Fetal anomalies v6.167 SHROOM4 Arina Puzriakova Phenotypes for gene: SHROOM4 were changed from Abnormal corpus callosum; congenital anomalies of the urinary tract and the anorectal, cardiovascular and central nervous systems; Stocco dos Santos X-linked mental retardation syndrome, 300434 to Abnormal corpus callosum; congenital anomalies of the urinary tract and the anorectal, cardiovascular and central nervous systems
Fetal anomalies v6.166 SHROOM4 Arina Puzriakova Publications for gene: SHROOM4 were set to 36379543; 32565546
DDG2P v6.435 SF1 Arina Puzriakova Tag gene-checked tag was added to gene: SF1.
Intellectual disability v9.328 SF1 Arina Puzriakova Tag gene-checked tag was added to gene: SF1.
DDG2P v6.435 SF1 Arina Puzriakova Phenotypes for gene: SF1 were changed from MONDO:0700092; SF1-related neurodevelopmental disorder to neurodevelopmental disorder, MONDO:0700092; SF1-related neurodevelopmental disorder
DDG2P v6.434 SEPHS1 Arina Puzriakova Phenotypes for gene: SEPHS1 were changed from MONDO:0700092; SEPHS1-related neurodevelopmental disorder to neurodevelopmental disorder, MONDO:0700092; SEPHS1-related neurodevelopmental disorder
Fetal anomalies v6.165 TMEM251 Ida Ertmanska commented on gene: TMEM251
DDG2P v6.433 SEPHS1 Arina Puzriakova Tag gene-checked tag was added to gene: SEPHS1.
Intellectual disability v9.328 SEPHS1 Arina Puzriakova Phenotypes for gene: SEPHS1 were changed from Neurodevelopmental disorder, MONDO:0700092 to Ververi-Brady syndrome 2, OMIM:621325; Neurodevelopmental disorder, MONDO:0700092
Fetal anomalies v6.165 RSG1 Ida Ertmanska commented on gene: RSG1
Arthrogryposis v9.31 MYLPF Ida Ertmanska commented on gene: MYLPF
Fetal anomalies v6.165 SART3 Arina Puzriakova Tag gene-checked tag was added to gene: SART3.
Fetal anomalies v6.165 MYLPF Ida Ertmanska commented on gene: MYLPF
Fetal anomalies v6.165 TTC26 Ida Ertmanska commented on gene: TTC26
DDG2P v6.433 RYBP Arina Puzriakova Tag gene-checked tag was added to gene: RYBP.
DDG2P v6.433 RYBP Arina Puzriakova Phenotypes for gene: RYBP were changed from RYBP-related neurodevelopmental disorder with congenital anomalies; MONDO:0100038 to RYBP-related neurodevelopmental disorder with congenital anomalies; complex neurodevelopmental disorder, MONDO:0100038
Fetal anomalies v6.165 RSG1 Arina Puzriakova Tag gene-checked tag was added to gene: RSG1.
Fetal anomalies v6.165 H3F3B Ida Ertmanska commented on gene: H3F3B
Fetal anomalies v6.165 RSG1 Arina Puzriakova Phenotypes for gene: RSG1 were changed from ciliopathy to ciliopathy, MONDO:0005308
Fetal anomalies v6.164 RSG1 Arina Puzriakova Publications for gene: RSG1 were set to
Intellectual disability v9.327 WARS Ida Ertmanska commented on gene: WARS
Severe microcephaly v8.34 WARS Ida Ertmanska commented on gene: WARS
Retinal disorders v8.99 AP5M1 Ida Ertmanska Tag gene-checked tag was added to gene: AP5M1.
Fetal anomalies v6.163 ARF3 Ida Ertmanska Tag gene-checked tag was added to gene: ARF3.
Intellectual disability v9.327 ABI2 Ida Ertmanska Tag gene-checked tag was added to gene: ABI2.
Intellectual disability v9.327 RREB1 Arina Puzriakova Tag gene-checked tag was added to gene: RREB1.
Early onset or syndromic epilepsy v8.159 ABI2 Ida Ertmanska Tag gene-checked tag was added to gene: ABI2.
Fetal anomalies v6.163 ABI2 Ida Ertmanska Tag gene-checked tag was added to gene: ABI2.
White matter disorders and cerebral calcification - narrow panel v7.18 ABI2 Ida Ertmanska Tag gene-checked tag was added to gene: ABI2.
Fetal anomalies v6.163 RNU7-1 Arina Puzriakova Tag gene-checked tag was added to gene: RNU7-1.
Retinal disorders v8.99 RNU6-9 Arina Puzriakova Tag gene-checked tag was added to gene: RNU6-9.
Retinal disorders v8.99 RNU6-8 Arina Puzriakova Tag gene-checked tag was added to gene: RNU6-8.
Retinal disorders v8.99 RNU6-2 Arina Puzriakova Tag gene-checked tag was added to gene: RNU6-2.
Retinal disorders v8.99 RNU6-1 Arina Puzriakova Tag gene-checked tag was added to gene: RNU6-1.
DDG2P v6.432 RNU5B-1 Arina Puzriakova Tag locus-type-rna-small-nuclear tag was added to gene: RNU5B-1.
DDG2P v6.432 RNU5B-1 Arina Puzriakova Tag gene-checked tag was added to gene: RNU5B-1.
Fetal anomalies v6.163 RNU5B-1 Arina Puzriakova Tag locus-type-rna-small-nuclear tag was added to gene: RNU5B-1.
DDG2P v6.432 RNU2-2P Arina Puzriakova Phenotypes for gene: RNU2-2P were changed from RNU2-2-related neurodevelopmental disorder with seizures and hyperventilation; MONDO:0100038 to RNU2-2-related neurodevelopmental disorder with seizures and hyperventilation; complex neurodevelopmental disorder, MONDO:0100038; Developmental and epileptic encephalopathy 119, OMIM:621304
Early onset or syndromic epilepsy v8.159 RNU2-2P Arina Puzriakova Phenotypes for gene: RNU2-2P were changed from neurodevelopmental disorder, MONDO:0700092; epilepsy, MONDO:0005027 to Developmental and epileptic encephalopathy 119, OMIM:621304
Intellectual disability v9.327 RNU2-2P Arina Puzriakova Phenotypes for gene: RNU2-2P were changed from neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071 to Developmental and epileptic encephalopathy 119, OMIM:621304
Fetal anomalies v6.163 RNU2-2P Arina Puzriakova Phenotypes for gene: RNU2-2P were changed from neurodevelopmental disorder to Developmental and epileptic encephalopathy 119, OMIM:621304
DDG2P v6.431 RFX4 Arina Puzriakova Tag gene-checked tag was added to gene: RFX4.
DDG2P v6.431 RFX4 Arina Puzriakova Phenotypes for gene: RFX4 were changed from MONDO:0100038; RFX4-related neurodevelopmental disorder with autism and other behavioural abnormalities to complex neurodevelopmental disorder, MONDO:0100038; RFX4-related neurodevelopmental disorder with autism and other behavioural abnormalities
DDG2P v6.430 RFX3 Arina Puzriakova Tag gene-checked tag was added to gene: RFX3.
DDG2P v6.430 RFX3 Arina Puzriakova Phenotypes for gene: RFX3 were changed from RFX3-related neurodevelopmental disorder with autism and other behavioural abnormalities; MONDO:0100038 to RFX3-related neurodevelopmental disorder with autism and other behavioural abnormalities; complex neurodevelopmental disorder, MONDO:0100038
Paediatric disorders - additional genes v7.35 RBFOX2 Arina Puzriakova Tag gene-checked tag was added to gene: RBFOX2.
Fetal anomalies v6.162 RBBP5 Arina Puzriakova Publications for gene: RBBP5 were set to
Fetal anomalies v6.161 RBBP5 Arina Puzriakova Phenotypes for gene: RBBP5 were changed from neurodevelopmental disorder to neurodevelopmental disorder, MONDO:0700092
Fetal anomalies v6.160 RBBP5 Arina Puzriakova Tag gene-checked tag was added to gene: RBBP5.
DDG2P v6.429 RAB5C Arina Puzriakova Tag gene-checked tag was added to gene: RAB5C.
Hereditary ataxia with onset in adulthood v8.30 RAB3A Arina Puzriakova Tag gene-checked tag was added to gene: RAB3A.
Ataxia and cerebellar anomalies - narrow panel v8.72 RAB3A Arina Puzriakova Tag gene-checked tag was added to gene: RAB3A.
Clefting v6.23 PRKCI Arina Puzriakova Tag gene-checked tag was added to gene: PRKCI.
Fetal anomalies v6.160 PRKCI Arina Puzriakova Tag gene-checked tag was added to gene: PRKCI.
Fetal anomalies v6.160 PRKCI Arina Puzriakova Phenotypes for gene: PRKCI were changed from Van der Woude syndrome to Van der Woude syndrome, MONDO:0019508
Intellectual disability v9.326 PPP1R21 Arina Puzriakova Tag gene-checked was removed from gene: PPP1R21.
DDG2P v6.429 PPP1R21 Arina Puzriakova Tag gene-checked was removed from gene: PPP1R21.
Fetal anomalies v6.159 TMEM251 Ida Ertmanska Tag new-gene-name tag was added to gene: TMEM251.
Fetal anomalies v6.159 PPP1R21 Arina Puzriakova Tag gene-checked was removed from gene: PPP1R21.
Fetal anomalies v6.159 PPP1R21 Arina Puzriakova Tag gene-checked tag was added to gene: PPP1R21.
Fetal anomalies v6.159 RSG1 Ida Ertmanska Tag new-gene-name tag was added to gene: RSG1.
Arthrogryposis v9.31 MYLPF Ida Ertmanska Tag new-gene-name tag was added to gene: MYLPF.
Fetal anomalies v6.159 MYLPF Ida Ertmanska Tag new-gene-name tag was added to gene: MYLPF.
Acute rhabdomyolysis v2.7 POC5 Arina Puzriakova Tag dd_review was removed from gene: POC5.
Tag gene-checked tag was added to gene: POC5.
Rare syndromic craniosynostosis or isolated multisuture synostosis v6.4 H3F3B Ida Ertmanska Tag new-gene-name tag was added to gene: H3F3B.
Monogenic diabetes v3.14 POC5 Arina Puzriakova Tag gene-checked tag was added to gene: POC5.
Lipodystrophy - childhood onset v4.67 POC5 Arina Puzriakova Tag gene-checked tag was added to gene: POC5.
Fetal anomalies v6.159 H3F3B Ida Ertmanska Tag new-gene-name tag was added to gene: H3F3B.
Ophthalmological ciliopathies v5.15 POC5 Arina Puzriakova Tag gene-checked tag was added to gene: POC5.
Retinal disorders v8.99 POC5 Arina Puzriakova Tag gene-checked tag was added to gene: POC5.
Rhabdomyolysis and metabolic muscle disorders v5.17 POC5 Arina Puzriakova Tag dd_review was removed from gene: POC5.
Tag gene-checked tag was added to gene: POC5.
Fetal anomalies v6.159 TTC26 Ida Ertmanska Tag new-gene-name tag was added to gene: TTC26.
Severe microcephaly v8.34 WARS Ida Ertmanska Tag new-gene-name tag was added to gene: WARS.
DDG2P v6.429 PLXNB2 Arina Puzriakova Tag gene-checked tag was added to gene: PLXNB2.
Intellectual disability v9.326 WARS Ida Ertmanska Tag new-gene-name tag was added to gene: WARS.
DDG2P v6.429 PHF5A Arina Puzriakova Phenotypes for gene: PHF5A were changed from PHF5A-related neurodevelopmental disorder with congenital malformations to PHF5A-related neurodevelopmental disorder with congenital malformations; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v9.326 PHF5A Arina Puzriakova Phenotypes for gene: PHF5A were changed from PHF5A-related neurodevelopmental disorder with congenital malformations to PHF5A-related neurodevelopmental disorder with congenital malformations; neurodevelopmental disorder, MONDO:0700092
Fetal anomalies v6.159 PHF5A Arina Puzriakova Phenotypes for gene: PHF5A were changed from PHF5A-related neurodevelopmental disorder with congenital malformations to PHF5A-related neurodevelopmental disorder with congenital malformations; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v9.325 PHF5A Arina Puzriakova Tag gene-checked tag was added to gene: PHF5A.
DDG2P v6.428 PHF12 Arina Puzriakova Tag gene-checked tag was added to gene: PHF12.
Intellectual disability v9.325 PHF12 Arina Puzriakova Tag gene-checked tag was added to gene: PHF12.
DDG2P v6.428 PHF12 Arina Puzriakova Phenotypes for gene: PHF12 were changed from MONDO:0700092; PHF12-related developmental disorder to neurodevelopmental disorder, MONDO:0700092; PHF12-related developmental disorder
Fetal anomalies v6.158 PDIA6 Arina Puzriakova Tag gene-checked tag was added to gene: PDIA6.
Thrombocythaemia v1.12 SH2B3 Ida Ertmanska commented on gene: SH2B3
Intellectual disability v9.325 TANC2 Eleanor Williams Phenotypes for gene: TANC2 were changed from Intellectual developmental disorder with autistic features and language delay, with or without seizures, 618906 to Intellectual developmental disorder with autistic features and language delay, with or without seizures, OMIM:618906; intellectual developmental disorder with autistic features and language delay, with or without seizures, MONDO:0030051
Early onset or syndromic epilepsy v8.158 TANC2 Eleanor Williams Phenotypes for gene: TANC2 were changed from Intellectual developmental disorder with autistic features and language delay, with or without seizures, OMIM:618906 to Intellectual developmental disorder with autistic features and language delay, with or without seizures, OMIM:618906; intellectual developmental disorder with autistic features and language delay, with or without seizures, MONDO:0030051
Fetal anomalies v6.158 ZNF865 Eleanor Williams Tag Q1_26_promote_green tag was added to gene: ZNF865.
Fetal anomalies v6.158 ZNF865 Eleanor Williams Classified gene: ZNF865 as Amber List (moderate evidence)
Fetal anomalies v6.158 ZNF865 Eleanor Williams Added comment: Comment on list classification: Promoting to amber with a recommendation of a green rating with a monoallelic MOI following GMS review.
Fetal anomalies v6.158 ZNF865 Eleanor Williams Gene: znf865 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v8.72 JAM2 Eleanor Williams Phenotypes for gene: JAM2 were changed from Basal ganglia calcification, idiopathic, 8, autosomal recessive, OMIM:618824 to Basal ganglia calcification, idiopathic, 8, autosomal recessive, OMIM:618824; basal ganglia calcification, idiopathic, 8, autosomal recessive, MONDO:0032938
White matter disorders and cerebral calcification - narrow panel v7.18 JAM2 Eleanor Williams Phenotypes for gene: JAM2 were changed from Basal ganglia calcification, idiopathic, 8, autosomal recessive, OMIM:618824 to Basal ganglia calcification, idiopathic, 8, autosomal recessive, OMIM:618824; basal ganglia calcification, idiopathic, 8, autosomal recessive, MONDO:0032938
Hereditary ataxia with onset in adulthood v8.30 JAM2 Eleanor Williams Phenotypes for gene: JAM2 were changed from Basal ganglia calcification, idiopathic, 8, autosomal recessive, OMIM:618824 to Basal ganglia calcification, idiopathic, 8, autosomal recessive, OMIM:618824; basal ganglia calcification, idiopathic, 8, autosomal recessive, MONDO:0032938
Intellectual disability v9.324 TYW1 Eleanor Williams Phenotypes for gene: TYW1 were changed from cerebral palsy, MONDO:0006497 to cerebral palsy, MONDO:0006497; intellectual disability, MONDO:0001071
DDG2P v6.427 SHOX Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: Although this gene is associated with X-linked MOI (allelic requirement) in Gene2Phenotype, it is on the pseudoautosomal region. Hence, the MOI should remain as 'BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal'.
DDG2P v6.427 SHOX Achchuthan Shanmugasundram Mode of inheritance for gene: SHOX 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 BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
DDG2P v6.426 SHOX Achchuthan Shanmugasundram Deleted their comment
DDG2P v6.426 SHOX Achchuthan Shanmugasundram edited their review of gene: SHOX: Added comment: Although this gene is associated with X-linked MOI in Gene2Phenotype, this gene is on the pseudoautosomal region. Hence, the MOI should be set as 'BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal'.; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Monogenic diabetes v3.14 ZNF808 Ida Ertmanska Phenotypes for gene: ZNF808 were changed from Diabetes to Pancreatic agenesis 3, OMIM:620991; diabetes mellitus, MONDO:0005015
Monogenic diabetes v3.13 ZNF808 Ida Ertmanska Publications for gene: ZNF808 were set to PMID: 41500078
Monogenic diabetes v3.12 ZNF808 Ida Ertmanska Classified gene: ZNF808 as Amber List (moderate evidence)
Monogenic diabetes v3.12 ZNF808 Ida Ertmanska Gene: znf808 has been classified as Amber List (Moderate Evidence).
Monogenic diabetes v3.11 ZNF808 Ida Ertmanska reviewed gene: ZNF808: Rating: GREEN; Mode of pathogenicity: None; Publications: 37973953, 41500078; Phenotypes: Pancreatic agenesis 3, OMIM:620991, diabetes mellitus, MONDO:0005015; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v9.323 GABRA3 Arina Puzriakova Publications for gene: GABRA3 were set to 41289009
Early onset or syndromic epilepsy v8.157 GABRA3 Arina Puzriakova Publications for gene: GABRA3 were set to 41289009
Monogenic diabetes v3.11 ZNF808 Ida Ertmanska Mode of inheritance for gene: ZNF808 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v9.322 CDC42BPB Arina Puzriakova Mode of inheritance for gene: CDC42BPB was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v8.156 CDC42BPB Arina Puzriakova Mode of inheritance for gene: CDC42BPB was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v9.321 CDC42BPB Arina Puzriakova Publications for gene: CDC42BPB were set to 32031333
Early onset or syndromic epilepsy v8.155 CDC42BPB Arina Puzriakova Phenotypes for gene: CDC42BPB were changed from Chilton-Okur-Chung neurodevelopmental syndrome, OMIM:619841 Chilton-Okur-Chung neurodevelopmental syndrome, MONDO:0859239 to Chilton-Okur-Chung neurodevelopmental syndrome, OMIM:619841; Chilton-Okur-Chung neurodevelopmental syndrome, MONDO:0859239
Intellectual disability v9.320 CDC42BPB Arina Puzriakova Tag Q1_26_promote_green tag was added to gene: CDC42BPB.
Early onset or syndromic epilepsy v8.154 CDC42BPB Arina Puzriakova Mode of inheritance for gene: CDC42BPB was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v9.320 KCNT2 Arina Puzriakova Publications for gene: KCNT2 were set to 29069600; 29740868
Intellectual disability v9.319 KCNT2 Arina Puzriakova Phenotypes for gene: KCNT2 were changed from Developmental and epileptic encephalopathy 57, OMIM:617771 developmental and epileptic encephalopathy, 57, MONDO:0033366 to Developmental and epileptic encephalopathy 57, OMIM:617771; developmental and epileptic encephalopathy, 57, MONDO:0033366
Ataxia and cerebellar anomalies - narrow panel v8.71 TRMT5 Ida Ertmanska gene: TRMT5 was added
gene: TRMT5 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Mode of inheritance for gene: TRMT5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRMT5 were set to 35342985
Phenotypes for gene: TRMT5 were set to Peripheral neuropathy with variable spasticity, exercise intolerance, and developmental delay, OMIM:616539
Review for gene: TRMT5 was set to RED
Added comment: PMID: 35342985 Argente-Escrig et al., 2022
3 cases from apparently unrelated Southern European families with infantile onset demyelinating neuropathy. All compound het for the same TRMT5 variants: [c.312_315del; p.Ile105Serfs*4] and [c.665 T > C; p.Ile222Thr].
The cerebellar ataxia was described as mild (gait disturbance). Neuropathy is the main presentation.
Sources: Literature
Adult onset hereditary spastic paraplegia v6.9 TRMT5 Ida Ertmanska Classified gene: TRMT5 as Amber List (moderate evidence)
Adult onset hereditary spastic paraplegia v6.9 TRMT5 Ida Ertmanska Added comment: Comment on list classification: There are at least 2 unrelated families with affected individuals harbouring biallelic TRMT5 variants, presenting with spastic paraparesis / spastic gait. However, spasticity is not the main presenting feature of this progressive syndrome. Based on available evidence, this gene can only be rated Amber for Adult onset hereditary spastic paraplegia.
Adult onset hereditary spastic paraplegia v6.9 TRMT5 Ida Ertmanska Gene: trmt5 has been classified as Amber List (Moderate Evidence).
Adult onset hereditary spastic paraplegia v6.8 TRMT5 Ida Ertmanska gene: TRMT5 was added
gene: TRMT5 was added to Adult onset hereditary spastic paraplegia. Sources: Literature
Mode of inheritance for gene: TRMT5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRMT5 were set to 26189817; 29021354
Phenotypes for gene: TRMT5 were set to Peripheral neuropathy with variable spasticity, exercise intolerance, and developmental delay, OMIM:616539
Review for gene: TRMT5 was set to AMBER
Added comment: PMID: 26189817 Powell et al., 2015
Subject 73901- lifelong exercise intolerance, presented at the age of 25 years with prolonged dyspnea associated with lactic acidosis, diagnosed with a mitochondrial myopathy associated with a marked histochemical and biochemical deficiency of COX and a defect in complex III activity. At 35 yrs showed hyperreflexia and extensor plantar reflexes with some clinical spasticity. Compound het for c.312_315del (p.Ile105Serfs∗4) frameshift and a c.872G>A (p.Arg291His).

PMID: 29021354 Tarnopolsky et al., 2017
P1 - 46yo female, presented at age 27 years with a lifelong history of exercise intolerance, muscle weakness, and shortness of breath on exertion. EMG normal at 27yo, progressive axonal sensory neuropathy seen at 43 years. 46yo - progression of proximal weakness with a waddling and spastic gait.
P2 (sister of P1) - presented at age 33 yrs with worsening gait and an increased frequency of falls; diagnosed with cerebral palsy in childhood; lower extremities: mild proximal and severe distal weakness/atrophy, severe spasticity, and upgoing toes; she showed gross motor, cognitive, and speech delays.
Both sisters compound het for TRMT5: c.872G>A (p.Arg291His) and c.312_315del (p.Ile105Serfs4X), confirmed in trans.

TRMT5 is associated with Peripheral neuropathy with variable spasticity, exercise intolerance, and developmental delay, OMIM:616539 in OMIM (accessed 18 Mar 2026).
Sources: Literature
Intellectual disability v9.318 ISCA-37448-Loss Ida Ertmanska Variant type for ISCA-37448-Loss was changed from small to cnv_loss.
Early onset or syndromic epilepsy v8.153 ISCA-37448-Loss Ida Ertmanska Variant type for ISCA-37448-Loss was changed from small to cnv_loss.
Early onset or syndromic epilepsy v8.152 AMACR Ida Ertmanska changed review comment from: Comment on list classification: More than 50% of patients with biallelic AMACR variants present with seizures or have an epilepsy diagnosis. Based on available evidence, AMACR is tagged for promotion to Green on Early onset or syndromic epilepsy at the next update. As the seizures may be caused by pathological brain lesions, the gene is also tagged for expert review, to ascertain whether this gene is in scope of testing.; to: Comment on list classification: More than 50% of patients with biallelic AMACR variants present with seizures / have an epilepsy diagnosis. Based on available evidence, AMACR is tagged for promotion to Green on Early onset or syndromic epilepsy at the next update. As the seizures may be caused by pathological brain lesions, the gene is also tagged for expert review, to ascertain whether this gene is in scope of testing.
Early onset or syndromic epilepsy v8.152 AMACR Ida Ertmanska Tag Q1_26_expert_review tag was added to gene: AMACR.
Early onset or syndromic epilepsy v8.152 AMACR Ida Ertmanska edited their review of gene: AMACR: Added comment: Comment on list classification: More than 50% of patients with biallelic AMACR variants present with seizures or have an epilepsy diagnosis. Based on available evidence, AMACR is tagged for promotion to Green on Early onset or syndromic epilepsy at the next update. As the seizures may be caused by pathological brain lesions, the gene is also tagged for expert review, to ascertain whether this gene is in scope of testing.; Changed rating: GREEN
Early onset or syndromic epilepsy v8.152 AMACR Ida Ertmanska Tag Q1_26_promote_green tag was added to gene: AMACR.
Early onset or syndromic epilepsy v8.152 AMACR Ida Ertmanska Classified gene: AMACR as Amber List (moderate evidence)
Early onset or syndromic epilepsy v8.152 AMACR Ida Ertmanska Gene: amacr has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v8.151 AMACR Ida Ertmanska gene: AMACR was added
gene: AMACR was added to Early onset or syndromic epilepsy. Sources: Literature
Mode of inheritance for gene: AMACR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AMACR were set to 37452652
Phenotypes for gene: AMACR were set to Alpha-methylacyl-CoA racemase deficiency, OMIM:614307
Review for gene: AMACR was set to AMBER
Added comment: PMID: 37452652 Palacio-Montoya et al., 2023
3 sibs with recurrent episodes of encephalopathy, seizures, and behavioural disturbances. In all 3, brain MRI showed lesions in the thalami, cerebral peduncles, and mesencephalic tegmentum, as well as brain volume loss. Homozygous AMACR c826 G>C p.Ala276Pro variant detected in affected individuals.

In a literature review in the same paper, 9/16 previously reported patients with AMACR deficency had seizures / epilepsy, which correlated with abnormal brain MRI findings. The most common variant was c.154T>C, p.Ser52Pro (7/16 patients).
Sources: Literature
COVID-19 research v1.147 ISCA-37433-Loss Arina Puzriakova Classified Region: ISCA-37433-Loss as No list
COVID-19 research v1.147 ISCA-37433-Loss Arina Puzriakova Added comment: Comment on list classification: This region has been deprecated by ClinGen and therefore has been removed from the panel.

This region has also been removed from all GMS panels following NHS Genomic Medicine Service approval.
COVID-19 research v1.147 ISCA-37433-Loss Arina Puzriakova Region: isca-37433-loss has been removed from the panel.
Intellectual disability v9.317 ISCA-37433-Loss Arina Puzriakova Classified Region: ISCA-37433-Loss as No list
Intellectual disability v9.317 ISCA-37433-Loss Arina Puzriakova Region: isca-37433-loss has been removed from the panel.
COVID-19 research v1.146 ISCA-37433-Loss Arina Puzriakova Tag curated_removed tag was added to Region: ISCA-37433-Loss.
Early onset or syndromic epilepsy v8.150 ISCA-37433-Loss Arina Puzriakova Classified Region: ISCA-37433-Loss as No list
Early onset or syndromic epilepsy v8.150 ISCA-37433-Loss Arina Puzriakova Region: isca-37433-loss has been removed from the panel.
Clefting v6.23 ISCA-37433-Loss Arina Puzriakova Classified Region: ISCA-37433-Loss as No list
Clefting v6.23 ISCA-37433-Loss Arina Puzriakova Region: isca-37433-loss has been removed from the panel.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.85 ISCA-37433-Loss Arina Puzriakova Classified Region: ISCA-37433-Loss as No list
Primary immunodeficiency or monogenic inflammatory bowel disease v8.85 ISCA-37433-Loss Arina Puzriakova Region: isca-37433-loss has been removed from the panel.
Intellectual disability v9.316 ISCA-37433-Loss Arina Puzriakova Tag Q3_25_demote_red was removed from Region: ISCA-37433-Loss.
Tag curated_removed tag was added to Region: ISCA-37433-Loss.
Early onset or syndromic epilepsy v8.149 ISCA-37433-Loss Arina Puzriakova Tag Q3_25_demote_red was removed from Region: ISCA-37433-Loss.
Tag curated_removed tag was added to Region: ISCA-37433-Loss.
Clefting v6.22 ISCA-37433-Loss Arina Puzriakova Tag Q3_25_demote_red was removed from Region: ISCA-37433-Loss.
Tag curated_removed tag was added to Region: ISCA-37433-Loss.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.84 ISCA-37433-Loss Arina Puzriakova Tag Q3_25_demote_red was removed from Region: ISCA-37433-Loss.
Tag curated_removed tag was added to Region: ISCA-37433-Loss.
Intellectual disability v9.316 ISCA-37433-Loss Arina Puzriakova commented on Region: ISCA-37433-Loss: The rating of this gene has been updated to Grey (removed) following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v8.149 ISCA-37433-Loss Arina Puzriakova commented on Region: ISCA-37433-Loss: The rating of this gene has been updated to Grey (removed) following NHS Genomic Medicine Service approval.
Clefting v6.22 ISCA-37433-Loss Arina Puzriakova commented on Region: ISCA-37433-Loss: The rating of this gene has been updated to Grey (removed) following NHS Genomic Medicine Service approval.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.84 ISCA-37433-Loss Arina Puzriakova commented on Region: ISCA-37433-Loss: The rating of this gene has been updated to Grey (removed) following NHS Genomic Medicine Service approval.
Intellectual disability v9.316 ISCA-37433-Gain Arina Puzriakova Classified Region: ISCA-37433-Gain as No list
Intellectual disability v9.316 ISCA-37433-Gain Arina Puzriakova Region: isca-37433-gain has been removed from the panel.
Intellectual disability v9.315 ISCA-37433-Gain Arina Puzriakova Tag Q3_25_demote_red was removed from Region: ISCA-37433-Gain.
Tag curated_removed tag was added to Region: ISCA-37433-Gain.
Intellectual disability v9.315 ISCA-37433-Gain Arina Puzriakova commented on Region: ISCA-37433-Gain: The rating of this gene has been updated to Grey (removed) following NHS Genomic Medicine Service approval.
Ataxia and cerebellar anomalies - narrow panel v8.70 ISCA-37404-Loss Arina Puzriakova Tag curated_removed tag was added to Region: ISCA-37404-Loss.
Paediatric motor neuronopathies v3.13 ISCA-37404-Loss Arina Puzriakova Tag curated_removed tag was added to Region: ISCA-37404-Loss.
Early onset or syndromic epilepsy v8.149 ISCA-37404-Loss Arina Puzriakova Tag curated_removed tag was added to Region: ISCA-37404-Loss.
Intellectual disability v9.315 ISCA-37404-Loss Arina Puzriakova Tag curated_removed tag was added to Region: ISCA-37404-Loss.
Hereditary ataxia with onset in adulthood v8.29 ISCA-37404-Loss Arina Puzriakova Tag curated_removed tag was added to Region: ISCA-37404-Loss.
Intellectual disability v9.315 ISCA-37404-Loss Arina Puzriakova Classified Region: ISCA-37404-Loss as No list
Intellectual disability v9.315 ISCA-37404-Loss Arina Puzriakova Region: isca-37404-loss has been removed from the panel.
Hereditary ataxia with onset in adulthood v8.29 ISCA-37404-Loss Arina Puzriakova Classified Region: ISCA-37404-Loss as No list
Hereditary ataxia with onset in adulthood v8.29 ISCA-37404-Loss Arina Puzriakova Region: isca-37404-loss has been removed from the panel.
Hereditary ataxia with onset in adulthood v8.28 ISCA-37404-Loss Arina Puzriakova Tag Q3_25_demote_red was removed from Region: ISCA-37404-Loss.
Hereditary ataxia with onset in adulthood v8.28 ISCA-37404-Loss Arina Puzriakova commented on Region: ISCA-37404-Loss: The rating of this gene has been updated to Grey (removed) following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v8.149 ISCA-37404-Loss Arina Puzriakova Classified Region: ISCA-37404-Loss as No list
Early onset or syndromic epilepsy v8.149 ISCA-37404-Loss Arina Puzriakova Region: isca-37404-loss has been removed from the panel.
Intellectual disability v9.314 ISCA-37404-Loss Arina Puzriakova Tag Q3_25_demote_red was removed from Region: ISCA-37404-Loss.
Intellectual disability v9.314 ISCA-37404-Loss Arina Puzriakova commented on Region: ISCA-37404-Loss: The rating of this gene has been updated to Grey (removed) following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v8.148 ISCA-37404-Loss Arina Puzriakova Tag Q3_25_demote_red was removed from Region: ISCA-37404-Loss.
Early onset or syndromic epilepsy v8.148 ISCA-37404-Loss Arina Puzriakova commented on Region: ISCA-37404-Loss: The rating of this gene has been updated to Grey (removed) following NHS Genomic Medicine Service approval.
Paediatric motor neuronopathies v3.13 ISCA-37404-Loss Arina Puzriakova Classified Region: ISCA-37404-Loss as No list
Paediatric motor neuronopathies v3.13 ISCA-37404-Loss Arina Puzriakova Region: isca-37404-loss has been removed from the panel.
Paediatric motor neuronopathies v3.12 ISCA-37404-Loss Arina Puzriakova Tag Q3_25_demote_red was removed from Region: ISCA-37404-Loss.
Paediatric motor neuronopathies v3.12 ISCA-37404-Loss Arina Puzriakova commented on Region: ISCA-37404-Loss: The rating of this gene has been updated to Grey (removed) following NHS Genomic Medicine Service approval.
Ataxia and cerebellar anomalies - narrow panel v8.70 ISCA-37404-Loss Arina Puzriakova Classified Region: ISCA-37404-Loss as No list
Ataxia and cerebellar anomalies - narrow panel v8.70 ISCA-37404-Loss Arina Puzriakova Region: isca-37404-loss has been removed from the panel.
Ataxia and cerebellar anomalies - narrow panel v8.69 ISCA-37404-Loss Arina Puzriakova Tag Q3_25_demote_red was removed from Region: ISCA-37404-Loss.
Ataxia and cerebellar anomalies - narrow panel v8.69 ISCA-37404-Loss Arina Puzriakova commented on Region: ISCA-37404-Loss: The rating of this gene has been updated to Grey (removed) following NHS Genomic Medicine Service approval.
Intellectual disability v9.314 ISCA-37404-Gain Arina Puzriakova Classified Region: ISCA-37404-Gain as No list
Intellectual disability v9.314 ISCA-37404-Gain Arina Puzriakova Region: isca-37404-gain has been removed from the panel.
Intellectual disability v9.313 ISCA-37404-Gain Arina Puzriakova Tag curated_removed tag was added to Region: ISCA-37404-Gain.
Intellectual disability v9.313 ISCA-37404-Gain Arina Puzriakova Tag Q3_25_demote_red was removed from Region: ISCA-37404-Gain.
Intellectual disability v9.313 ISCA-37404-Gain Arina Puzriakova commented on Region: ISCA-37404-Gain: The rating of this gene has been updated to Grey (removed) following NHS Genomic Medicine Service approval.
Intellectual disability v9.313 ISCA-37448-Loss Arina Puzriakova Classified Region: ISCA-37448-Loss as Green List (high evidence)
Intellectual disability v9.313 ISCA-37448-Loss Arina Puzriakova Region: isca-37448-loss has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v8.148 ISCA-37448-Loss Arina Puzriakova Classified Region: ISCA-37448-Loss as Green List (high evidence)
Early onset or syndromic epilepsy v8.148 ISCA-37448-Loss Arina Puzriakova Region: isca-37448-loss has been classified as Green List (High Evidence).
Intellectual disability v9.312 ISCA-37448-Loss Arina Puzriakova Tag Q3_25_promote_green was removed from Region: ISCA-37448-Loss.
Early onset or syndromic epilepsy v8.147 ISCA-37448-Loss Arina Puzriakova Tag Q3_25_promote_green was removed from Region: ISCA-37448-Loss.
Intellectual disability v9.312 ISCA-37448-Loss Arina Puzriakova commented on Region: ISCA-37448-Loss: The rating of this region has been updated to Green following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v8.147 ISCA-37448-Loss Arina Puzriakova commented on Region: ISCA-37448-Loss: The rating of this region has been updated to Green following NHS Genomic Medicine Service approval.
Malformations of cortical development v7.39 ISCA-46300-Loss Arina Puzriakova Classified Region: ISCA-46300-Loss as Green List (high evidence)
Malformations of cortical development v7.39 ISCA-46300-Loss Arina Puzriakova Region: isca-46300-loss has been classified as Green List (High Evidence).
Intellectual disability v9.312 ISCA-46300-Loss Arina Puzriakova Classified Region: ISCA-46300-Loss as Green List (high evidence)
Intellectual disability v9.312 ISCA-46300-Loss Arina Puzriakova Region: isca-46300-loss has been classified as Green List (High Evidence).
Malformations of cortical development v7.38 ISCA-46300-Loss Arina Puzriakova Tag Q3_25_promote_green was removed from Region: ISCA-46300-Loss.
Intellectual disability v9.311 ISCA-46300-Loss Arina Puzriakova Tag Q3_25_promote_green was removed from Region: ISCA-46300-Loss.
Malformations of cortical development v7.38 ISCA-46300-Loss Arina Puzriakova commented on Region: ISCA-46300-Loss: The rating of this region has been updated to Green following NHS Genomic Medicine Service approval.
Intellectual disability v9.311 ISCA-46300-Loss Arina Puzriakova commented on Region: ISCA-46300-Loss: The rating of this region has been updated to Green following NHS Genomic Medicine Service approval.
Severe microcephaly v8.34 ISCA-46300-Loss Arina Puzriakova changed review comment from: Comment on list classification: This region has Sufficient Evidence for Haploinsufficiency in ClinGen, however, microcephaly reported in patients is often now within the severity range relevant to this panel (OFC reported in 27399968; 22180641: 10-15th, 0.6-2nd, 3rd, 10th percentile) so will include as Amber based on this evidence.; to: Comment on list classification: This region has Sufficient Evidence for Haploinsufficiency in ClinGen, however, microcephaly reported in patients is often not within the severity range relevant to this panel (OFC reported in 27399968; 22180641: 10-15th, 0.6-2nd, 3rd, 10th percentile) so classifying as Amber based on this evidence.
Intellectual disability v9.311 ISCA-46296-Loss Arina Puzriakova Classified Region: ISCA-46296-Loss as Green List (high evidence)
Intellectual disability v9.311 ISCA-46296-Loss Arina Puzriakova Region: isca-46296-loss has been classified as Green List (High Evidence).
Intellectual disability v9.310 ISCA-46296-Loss Arina Puzriakova Tag Q3_25_promote_green was removed from Region: ISCA-46296-Loss.
Intellectual disability v9.310 ISCA-46296-Loss Arina Puzriakova commented on Region: ISCA-46296-Loss: The rating of this region has been updated to Green following NHS Genomic Medicine Service approval.
Intellectual disability v9.310 ISCA-37498-Loss Arina Puzriakova Classified Region: ISCA-37498-Loss as Green List (high evidence)
Intellectual disability v9.310 ISCA-37498-Loss Arina Puzriakova Region: isca-37498-loss has been classified as Green List (High Evidence).
Intellectual disability v9.309 ISCA-37498-Loss Arina Puzriakova Tag Q3_25_promote_green was removed from Region: ISCA-37498-Loss.
Adult onset neurodegenerative disorder v8.19 ISCA-37446-Loss Arina Puzriakova Deleted their comment
Intellectual disability v9.309 ISCA-37498-Loss Arina Puzriakova commented on Region: ISCA-37498-Loss: The rating of this region has been updated to Green following NHS Genomic Medicine Service approval.
Adult onset neurodegenerative disorder v8.19 ISCA-37446-Loss Arina Puzriakova commented on Region: ISCA-37446-Loss: The rating of this region has been updated to Green following NHS Genomic Medicine Service approval.
Adult onset neurodegenerative disorder v8.19 ISCA-37446-Loss Arina Puzriakova changed review comment from: The rating of this region has been updated to Green following NHS Genomic Medicine Service approval.; to: The rating of this region has been updated to Green following NHS Genomic Medicine Service approval. Additional information: regions can be added to the panel as this clinical indication has now moved to WGS testing. Other regions that were previously removed should also be reviewed.
Adult onset neurodegenerative disorder v8.19 ISCA-37446-Loss Arina Puzriakova Classified Region: ISCA-37446-Loss as Green List (high evidence)
Adult onset neurodegenerative disorder v8.19 ISCA-37446-Loss Arina Puzriakova Region: isca-37446-loss has been classified as Green List (High Evidence).
Adult onset neurodegenerative disorder v8.18 ISCA-37446-Loss Arina Puzriakova Tag Q3_25_promote_green was removed from Region: ISCA-37446-Loss.
Tag Q3_25_expert_review was removed from Region: ISCA-37446-Loss.
Tag Q3_25_NHS_review was removed from Region: ISCA-37446-Loss.
Adult onset neurodegenerative disorder v8.18 ISCA-37446-Loss Arina Puzriakova commented on Region: ISCA-37446-Loss: The rating of this region has been updated to Green following NHS Genomic Medicine Service approval.
Likely inborn error of metabolism v8.100 PEX14 Ida Ertmanska commented on gene: PEX14: Comment on mode of inheritance: There are 2 individuals reported with de novo heterozygous PEX14 variants and a mild peroxisome biogenesis disorder. The MOI should remain set to BIALLELIC, until more evidence emerges in support of dominant disease - added watchlist_moi tag.
Likely inborn error of metabolism v8.100 PEX14 Ida Ertmanska Phenotypes for gene: PEX14 were changed from Disorders of peroxisome biogenesis; Peroxisome biogenesis disorder 13A (Zellweger) to Peroxisome biogenesis disorder 13A (Zellweger), OMIM:614887; peroxisome biogenesis disorder 13A (Zellweger), MONDO:0013952
Likely inborn error of metabolism v8.99 PEX14 Ida Ertmanska Publications for gene: PEX14 were set to 27604308
Likely inborn error of metabolism v8.98 PEX14 Ida Ertmanska Tag watchlist_moi tag was added to gene: PEX14.
Likely inborn error of metabolism v8.98 PEX14 Ida Ertmanska reviewed gene: PEX14: Rating: GREEN; Mode of pathogenicity: None; Publications: 37493040; Phenotypes: Peroxisome biogenesis disorder 13A (Zellweger), OMIM:614887; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v9.309 WDR83 Ida Ertmanska edited their review of gene: WDR83: Changed publications to: 19726548, 28332277, 37509073, 41381792
Intellectual disability v9.309 WDR83 Ida Ertmanska changed review comment from: PMID: 41381792 Tabata et al., 2025
7yo Japanese female patient presenting with global developmental delay, intellectual disability, microcephaly, and dysmorphic features. Brain MRI at 7 months showed enlarged bilateral ventricles. WES detected a de novo heterozygous WDR83 variant [NM_001099737; c.653 T > C,p.(L218P)].

Functional: Overexpression of WDR83-L218P in mice via in utero electroporation led to reduced proliferation of neural stem cells. Suggested GOF mechanism of disease.

PMID: 28332277 Kim et al., 2017
ADHD proband with de novo heterozygous WDR83 p.Gly127Arg variant (MAF = 0.000002542 in gnomAD v4)

PMID: 37509073 Wulf et al., 2023 - Homozygous Wdr83 knockout (KO) mice die around embryonic day 11 due to severe defects in cell proliferation and massive apoptosis.
PMID: 19726548 Hammerschmidt, Loeffler & Wolf, 2009 - Heterozygous Wdr83+/- mice display a normal phenotype, with no apparent abnormalities in brain structure or cerebral vascular architecture
Sources: Literature; to: PMID: 41381792 Tabata et al., 2025
7yo Japanese female patient presenting with global developmental delay, intellectual disability, microcephaly, and dysmorphic features. Brain MRI at 7 months showed enlarged bilateral ventricles. WES detected a de novo heterozygous WDR83 variant [NM_001099737; c.653 T > C,p.(L218P)].

Functional: Overexpression of WDR83-L218P in mice via in utero electroporation led to reduced proliferation of neural stem cells. Suggested GOF mechanism of disease.

PMID: 28332277 Kim et al., 2017
ADHD proband with de novo heterozygous WDR83 p.Gly127Arg variant (MAF = 0.000002542 in gnomAD v4)

PMID: 37509073 Wulf et al., 2023 - Homozygous Wdr83 knockout (KO) mice die around embryonic day 11 due to severe defects in cell proliferation and massive apoptosis.
PMID: 19726548 Hammerschmidt, Loeffler & Wolf, 2009 - Heterozygous Wdr83+/- mice display a normal phenotype, with no apparent abnormalities in brain structure or cerebral vascular architecture

WDR83 is not yet associated with disease in OMIM, ClinGen, or G2P (accessed 17 Mar 2026).
Sources: Literature
Intellectual disability v9.309 WDR83 Ida Ertmanska changed review comment from: Comment on list classification: There is 1 patient reported with GDD/ID, and 1 with ADHD - both individuals had heterozygous de novo variants in WDR83. There is some limited functional evidence in mice supporting WDR83 missense variants as causal in proliferation of neural stem cells. Based on available evidence, this gene can only be rated Amber at this time.; to: Comment on list classification: There is 1 patient reported with GDD/ID, and 1 with ADHD - both individuals had heterozygous de novo missense variants in WDR83. There is some limited functional evidence in mice supporting WDR83 missense variants as causal in proliferation of neural stem cells. Based on available evidence, this gene can only be rated Amber at this time.
Intellectual disability v9.309 WDR83 Ida Ertmanska Publications for gene: WDR83 were set to 28332277; 41381792
Intellectual disability v9.308 WDR83 Ida Ertmanska changed review comment from: Comment on list classification: There is 1 patient reported with GDD/ID and 1 with ADHD - both individuals had heterozygous de novo variants in WDR83. There is some limited functional evidence in mice supporting WDR83 missense variants as causal in proliferation of neural stem cells. Based on available evidence, this gene can only be rated Amber at this time.; to: Comment on list classification: There is 1 patient reported with GDD/ID, and 1 with ADHD - both individuals had heterozygous de novo variants in WDR83. There is some limited functional evidence in mice supporting WDR83 missense variants as causal in proliferation of neural stem cells. Based on available evidence, this gene can only be rated Amber at this time.
Intellectual disability v9.308 WDR83 Ida Ertmanska Classified gene: WDR83 as Amber List (moderate evidence)
Intellectual disability v9.308 WDR83 Ida Ertmanska Added comment: Comment on list classification: There is 1 patient reported with GDD/ID and 1 with ADHD - both individuals had heterozygous de novo variants in WDR83. There is some limited functional evidence in mice supporting WDR83 missense variants as causal in proliferation of neural stem cells. Based on available evidence, this gene can only be rated Amber at this time.
Intellectual disability v9.308 WDR83 Ida Ertmanska Gene: wdr83 has been classified as Amber List (Moderate Evidence).
Intellectual disability v9.307 WDR83 Ida Ertmanska gene: WDR83 was added
gene: WDR83 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: WDR83 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WDR83 were set to 28332277; 41381792
Phenotypes for gene: WDR83 were set to neurodevelopmental disorder, MONDO:0700092
Review for gene: WDR83 was set to AMBER
Added comment: PMID: 41381792 Tabata et al., 2025
7yo Japanese female patient presenting with global developmental delay, intellectual disability, microcephaly, and dysmorphic features. Brain MRI at 7 months showed enlarged bilateral ventricles. WES detected a de novo heterozygous WDR83 variant [NM_001099737; c.653 T > C,p.(L218P)].

Functional: Overexpression of WDR83-L218P in mice via in utero electroporation led to reduced proliferation of neural stem cells. Suggested GOF mechanism of disease.

PMID: 28332277 Kim et al., 2017
ADHD proband with de novo heterozygous WDR83 p.Gly127Arg variant (MAF = 0.000002542 in gnomAD v4)

PMID: 37509073 Wulf et al., 2023 - Homozygous Wdr83 knockout (KO) mice die around embryonic day 11 due to severe defects in cell proliferation and massive apoptosis.
PMID: 19726548 Hammerschmidt, Loeffler & Wolf, 2009 - Heterozygous Wdr83+/- mice display a normal phenotype, with no apparent abnormalities in brain structure or cerebral vascular architecture
Sources: Literature
Childhood onset hereditary spastic paraplegia v8.39 TYW1 Ida Ertmanska changed review comment from: PMID: 34077496 Li et al., 2021
2 Chinese sibs (non-consanguineous parents) reported with comp het TYW1 variants: NM_018264: c.616C>T, p.R206C & c.1166G>A, p. R389Q.
Proband CP_012_1, male - Wechsler Preschool and Primary Scale of Intelligence IQ = 40 at 7 years old (moderate ID);
CP_012_2, older sister - diagnosed with mixed type cerebral palsy (spasticity, dyskinesia), IQ <50 (moderate ID).
Parents confirmed heterozygous for 1 variant each. TYW1:c.616C>T - MAF in gnomADv4 = 0.0004900, including 1 homozygote. TYW1:c.1166G>A MAF in gnomAD v4 = 0.0001559, no homozygotes.

Functional evidence: TYW1 protein levels dramatically reduced in proband compared to controls; tyw1 deficiency in zebrafish resulted in ectopic neuronal cell migration in the brain and undifferentiated motor neuronal cells in the spinal cord - this was rescued by WT human and zebrafish tyw1 mRNA, but not by mRNA with patients' mutations. In addition, tyw1 knockdown zebrafish showed recuded swimming capacity. Kncokout tyw1-/- mice showed impaired motor function and reduced cognition in behavioural tests.

PMID: 38706838 Sun et al., 2024
Fucntional evidence: Study used brain organoid model and human embryonic stem cells to show that translation efficiency of UUU codon was compromised in TYW1−/− cells. Also, neuron differentiation was impaired when TYW1 was depleted.
Sources: Literature; to: PMID: 34077496 Li et al., 2021
2 Chinese sibs (non-consanguineous parents) reported with comp het TYW1 variants: NM_018264: c.616C>T, p.R206C & c.1166G>A, p. R389Q.
Proband CP_012_1, male - Wechsler Preschool and Primary Scale of Intelligence IQ = 40 at 7 years old (moderate ID);
CP_012_2, older sister - diagnosed with mixed type cerebral palsy (spasticity, dyskinesia), IQ <50 (moderate ID).
Parents confirmed heterozygous for 1 variant each. TYW1:c.616C>T - MAF in gnomADv4 = 0.0004900, including 1 homozygote. TYW1:c.1166G>A MAF in gnomAD v4 = 0.0001559, no homozygotes.

Functional evidence: TYW1 protein levels dramatically reduced in proband compared to controls; tyw1 deficiency in zebrafish resulted in ectopic neuronal cell migration in the brain and undifferentiated motor neuronal cells in the spinal cord - this was rescued by WT human and zebrafish tyw1 mRNA, but not by mRNA with patients' mutations. In addition, tyw1 knockdown zebrafish showed recuded swimming capacity. Kncokout tyw1-/- mice showed impaired motor function and reduced cognition in behavioural tests.

PMID: 38706838 Sun et al., 2024
Fucntional evidence: Study used brain organoid model and human embryonic stem cells to show that translation efficiency of UUU codon was compromised in TYW1−/− cells. Also, neuron differentiation was impaired when TYW1 was depleted.

TYW1 is not yet associated with a phenotype in OMIM, ClinGen or G2P (accessed 17 Mar 2026).
Sources: Literature
Intellectual disability v9.306 TYW1 Ida Ertmanska changed review comment from: PMID: 34077496 Li et al., 2021
2 Chinese sibs (non-consanguineous parents) reported with comp het TYW1 variants: NM_018264: c.616C>T, p.R206C & c.1166G>A, p. R389Q.
Proband CP_012_1, male - Wechsler Preschool and Primary Scale of Intelligence IQ = 40 at 7 years old (moderate ID);
CP_012_2, older sister - diagnosed with mixed type cerebral palsy (spasticity, dyskinesia), IQ <50 (moderate ID).
Parents confirmed heterozygous for 1 variant each. TYW1:c.616C>T - MAF in gnomADv4 = 0.0004900, including 1 homozygote. TYW1:c.1166G>A MAF in gnomAD v4 = 0.0001559, no homozygotes.

Functional evidence: TYW1 protein levels dramatically reduced in proband compared to controls; tyw1 deficiency in zebrafish resulted in ectopic neuronal cell migration in the brain and undifferentiated motor neuronal cells in the spinal cord - this was rescued by WT human and zebrafish tyw1 mRNA, but not by mRNA with patients' mutations. In addition, tyw1 knockdown zebrafish showed recuded swimming capacity. Kncokout tyw1-/- mice showed impaired motor function and reduced cognition in behavioural tests.

PMID: 38706838 Sun et al., 2024
Fucntional evidence: Study used brain organoid model and human embryonic stem cells to show that translation efficiency of UUU codon was compromised in TYW1−/− cells. Also, neuron differentiation was impaired when TYW1 was depleted.
Sources: Literature; to: PMID: 34077496 Li et al., 2021
2 Chinese sibs (non-consanguineous parents) reported with comp het TYW1 variants: NM_018264: c.616C>T, p.R206C & c.1166G>A, p. R389Q.
Proband CP_012_1, male - Wechsler Preschool and Primary Scale of Intelligence IQ = 40 at 7 years old (moderate ID);
CP_012_2, older sister - diagnosed with mixed type cerebral palsy (spasticity, dyskinesia), IQ <50 (moderate ID).
Parents confirmed heterozygous for 1 variant each. TYW1:c.616C>T - MAF in gnomADv4 = 0.0004900, including 1 homozygote. TYW1:c.1166G>A MAF in gnomAD v4 = 0.0001559, no homozygotes.

Functional evidence: TYW1 protein levels dramatically reduced in proband compared to controls; tyw1 deficiency in zebrafish resulted in ectopic neuronal cell migration in the brain and undifferentiated motor neuronal cells in the spinal cord - this was rescued by WT human and zebrafish tyw1 mRNA, but not by mRNA with patients' mutations. In addition, tyw1 knockdown zebrafish showed recuded swimming capacity. Kncokout tyw1-/- mice showed impaired motor function and reduced cognition in behavioural tests.

PMID: 38706838 Sun et al., 2024
Fucntional evidence: Study used brain organoid model and human embryonic stem cells to show that translation efficiency of UUU codon was compromised in TYW1−/− cells. Also, neuron differentiation was impaired when TYW1 was depleted.

TYW1 is not yet associated with a phenotype in OMIM, ClinGen or G2P (accessed 17 Mar 2026).
Sources: Literature
Intellectual disability v9.306 TYW1 Ida Ertmanska Classified gene: TYW1 as Amber List (moderate evidence)
Intellectual disability v9.306 TYW1 Ida Ertmanska Added comment: Comment on list classification: There is one pedigree reported in literature linking biallelic TYW1 variants to cerebral palsy with intellectual disability. There is also good functional evidence in zebrafish, mouse, and human brain organoids supporting TYW1 role in motor function and cognition. Based on available evidence, this gene can only be rated Amber for now.
Intellectual disability v9.306 TYW1 Ida Ertmanska Gene: tyw1 has been classified as Amber List (Moderate Evidence).
Childhood onset hereditary spastic paraplegia v8.39 TYW1 Ida Ertmanska Classified gene: TYW1 as Amber List (moderate evidence)
Childhood onset hereditary spastic paraplegia v8.39 TYW1 Ida Ertmanska Added comment: Comment on list classification: There is one pedigree reported in literature linking biallelic TYW1 variants to cerebral palsy with intellectual disability. There is also good functional evidence in zebrafish, mouse, and human brain organoids supporting TYW1 role in motor function and cognition. Based on available evidence, this gene can only be rated Amber for now.
Childhood onset hereditary spastic paraplegia v8.39 TYW1 Ida Ertmanska Gene: tyw1 has been classified as Amber List (Moderate Evidence).
Intellectual disability v9.305 TYW1 Ida Ertmanska gene: TYW1 was added
gene: TYW1 was added to Intellectual disability. Sources: Literature
Mode of inheritance for gene: TYW1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TYW1 were set to 34077496
Phenotypes for gene: TYW1 were set to cerebral palsy, MONDO:0006497
Review for gene: TYW1 was set to AMBER
Added comment: PMID: 34077496 Li et al., 2021
2 Chinese sibs (non-consanguineous parents) reported with comp het TYW1 variants: NM_018264: c.616C>T, p.R206C & c.1166G>A, p. R389Q.
Proband CP_012_1, male - Wechsler Preschool and Primary Scale of Intelligence IQ = 40 at 7 years old (moderate ID);
CP_012_2, older sister - diagnosed with mixed type cerebral palsy (spasticity, dyskinesia), IQ <50 (moderate ID).
Parents confirmed heterozygous for 1 variant each. TYW1:c.616C>T - MAF in gnomADv4 = 0.0004900, including 1 homozygote. TYW1:c.1166G>A MAF in gnomAD v4 = 0.0001559, no homozygotes.

Functional evidence: TYW1 protein levels dramatically reduced in proband compared to controls; tyw1 deficiency in zebrafish resulted in ectopic neuronal cell migration in the brain and undifferentiated motor neuronal cells in the spinal cord - this was rescued by WT human and zebrafish tyw1 mRNA, but not by mRNA with patients' mutations. In addition, tyw1 knockdown zebrafish showed recuded swimming capacity. Kncokout tyw1-/- mice showed impaired motor function and reduced cognition in behavioural tests.

PMID: 38706838 Sun et al., 2024
Fucntional evidence: Study used brain organoid model and human embryonic stem cells to show that translation efficiency of UUU codon was compromised in TYW1−/− cells. Also, neuron differentiation was impaired when TYW1 was depleted.
Sources: Literature
Childhood onset hereditary spastic paraplegia v8.38 TYW1 Ida Ertmanska gene: TYW1 was added
gene: TYW1 was added to Childhood onset hereditary spastic paraplegia. Sources: Literature
Mode of inheritance for gene: TYW1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TYW1 were set to 34077496
Phenotypes for gene: TYW1 were set to cerebral palsy, MONDO:0006497
Review for gene: TYW1 was set to AMBER
Added comment: PMID: 34077496 Li et al., 2021
2 Chinese sibs (non-consanguineous parents) reported with comp het TYW1 variants: NM_018264: c.616C>T, p.R206C & c.1166G>A, p. R389Q.
Proband CP_012_1, male - Wechsler Preschool and Primary Scale of Intelligence IQ = 40 at 7 years old (moderate ID);
CP_012_2, older sister - diagnosed with mixed type cerebral palsy (spasticity, dyskinesia), IQ <50 (moderate ID).
Parents confirmed heterozygous for 1 variant each. TYW1:c.616C>T - MAF in gnomADv4 = 0.0004900, including 1 homozygote. TYW1:c.1166G>A MAF in gnomAD v4 = 0.0001559, no homozygotes.

Functional evidence: TYW1 protein levels dramatically reduced in proband compared to controls; tyw1 deficiency in zebrafish resulted in ectopic neuronal cell migration in the brain and undifferentiated motor neuronal cells in the spinal cord - this was rescued by WT human and zebrafish tyw1 mRNA, but not by mRNA with patients' mutations. In addition, tyw1 knockdown zebrafish showed recuded swimming capacity. Kncokout tyw1-/- mice showed impaired motor function and reduced cognition in behavioural tests.

PMID: 38706838 Sun et al., 2024
Fucntional evidence: Study used brain organoid model and human embryonic stem cells to show that translation efficiency of UUU codon was compromised in TYW1−/− cells. Also, neuron differentiation was impaired when TYW1 was depleted.
Sources: Literature
Incontinentia pigmenti v1.4 IKBKG Achchuthan Shanmugasundram Tag currently-ngs-unreportable tag was added to gene: IKBKG.
Structural eye disease v4.40 IKBKG Achchuthan Shanmugasundram Tag currently-ngs-unreportable tag was added to gene: IKBKG.
Mosaic skin disorders - deep sequencing v3.27 IKBKG Achchuthan Shanmugasundram Tag currently-ngs-unreportable tag was added to gene: IKBKG.
Rare genetic inflammatory skin disorders v4.18 IKBKG Achchuthan Shanmugasundram Tag currently-ngs-unreportable tag was added to gene: IKBKG.
Autoinflammatory disorders v2.35 IKBKG Achchuthan Shanmugasundram Tag currently-ngs-unreportable tag was added to gene: IKBKG.
Primary lymphoedema v4.21 IKBKG Achchuthan Shanmugasundram Tag currently-ngs-unreportable tag was added to gene: IKBKG.
Retinal disorders v8.99 IKBKG Achchuthan Shanmugasundram Tag currently-ngs-unreportable tag was added to gene: IKBKG.
Intellectual disability v9.304 IKBKG Achchuthan Shanmugasundram Tag currently-ngs-unreportable tag was added to gene: IKBKG.
Early onset or syndromic epilepsy v8.147 IKBKG Achchuthan Shanmugasundram Tag currently-ngs-unreportable tag was added to gene: IKBKG.
DDG2P v6.426 IKBKG Achchuthan Shanmugasundram Tag currently-ngs-unreportable tag was added to gene: IKBKG.
Fetal anomalies v6.157 IKBKG Achchuthan Shanmugasundram Tag currently-ngs-unreportable tag was added to gene: IKBKG.
Skeletal dysplasia v8.38 IKBKG Achchuthan Shanmugasundram Tag currently-ngs-unreportable tag was added to gene: IKBKG.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.84 IKBKG Achchuthan Shanmugasundram Tag currently-ngs-unreportable tag was added to gene: IKBKG.
Ectodermal dysplasia v4.25 IKBKG Achchuthan Shanmugasundram Tag currently-ngs-unreportable tag was added to gene: IKBKG.
Epidermolysis bullosa and congenital skin fragility v2.13 IKBKG Achchuthan Shanmugasundram Tag currently-ngs-unreportable tag was added to gene: IKBKG.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.39 PABPN1_GCN Ida Ertmanska changed review comment from: PMID: 27858728 Richard et al., 2015
Case report of a male patients with disease onset at age 60 years - slowly progressive OPMD. He presented with dysphagia, mild ptosis (at 83 years), lower limb weakness. CT scan of lower limbs showed a hypodense aspect of glutei, posterior thigh and leg compartment muscles. CK slightly elevated. Muscle biopsy showed PABPN1 intranuclear inclusions. Classical Ala11 (GCN)11 expansion in PABPN1 detected. Dominant (though milder) disease despite harbouring the Ala11 "recessive" allele.

PMID: 28011929 Richard et al., 2017
French cohort of 354 unrelated index cases with Oculopharyngeal muscular dystrophy (OPMD) - an autosomal dominant adult-onset disease characterized by progressive ptosis, dysphagia, and proximal limb weakness. Key findings:
1. Patients with longer expansions have earlier disease onset (range of 11-17, 10 = WT). Earliest onset around age 30-40 years, late onset in 60s-70s.
2. Patients with biallelic variants present with more severe disease.
3. Reported 6 cases with heterozygous Ala11 allele, confirming that Ala11 can also act as a dominant mutation.

PABPN1 is linked to AD Oculopharyngeal muscular dystrophy, OMIM:164300 (OMIM accessed 16 Mar 2026).
Sources: Literature; to: PMID: 27858728 Richard et al., 2015
Case report of a male patients with disease onset at age 60 years - slowly progressive OPMD. He presented with dysphagia, mild ptosis (at 83 years), lower limb weakness. CT scan of lower limbs showed a hypodense aspect of glutei, posterior thigh and leg compartment muscles. CK slightly elevated. Muscle biopsy showed PABPN1 intranuclear inclusions. Classical Ala11 (GCN)11 expansion in PABPN1 detected. Dominant (though milder) disease despite harbouring the Ala11 "recessive" allele.

PMID: 28011929 Richard et al., 2017
French cohort of 354 unrelated index cases with Oculopharyngeal muscular dystrophy (OPMD) - an autosomal dominant adult-onset disease characterized by progressive ptosis, dysphagia, and proximal limb weakness. Key findings:
1. Patients with longer expansions have earlier disease onset (range of 11-17, 10 = WT). Earliest onset around age 30-40 years, late onset in 60s-70s.
2. Patients with biallelic variants present with more severe disease.
3. Reported 6 cases with heterozygous Ala11 allele, confirming that Ala11 can also act as a dominant mutation with low penetrance.

PABPN1 is linked to AD Oculopharyngeal muscular dystrophy, OMIM:164300 (OMIM accessed 16 Mar 2026).
Sources: Literature
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.39 PABPN1_GCN Ida Ertmanska Mode of inheritance for STR: PABPN1_GCN was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.38 PABPN1_GCN Ida Ertmanska PABPN1_CGN was changed to PABPN1_GCN
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.37 PABPN1_CGN Ida Ertmanska Repeated Sequence for PABPN1_CGN was changed from CGN to GCN.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.36 PABPN1_CGN Ida Ertmanska edited their review of STR: PABPN1_CGN: Changed publications to: 27858728, 28011929; Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.36 PABPN1_CGN Ida Ertmanska Publications for STR: PABPN1_CGN were set to
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.35 PABPN1_CGN Ida Ertmanska changed review comment from: Sources: Literature; to: PMID: 27858728 Richard et al., 2015
Case report of a male patients with disease onset at age 60 years - slowly progressive OPMD. He presented with dysphagia, mild ptosis (at 83 years), lower limb weakness. CT scan of lower limbs showed a hypodense aspect of glutei, posterior thigh and leg compartment muscles. CK slightly elevated. Muscle biopsy showed PABPN1 intranuclear inclusions. Classical Ala11 (GCN)11 expansion in PABPN1 detected. Dominant (though milder) disease despite harbouring the Ala11 "recessive" allele.

PMID: 28011929 Richard et al., 2017
French cohort of 354 unrelated index cases with Oculopharyngeal muscular dystrophy (OPMD) - an autosomal dominant adult-onset disease characterized by progressive ptosis, dysphagia, and proximal limb weakness. Key findings:
1. Patients with longer expansions have earlier disease onset (range of 11-17, 10 = WT). Earliest onset around age 30-40 years, late onset in 60s-70s.
2. Patients with biallelic variants present with more severe disease.
3. Reported 6 cases with heterozygous Ala11 allele, confirming that Ala11 can also act as a dominant mutation.

PABPN1 is linked to AD Oculopharyngeal muscular dystrophy, OMIM:164300 (OMIM accessed 16 Mar 2026).
Sources: Literature
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.35 PABPN1_CGN Ida Ertmanska edited their review of STR: PABPN1_CGN: Changed rating: GREEN; Changed publications to: 28011929
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.35 PABPN1_CGN Ida Ertmanska Classified STR: PABPN1_CGN as Amber List (moderate evidence)
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.35 PABPN1_CGN Ida Ertmanska Str: pabpn1_cgn has been classified as Amber List (Moderate Evidence).
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.34 PABPN1_CGN Ida Ertmanska STR: PABPN1_CGN was added
STR: PABPN1_CGN was added to Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies. Sources: Literature
Mode of inheritance for STR: PABPN1_CGN was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for STR: PABPN1_CGN were set to Oculopharyngeal muscular dystrophy, OMIM:164300; oculopharyngeal muscular dystrophy, MONDO:0008116
Review for STR: PABPN1_CGN was set to AMBER
Added comment: Sources: Literature
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.33 PABPN1 Ida Ertmanska Phenotypes for gene: PABPN1 were changed from Oculopharyngeal muscular dystrophy, OMIM:164300 to Oculopharyngeal muscular dystrophy, OMIM:164300; oculopharyngeal muscular dystrophy, MONDO:0008116
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.32 PABPN1 Ida Ertmanska Publications for gene: PABPN1 were set to 16648376; 27858728; 34225694; 36847015
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.31 PABPN1 Ida Ertmanska edited their review of gene: PABPN1: Changed phenotypes to: Oculopharyngeal muscular dystrophy, OMIM:164300, oculopharyngeal muscular dystrophy, MONDO:0008116
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.31 PABPN1 Ida Ertmanska edited their review of gene: PABPN1: Changed publications to: 16648376, 21742497, 34225694, 36847015
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.31 PABPN1 Ida Ertmanska changed review comment from: PMID: 16648376 Robinson et al., 2006
Cohort of 202 patients with tentative diagnosis of Oculopharyngeal muscular dystrophy; only sequenced exon 1 of PABPN1. Reported a case with OPMD (patient A, female, European, disease onset around 61 years) negative for the repeat expansion, heterozygous for PABPN1 c.35G>C; p.Gly12Ala variant. There was a pattern of dominant inheritance in the family (not genotyped).

PMID: 21742497 Robinson et al., 2011
Report of 2 further cases with PABPN1 c.35G>C; p.Gly12Ala and OPMD.

PMID: 34225694 Nishii et al., 2021
Report of a 78 yo woman with oculopharyngeal muscular dystrophy - presented with ptosis and gradually progressive dysphagia (symptom onset at 62 years). A physical examination and muscle imaging (MRI and ultrasound) showed impairment of the tongue, proximal muscles of the upper limbs, and flexor muscles of the lower limbs. EMG of bulbar and facial muscles revealed a myopathic pattern. Her son had the same symptoms (ptosis and dysphasia). Sequencing revealed PABPN1 c.35G > C; p.Gly12Ala point mutation.

PMID: 36847015 Takahashi et al., 2023
Case report - 77 yo male patient with heterozygous PABPN1 c.34G > T (p.Gly12Trp) mutation, no polyalanine expansion detected. He presented with slowly progressive bilateral ptosis, dysphagia, and symmetrical proximal dominant muscle weakness - disease onset around 60 yo. MRI revealed selective fat replacement of the tongue, bilateral adductor magnus, and soleus muscles. Muscle biopsy sample revealed PABPN1-positive aggregates in the myonuclei - reported to be specific to OPMD.

PABPN1 is linked to AD Oculopharyngeal muscular dystrophy, OMIM:164300 (OMIM accessed 16 Mar 2026).
Sources: Literature; to: PMID: 16648376 Robinson et al., 2006
Cohort of 202 patients with tentative diagnosis of Oculopharyngeal muscular dystrophy; only sequenced exon 1 of PABPN1. Reported a case with OPMD (patient A, female, European, disease onset around 61 years) negative for the repeat expansion, heterozygous for PABPN1 c.35G>C; p.Gly12Ala variant. There was a pattern of dominant inheritance in the family (not genotyped).

PMID: 21742497 Robinson et al., 2011
Report of 2 further cases with heterozygous PABPN1 c.35G>C; p.Gly12Ala and OPMD diagnosis.
Case 1 - male, bilateral ptosis and choking at 65 years old; no limb muscle weakness reported.
Case 2 - female, onset of swallowing difficulty around age 60, ptosis onset at age 65 years, muscle weakness reported in 70s. No vacuoles seen on deltoid muscle biopsy.

PMID: 34225694 Nishii et al., 2021
Report of a 78 yo woman with oculopharyngeal muscular dystrophy - presented with ptosis and gradually progressive dysphagia (symptom onset at 62 years). A physical examination and muscle imaging (MRI and ultrasound) showed impairment of the tongue, proximal muscles of the upper limbs, and flexor muscles of the lower limbs. EMG of bulbar and facial muscles revealed a myopathic pattern. Her son had the same symptoms (ptosis and dysphasia). Sequencing revealed PABPN1 c.35G > C; p.Gly12Ala point mutation.

PMID: 36847015 Takahashi et al., 2023
Case report - 77 yo male patient with heterozygous PABPN1 c.34G > T (p.Gly12Trp) mutation, no polyalanine expansion detected. He presented with slowly progressive bilateral ptosis, dysphagia, and symmetrical proximal dominant muscle weakness - disease onset around 60 yo. MRI revealed selective fat replacement of the tongue, bilateral adductor magnus, and soleus muscles. Muscle biopsy sample revealed PABPN1-positive aggregates in the myonuclei - reported to be specific to OPMD.

PABPN1 is linked to AD Oculopharyngeal muscular dystrophy, OMIM:164300 (OMIM accessed 16 Mar 2026).
Sources: Literature
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.31 PABPN1 Ida Ertmanska changed review comment from: Comment on list classification: There are at least 3 unrelated individuals reported in literature with heterozygous point mutations in PABPN1 and Oculopharyngeal muscular dystrophy. While the disease is most often caused by PABPN1 trinucleotide repeats, the recurrent heterozygous PABPN1 p.Gly12Ala mutation results in 13 alanine codons with the same pathogenic effect. Based on available evidence, this gene should be promoted to Green with MOI set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted.; to: Comment on list classification: There are at least 3 unrelated individuals reported in literature with heterozygous point mutations in PABPN1 and Oculopharyngeal muscular dystrophy. While the disease is most often caused by PABPN1 trinucleotide repeats, the recurrent heterozygous PABPN1 p.Gly12Ala mutation results in 13 contiguous alanine codons with the same pathogenic effect. Based on available evidence, this gene should be promoted to Green with MOI set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.31 PABPN1 Ida Ertmanska changed review comment from: PMID: 16648376 Robinson et al., 2006
Cohort of 202 patients with tentative diagnosis of Oculopharyngeal muscular dystrophy; only sequenced exon 1 of PABPN1. Reported a case with OPMD (patient A, female, European, disease onset around 61 years) negative for the repeat expansion, heterozygous for PABPN1 c.35G>C; p.Gly12Ala variant. There was a pattern of dominant inheritance in the family (not genotyped).

PMID: 34225694 Nishii et al., 2021
Report of a 78 yo woman with oculopharyngeal muscular dystrophy - presented with ptosis and gradually progressive dysphagia (symptom onset at 62 years). A physical examination and muscle imaging (MRI and ultrasound) showed impairment of the tongue, proximal muscles of the upper limbs, and flexor muscles of the lower limbs. EMG of bulbar and facial muscles revealed a myopathic pattern. Her son had the same symptoms (ptosis and dysphasia). Sequencing revealed PABPN1 c.35G > C; p.Gly12Ala point mutation.

PMID: 36847015 Takahashi et al., 2023
Case report - 77 yo male patient with heterozygous PABPN1 c.34G > T (p.Gly12Trp) mutation, no polyalanine expansion detected. He presented with slowly progressive bilateral ptosis, dysphagia, and symmetrical proximal dominant muscle weakness - disease onset around 60 yo. MRI revealed selective fat replacement of the tongue, bilateral adductor magnus, and soleus muscles. Muscle biopsy sample revealed PABPN1-positive aggregates in the myonuclei - reported to be specific to OPMD.

PABPN1 is linked to AD Oculopharyngeal muscular dystrophy, OMIM:164300 (OMIM accessed 16 Mar 2026).
Sources: Literature; to: PMID: 16648376 Robinson et al., 2006
Cohort of 202 patients with tentative diagnosis of Oculopharyngeal muscular dystrophy; only sequenced exon 1 of PABPN1. Reported a case with OPMD (patient A, female, European, disease onset around 61 years) negative for the repeat expansion, heterozygous for PABPN1 c.35G>C; p.Gly12Ala variant. There was a pattern of dominant inheritance in the family (not genotyped).

PMID: 21742497 Robinson et al., 2011
Report of 2 further cases with PABPN1 c.35G>C; p.Gly12Ala and OPMD.

PMID: 34225694 Nishii et al., 2021
Report of a 78 yo woman with oculopharyngeal muscular dystrophy - presented with ptosis and gradually progressive dysphagia (symptom onset at 62 years). A physical examination and muscle imaging (MRI and ultrasound) showed impairment of the tongue, proximal muscles of the upper limbs, and flexor muscles of the lower limbs. EMG of bulbar and facial muscles revealed a myopathic pattern. Her son had the same symptoms (ptosis and dysphasia). Sequencing revealed PABPN1 c.35G > C; p.Gly12Ala point mutation.

PMID: 36847015 Takahashi et al., 2023
Case report - 77 yo male patient with heterozygous PABPN1 c.34G > T (p.Gly12Trp) mutation, no polyalanine expansion detected. He presented with slowly progressive bilateral ptosis, dysphagia, and symmetrical proximal dominant muscle weakness - disease onset around 60 yo. MRI revealed selective fat replacement of the tongue, bilateral adductor magnus, and soleus muscles. Muscle biopsy sample revealed PABPN1-positive aggregates in the myonuclei - reported to be specific to OPMD.

PABPN1 is linked to AD Oculopharyngeal muscular dystrophy, OMIM:164300 (OMIM accessed 16 Mar 2026).
Sources: Literature
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.31 PABPN1 Ida Ertmanska edited their review of gene: PABPN1: Changed publications to: 16648376, 34225694, 36847015
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.31 PABPN1 Ida Ertmanska Classified gene: PABPN1 as Amber List (moderate evidence)
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.31 PABPN1 Ida Ertmanska Added comment: Comment on list classification: There are at least 3 unrelated individuals reported in literature with heterozygous point mutations in PABPN1 and Oculopharyngeal muscular dystrophy. While the disease is most often caused by PABPN1 trinucleotide repeats, the recurrent heterozygous PABPN1 p.Gly12Ala mutation results in 13 alanine codons with the same pathogenic effect. Based on available evidence, this gene should be promoted to Green with MOI set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.31 PABPN1 Ida Ertmanska Gene: pabpn1 has been classified as Amber List (Moderate Evidence).
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.30 PABPN1 Ida Ertmanska Tag Q1_26_promote_green tag was added to gene: PABPN1.
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies v5.30 PABPN1 Ida Ertmanska gene: PABPN1 was added
gene: PABPN1 was added to Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies. Sources: Literature
Mode of inheritance for gene: PABPN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PABPN1 were set to 16648376; 27858728; 34225694; 36847015
Phenotypes for gene: PABPN1 were set to Oculopharyngeal muscular dystrophy, OMIM:164300
Review for gene: PABPN1 was set to GREEN
Added comment: PMID: 16648376 Robinson et al., 2006
Cohort of 202 patients with tentative diagnosis of Oculopharyngeal muscular dystrophy; only sequenced exon 1 of PABPN1. Reported a case with OPMD (patient A, female, European, disease onset around 61 years) negative for the repeat expansion, heterozygous for PABPN1 c.35G>C; p.Gly12Ala variant. There was a pattern of dominant inheritance in the family (not genotyped).

PMID: 34225694 Nishii et al., 2021
Report of a 78 yo woman with oculopharyngeal muscular dystrophy - presented with ptosis and gradually progressive dysphagia (symptom onset at 62 years). A physical examination and muscle imaging (MRI and ultrasound) showed impairment of the tongue, proximal muscles of the upper limbs, and flexor muscles of the lower limbs. EMG of bulbar and facial muscles revealed a myopathic pattern. Her son had the same symptoms (ptosis and dysphasia). Sequencing revealed PABPN1 c.35G > C; p.Gly12Ala point mutation.

PMID: 36847015 Takahashi et al., 2023
Case report - 77 yo male patient with heterozygous PABPN1 c.34G > T (p.Gly12Trp) mutation, no polyalanine expansion detected. He presented with slowly progressive bilateral ptosis, dysphagia, and symmetrical proximal dominant muscle weakness - disease onset around 60 yo. MRI revealed selective fat replacement of the tongue, bilateral adductor magnus, and soleus muscles. Muscle biopsy sample revealed PABPN1-positive aggregates in the myonuclei - reported to be specific to OPMD.

PABPN1 is linked to AD Oculopharyngeal muscular dystrophy, OMIM:164300 (OMIM accessed 16 Mar 2026).
Sources: Literature
Intellectual disability v9.304 PPP2R2B Achchuthan Shanmugasundram Tag Q1_25_ promote_green was removed from gene: PPP2R2B.
Intracerebral calcification disorders v1.37 JAM2 Ida Ertmanska reviewed gene: JAM2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31851307, 32142645; Phenotypes: Basal ganglia calcification, idiopathic, 8, autosomal recessive, OMIM:618824; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intracerebral calcification disorders v1.37 JAM2 Ida Ertmanska Classified gene: JAM2 as Green List (high evidence)
Intracerebral calcification disorders v1.37 JAM2 Ida Ertmanska Gene: jam2 has been classified as Green List (High Evidence).
Ataxia and cerebellar anomalies - narrow panel v8.69 JAM2 Ida Ertmanska Classified gene: JAM2 as Amber List (moderate evidence)
Ataxia and cerebellar anomalies - narrow panel v8.69 JAM2 Ida Ertmanska Gene: jam2 has been classified as Amber List (Moderate Evidence).
Ataxia and cerebellar anomalies - narrow panel v8.68 JAM2 Ida Ertmanska commented on gene: JAM2: Comment on list classification: There are more than 3 unrelated individuals reported in literature with childhood-onset brain calcification and biallelic JAM2 variants, presenting with a cerebellar syndrome (ataxia, dysarthria). Hence, JAM2 should be promoted to Green for Ataxia and cerebellar anomalies - narrow panel.
Hereditary ataxia with onset in adulthood v8.28 JAM2 Ida Ertmanska Classified gene: JAM2 as Amber List (moderate evidence)
Hereditary ataxia with onset in adulthood v8.28 JAM2 Ida Ertmanska Added comment: Comment on list classification: There are more than 3 unrelated individuals reported in literature with adult-onset brain calcification and biallelic JAM2 variants, presenting with a cerebellar syndrome (ataxia, dysarthria). Hence, JAM2 should be promoted to Green for Hereditary ataxia with onset in adulthood.
Hereditary ataxia with onset in adulthood v8.28 JAM2 Ida Ertmanska Gene: jam2 has been classified as Amber List (Moderate Evidence).
Retinal disorders v8.99 AP5M1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: AP5M1.
Tag Q1_25_ promote_green was removed from gene: AP5M1.
Ataxia and cerebellar anomalies - narrow panel v8.68 JAM2 Ida Ertmanska gene: JAM2 was added
gene: JAM2 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: Literature
Q1_26_promote_green tags were added to gene: JAM2.
Mode of inheritance for gene: JAM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: JAM2 were set to 31851307; 32142645
Phenotypes for gene: JAM2 were set to Basal ganglia calcification, idiopathic, 8, autosomal recessive, OMIM:618824
Review for gene: JAM2 was set to GREEN
Added comment: PMID: 31851307 Cen et al., 2020
Reported 3 unrelated families with primary familial brain calcification. Probands harboured biallelic JAM2 variants: homozygous c.140delT, p.L48Ter; homozygous c.1A>G, p.M1? and compound heterozygous mutations [c.504G>C, p.W168C & c.(67+1_68-1)_(394+1_395-1), p.Y23_V131delinsL]. The clinical phenotypes of the four patients included parkinsonism (3/4), dysarthria (3/4), seizures (1/4), and asymptomatic at the time of report (1 patient at age 37 years); disease onset ages: 20-38 years. 4/4 patients presented with severe calcifications in the cortex in addition to extensive calcifications in multiple brain areas.

PMID: 32142645 Schottlaender et al., 2023
Report of 7 individuals from 4 families with primary familial brain calcification. Detected biallelic JAM2 variants: homozygous c.685C>T, p.Arg229Ter (2 families); comp het c.395−1dupG, c.323G>A & IVS4-1dupG, p.Arg108His; homozygous c.177_180delCAGA, p.Arg60Ter.
Age of onset: childhood (3/7), teenage (2/7), 20s-30s (2/7).
Phenotype: cerebellar syndrome (6/7), Parkinsonism (5/7), dystonia (3/7), cognitive decline (5/6 assessed), brain calcification (7/7).

Functional evidence: JAM2 variants lead to reduction of JAM2 mRNA expression and absence of JAM2 protein in patient’s fibroblasts; human phenotype of brain calcification is replicated in the jam2 complete knockout mouse (jam2 KO).

JAM2 is associated with Basal ganglia calcification, idiopathic, 8, autosomal recessive, OMIM:618824 (OMIM accesed 16th Mar 2026).
Sources: Literature
Hereditary ataxia with onset in adulthood v8.27 JAM2 Ida Ertmanska gene: JAM2 was added
gene: JAM2 was added to Hereditary ataxia with onset in adulthood. Sources: Literature
Q1_26_promote_green tags were added to gene: JAM2.
Mode of inheritance for gene: JAM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: JAM2 were set to 31851307; 32142645
Phenotypes for gene: JAM2 were set to Basal ganglia calcification, idiopathic, 8, autosomal recessive, OMIM:618824
Review for gene: JAM2 was set to GREEN
Added comment: PMID: 31851307 Cen et al., 2020
Reported 3 unrelated families with primary familial brain calcification. Probands harboured biallelic JAM2 variants: homozygous c.140delT, p.L48Ter; homozygous c.1A>G, p.M1? and compound heterozygous mutations [c.504G>C, p.W168C & c.(67+1_68-1)_(394+1_395-1), p.Y23_V131delinsL]. The clinical phenotypes of the four patients included parkinsonism (3/4), dysarthria (3/4), seizures (1/4), and asymptomatic at the time of report (1 patient at age 37 years); disease onset ages: 20-38 years. 4/4 patients presented with severe calcifications in the cortex in addition to extensive calcifications in multiple brain areas.

PMID: 32142645 Schottlaender et al., 2023
Report of 7 individuals from 4 families with primary familial brain calcification. Detected biallelic JAM2 variants: homozygous c.685C>T, p.Arg229Ter (2 families); comp het c.395−1dupG, c.323G>A & IVS4-1dupG, p.Arg108His; homozygous c.177_180delCAGA, p.Arg60Ter.
Age of onset: childhood (3/7), teenage (2/7), 20s-30s (2/7).
Phenotype: cerebellar syndrome (6/7), Parkinsonism (5/7), dystonia (3/7), cognitive decline (5/6 assessed), brain calcification (7/7).

Functional evidence: JAM2 variants lead to reduction of JAM2 mRNA expression and absence of JAM2 protein in patient’s fibroblasts; human phenotype of brain calcification is replicated in the jam2 complete knockout mouse (jam2 KO).

JAM2 is associated with Basal ganglia calcification, idiopathic, 8, autosomal recessive, OMIM:618824 (OMIM accesed 16th Mar 2026).
Sources: Literature
White matter disorders and cerebral calcification - narrow panel v7.17 JAM2 Ida Ertmanska Classified gene: JAM2 as Amber List (moderate evidence)
White matter disorders and cerebral calcification - narrow panel v7.17 JAM2 Ida Ertmanska Added comment: Comment on list classification: There are more than 3 unrelated individuals reported in literature with biallelic JAM2 variants and cerebral calcification, with onset in childhood or early adulthood. Common symptoms included parkinsonism, cognitive decline, cerebellar syndrome, and dysarthria. Knockout mouse model recapitulated the human phenotype. Based on available evidence, JAM2 should be updated to Green at the next GMS update.
White matter disorders and cerebral calcification - narrow panel v7.17 JAM2 Ida Ertmanska Gene: jam2 has been classified as Amber List (Moderate Evidence).
White matter disorders and cerebral calcification - narrow panel v7.16 JAM2 Ida Ertmanska gene: JAM2 was added
gene: JAM2 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Literature
Q1_26_promote_green tags were added to gene: JAM2.
Mode of inheritance for gene: JAM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: JAM2 were set to 31851307; 32142645
Phenotypes for gene: JAM2 were set to Basal ganglia calcification, idiopathic, 8, autosomal recessive, OMIM:618824
Review for gene: JAM2 was set to GREEN
Added comment: PMID: 31851307 Cen et al., 2020
Reported 3 unrelated families with primary familial brain calcification. Probands harboured biallelic JAM2 variants: homozygous c.140delT, p.L48Ter; homozygous c.1A>G, p.M1? and compound heterozygous mutations [c.504G>C, p.W168C & c.(67+1_68-1)_(394+1_395-1), p.Y23_V131delinsL]. The clinical phenotypes of the four patients included parkinsonism (3/4), dysarthria (3/4), seizures (1/4), and asymptomatic at the time of report (1 patient at age 37 years); disease onset ages: 20-38 years. 4/4 patients presented with severe calcifications in the cortex in addition to extensive calcifications in multiple brain areas.

PMID: 32142645 Schottlaender et al., 2023
Report of 7 individuals from 4 families with primary familial brain calcification. Detected biallelic JAM2 variants: homozygous c.685C>T, p.Arg229Ter (2 families); comp het c.395−1dupG, c.323G>A & IVS4-1dupG, p.Arg108His; homozygous c.177_180delCAGA, p.Arg60Ter.
Age of onset: childhood (3/7), teenage (2/7), 20s-30s (2/7).
Phenotype: cerebellar syndrome (6/7), Parkinsonism (5/7), dystonia (3/7), cognitive decline (5/6 assessed), brain calcification (7/7).

Functional evidence: JAM2 variants lead to reduction of JAM2 mRNA expression and absence of JAM2 protein in patient’s fibroblasts; human phenotype of brain calcification is replicated in the jam2 complete knockout mouse (jam2 KO).

JAM2 is associated with Basal ganglia calcification, idiopathic, 8, autosomal recessive, OMIM:618824 (OMIM accesed 16th Mar 2026).
Sources: Literature
Adult onset neurodegenerative disorder v8.18 JAM2 Ida Ertmanska changed review comment from: Comment on list classification: There are more than 3 unrelated individuals reported in literature with brain calcifications and biallelic JAM2 variants. Common features included parkinsonism, cognitive decline, cerebellar syndrome, and dysarthria. Knockout mouse model recapitulated the human phenotype. Based on available evidence, JAM2 should be updated to Green at the next GMS update.; to: Comment on list classification: There are more than 3 unrelated individuals reported in literature with brain calcifications and biallelic JAM2 variants. Common symptoms included parkinsonism, cognitive decline, cerebellar syndrome, and dysarthria. Knockout mouse model recapitulated the human phenotype. Based on available evidence, JAM2 should be updated to Green at the next GMS update.
Adult onset neurodegenerative disorder v8.18 JAM2 Ida Ertmanska Phenotypes for gene: JAM2 were changed from Basal ganglia calcification 7, 618317; Primary familial brain calcification; Fahr syndrome to Basal ganglia calcification, idiopathic, 8, autosomal recessive, OMIM:618824; basal ganglia calcification, idiopathic, 8, autosomal recessive, MONDO:0032938; Fahr syndrome
Adult onset neurodegenerative disorder v8.17 JAM2 Ida Ertmanska Classified gene: JAM2 as Amber List (moderate evidence)
Adult onset neurodegenerative disorder v8.17 JAM2 Ida Ertmanska Added comment: Comment on list classification: There are more than 3 unrelated individuals reported in literature with brain calcifications and biallelic JAM2 variants. Common features included parkinsonism, cognitive decline, cerebellar syndrome, and dysarthria. Knockout mouse model recapitulated the human phenotype. Based on available evidence, JAM2 should be updated to Green at the next GMS update.
Adult onset neurodegenerative disorder v8.17 JAM2 Ida Ertmanska Gene: jam2 has been classified as Amber List (Moderate Evidence).
Adult onset neurodegenerative disorder v8.16 JAM2 Ida Ertmanska Tag Q1_26_promote_green tag was added to gene: JAM2.
Adult onset neurodegenerative disorder v8.16 JAM2 Ida Ertmanska edited their review of gene: JAM2: Changed rating: GREEN; Changed publications to: 31851307, 32142645; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v8.16 JAM2 Ida Ertmanska changed review comment from: PMID: 31851307 Cen et al., 2020; to: PMID: 31851307 Cen et al., 2020
Reported 3 unrelated families with primary familial brain calcification. Probands harboured biallelic JAM2 variants: homozygous c.140delT, p.L48Ter; homozygous c.1A>G, p.M1? and compound heterozygous mutations [c.504G>C, p.W168C & c.(67+1_68-1)_(394+1_395-1), p.Y23_V131delinsL]. The clinical phenotypes of the four patients included parkinsonism (3/4), dysarthria (3/4), seizures (1/4), and asymptomatic at the time of report (1 patient at age 37 years); disease onset ages: 20-38 years. 4/4 patients presented with severe calcifications in the cortex in addition to extensive calcifications in multiple brain areas.

PMID: 32142645 Schottlaender et al., 2023
Report of 7 individuals from 4 families with primary familial brain calcification. Detected biallelic JAM2 variants: homozygous c.685C>T, p.Arg229Ter (2 families); comp het c.395−1dupG, c.323G>A & IVS4-1dupG, p.Arg108His; homozygous c.177_180delCAGA, p.Arg60Ter.
Age of onset: childhood (3/7), teenage (2/7), 20s-30s (2/7).
Phenotype: cerebellar syndrome (6/7), Parkinsonism (5/7), dystonia (3/7), cognitive decline (5/6 assessed), brain calcification (7/7).

Functional evidence: JAM2 variants lead to reduction of JAM2 mRNA expression and absence of JAM2 protein in patient’s fibroblasts; human phenotype of brain calcification is replicated in the jam2 complete knockout mouse (jam2 KO).

JAM2 is associated with Basal ganglia calcification, idiopathic, 8, autosomal recessive, OMIM:618824 (OMIM accesed 16th Mar 2026).
Childhood onset hereditary spastic paraplegia v8.37 SPTSSA Achchuthan Shanmugasundram changed review comment from: Comment on mode of inheritance: There are three unrelated published patient cases and an additional patient suggested by an NHS colleague are available in support of the association of monoallelic Thr51Ile variant with Spastic paraplegia 90A, autosomal dominant (MIM #620416). However, there is only one patient reported with biallelic SPTSSA variant. There is also functional evidence available for the variant and homozygous mouse knock-out model available.

The MOI should be set to 'BIALLELIC, autosomal or pseudoautosomal' with the current evidence.; to: Comment on mode of inheritance: There are three unrelated published patient cases and an additional patient suggested by an NHS colleague are available in support of the association of monoallelic Thr51Ile variant with Spastic paraplegia 90A, autosomal dominant (MIM #620416). However, there is only one patient reported with biallelic SPTSSA variant. There is also functional evidence available for the variant and homozygous mouse knock-out model available.

The MOI should be set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' with the current evidence.
Adult onset neurodegenerative disorder v8.16 JAM2 Ida Ertmanska reviewed gene: JAM2: Rating: ; Mode of pathogenicity: None; Publications: 31851307, 37446066; Phenotypes: Basal ganglia calcification, idiopathic, 8, autosomal recessive, OMIM:618824; Mode of inheritance: None
Primary lymphoedema v4.21 PLXNB2 Sahar Mansour gene: PLXNB2 was added
gene: PLXNB2 was added to Primary lymphoedema. Sources: Literature
Mode of inheritance for gene: PLXNB2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLXNB2 were set to 38458752:
Phenotypes for gene: PLXNB2 were set to amelogenesis imperfecta; hearing loss; intellectual disability; lymphoedema
Penetrance for gene: PLXNB2 were set to unknown
Mode of pathogenicity for gene: PLXNB2 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: PLXNB2 was set to AMBER
Added comment: We have seen three families with pathogenic variants in this gene and primary lymphoedema
Sources: Literature
Paediatric disorders - additional genes v7.35 DDR2 Ida Ertmanska changed review comment from: Comment on list classification: There are at least 6 individuals reported in literature with heterozygous missense variants in DDR2 and Warburg-Cinotti syndrome - with the main feature being contractures. DDR2-related recessive disease mainly features skeletal dysplasia; DDR2 is already included on R27 with BIALLELIC MOI through skeletal dysplasia panel. Hence, DDR2 should be updated to Green for Paediatric disorders - additional genes with MOI MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted.; to: Comment on list classification: There are at least 6 individuals reported in literature with heterozygous missense variants in DDR2 and Warburg-Cinotti syndrome - with the main feature being contractures. DDR2-related recessive disease mainly features skeletal dysplasia; DDR2 is already included on R27 with BIALLELIC MOI through skeletal dysplasia panel. To ensure inclusion of Warburg-Cinotti syndrome on R27, DDR2 should be updated to Green for Paediatric disorders - additional genes with MOI MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted.
Paediatric disorders - additional genes v7.35 DDR2 Ida Ertmanska Classified gene: DDR2 as Amber List (moderate evidence)
Paediatric disorders - additional genes v7.35 DDR2 Ida Ertmanska Added comment: Comment on list classification: There are at least 6 individuals reported in literature with heterozygous missense variants in DDR2 and Warburg-Cinotti syndrome - with the main feature being contractures. DDR2-related recessive disease mainly features skeletal dysplasia; DDR2 is already included on R27 with BIALLELIC MOI through skeletal dysplasia panel. Hence, DDR2 should be updated to Green for Paediatric disorders - additional genes with MOI MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted.
Paediatric disorders - additional genes v7.35 DDR2 Ida Ertmanska Gene: ddr2 has been classified as Amber List (Moderate Evidence).
Paediatric disorders - additional genes v7.34 DDR2 Ida Ertmanska gene: DDR2 was added
gene: DDR2 was added to Paediatric disorders - additional genes. Sources: Literature
Q1_26_promote_green tags were added to gene: DDR2.
Mode of inheritance for gene: DDR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DDR2 were set to 30449416
Phenotypes for gene: DDR2 were set to Warburg-Cinotti syndrome, OMIM:618175
Review for gene: DDR2 was set to GREEN
Added comment: 30449416 Xu et al,, 2018
6 patients from 4 unrelated families, 2 previously reported. All patients were heterozygous for one of the recurring DDR2 variants: c.1829T>C (p.Leu610Pro) or c.2219A>G (p.Tyr740Cys).
Phenotypic spectrum: contractures (6/6, variable severity), corneal vascularization (5/6), skin with little subcutaneous tissue (4/6), keloid-like plaques (4/6), loss of toes/toenails (4/6), joint swellings (4/6), and other less penetrant features.

This gene is associated with AD Warburg-Cinotti syndrome 618175 and AR Spondylometaepiphyseal dysplasia, short limb-hand type 271665 (OMIM accessed 13th Mar 2026).
Sources: Literature
Arthrogryposis v9.31 DDR2 Ida Ertmanska edited their review of gene: DDR2: Changed phenotypes to: Warburg-Cinotti syndrome, OMIM:618175
Arthrogryposis v9.31 DDR2 Ida Ertmanska Classified gene: DDR2 as Amber List (moderate evidence)
Arthrogryposis v9.31 DDR2 Ida Ertmanska Added comment: Comment on list classification: There are at least 6 individuals reported in literature with heterozygous missense variants in DDR2 and Warburg-Cinotti syndrome - with the main feature being contractures. Contractures are not a feature of DDR2-related recessive disease. Hence, DDR2 should be updated to Green at the next GMS update with MOI MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted.
Arthrogryposis v9.31 DDR2 Ida Ertmanska Gene: ddr2 has been classified as Amber List (Moderate Evidence).
Arthrogryposis v9.30 DDR2 Ida Ertmanska gene: DDR2 was added
gene: DDR2 was added to Arthrogryposis. Sources: Literature
Q1_26_promote_green tags were added to gene: DDR2.
Mode of inheritance for gene: DDR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DDR2 were set to 30449416
Review for gene: DDR2 was set to GREEN
Added comment: 30449416 Xu et al,, 2018
6 patients from 4 unrelated families, 2 previously reported. All patients were heterozygous for one of the recurring DDR2 variants: c.1829T>C (p.Leu610Pro) or c.2219A>G (p.Tyr740Cys).
Phenotypic spectrum: contractures (6/6, variable severity), corneal vascularization (5/6), skin with little subcutaneous tissue (4/6), keloid-like plaques (4/6), loss of toes/toenails (4/6), joint swellings (4/6), and other less penetrant features.

This gene is associated with AD Warburg-Cinotti syndrome 618175 and AR Spondylometaepiphyseal dysplasia, short limb-hand type 271665 (OMIM accessed 13th Mar 2026).
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v8.84 RNU4ATAC Ida Ertmanska changed review comment from: PMID: 26522830 Merico et al., 2015
6 cases with Roifman syndrome from 4 unrelated families (English, Italian, Lebanese, Albanian). All 6 had history of repeat infections.

PMID: 28623346 Bogaert et al., 2017
Report of two siblings that presented with a phenotype resembling early-onset common variable immunodeficiency - extra-immunological characteristics were not apparent at that time. Additional features were diagnosed later, including skeletal and organ anomalies and mild facial dysmorphism. Whole exome sequencing revealed c.13 C > T and c.116 A > T RNU4ATAC variants, which is consistent with diagnosis of Roifman syndrome.

PMID: 29391254 Heremans et al., 2018
3 patients from 2 unrelated kindreds harboring compound heterozygous or homozygous stem II variants in RNU4ATAC. All patients have a common phenotype of moderate psychomotor delay and autism spectrum disorder, retinal dystrophy with hypovascularization, severe growth retardation, spondyloepiphysial dysplasia with irregularly shaped vertebral bodies with platyspondyly and flattened proximal femoral epiphyses, pruritic ichthyosis-like skin rash, brachydactyly, hyperlaxity, hypotonia, and hepatosplenomegaly.
All 3 patients have hypogammaglobulinemia and B-cell lymphopenia, and they experience recurrent viral infections, necessitating immunoglobulin substitution therapy. P2 had mucocutaneous Herpes simplex infection, and P3 presented a pneumococcal sepsis on discontinuation of therapy. Study showed abnormal differentiation of B cells and megakaryocytes in the patients.

PMID: 33059947 Hagiwara et al., 2020
18-year-old woman exhibiting congenital dwarfism and microcephaly with structural brain anomaly. She suffered human herpesvirus 6 (HHV-6)-associated acute necrotizing encephalopathy at age one, resulting in severe psychomotor disabilities. Genetic analysis revealed comp het variants in RNU4ATAC (NR_023343.1:n.[50G > A];[55G > A]). Immunological findings showed decreases in total lymphocytes, CD4+ T cells, and T cell regenerative activity, and little response to vaccinations.

RNU4ATAC is associated with multiple AR conditions in OMIM: Lowry-Wood syndrome, MIM:226960; Microcephalic osteodysplastic primordial dwarfism, type I, MIM:210710; Roifman syndrome, OMIM:616651. Only Roifman syndrome features immunodeficiency.; to: PMID: 26522830 Merico et al., 2015
6 cases with Roifman syndrome from 4 unrelated families (English, Italian, Lebanese, Albanian). All 6 had history of repeat infections.

PMID: 28623346 Bogaert et al., 2017
Report of two siblings that presented with a phenotype resembling early-onset common variable immunodeficiency - extra-immunological characteristics were not apparent at that time. Additional features were diagnosed later, including skeletal and organ anomalies and mild facial dysmorphism. Whole exome sequencing revealed c.13 C > T and c.116 A > T RNU4ATAC variants, which is consistent with diagnosis of Roifman syndrome.

PMID: 29391254 Heremans et al., 2018
3 patients from 2 unrelated kindreds harboring compound heterozygous or homozygous stem II variants in RNU4ATAC. All patients have a common phenotype of moderate psychomotor delay and autism spectrum disorder, retinal dystrophy with hypovascularization, severe growth retardation, spondyloepiphysial dysplasia with irregularly shaped vertebral bodies with platyspondyly and flattened proximal femoral epiphyses, pruritic ichthyosis-like skin rash, brachydactyly, hyperlaxity, hypotonia, and hepatosplenomegaly.
All 3 patients have hypogammaglobulinemia and B-cell lymphopenia, and they experience recurrent viral infections, necessitating immunoglobulin substitution therapy. P2 had mucocutaneous Herpes simplex infection, and P3 presented a pneumococcal sepsis on discontinuation of therapy. Study showed abnormal differentiation of B cells and megakaryocytes in the patients.

PMID: 33059947 Hagiwara et al., 2020
18-year-old woman exhibiting congenital dwarfism and microcephaly with structural brain anomaly. She suffered human herpesvirus 6 (HHV-6)-associated acute necrotizing encephalopathy at age one, resulting in severe psychomotor disabilities. Genetic analysis revealed comp het variants in RNU4ATAC (NR_023343.1:n.[50G > A];[55G > A]). Immunological findings showed decreases in total lymphocytes, CD4+ T cells, and T cell regenerative activity, and little response to vaccinations.

MedRxiv preprint Johnson et al., 2025 doi: https://doi.org/10.1101/2025.09.12.25335567
identified 19 individuals with early-onset diabetes (diagnosed <5 years) and additional clinical features who had biallelic pathogenic variants in the novel disease gene RNU6ATAC (n=7) or in RNU4ATAC (n=12). 12/19 had additional immune features of immune dysregulation.

RNU4ATAC is associated with multiple AR conditions in OMIM: Lowry-Wood syndrome, MIM:226960; Microcephalic osteodysplastic primordial dwarfism, type I, MIM:210710; Roifman syndrome, OMIM:616651. Only Roifman syndrome features immunodeficiency.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.84 RNU4ATAC Ida Ertmanska Publications for gene: RNU4ATAC were set to 26522830; 32086639; 21474760; 32048120
Primary immunodeficiency or monogenic inflammatory bowel disease v8.83 RNU4ATAC Ida Ertmanska Tag Q1_26_promote_green tag was added to gene: RNU4ATAC.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.83 RNU4ATAC Ida Ertmanska Classified gene: RNU4ATAC as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v8.83 RNU4ATAC Ida Ertmanska Added comment: Comment on list classification: Immunodeficiency is a consistent finding in RNU4ATAC-related Roifman syndrome. In some cases, it may be the sole presenting feature, as other characteristics become apparent later. There are more than 3 unrelated cases reported in literature with biallelic RNU4ATAC variants and syndromic immunodeficiency, Hence, this gene should be promoted to Green at the next GMS update.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.83 RNU4ATAC Ida Ertmanska Gene: rnu4atac has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v8.82 RNU4ATAC Ida Ertmanska reviewed gene: RNU4ATAC: Rating: GREEN; Mode of pathogenicity: None; Publications: 26522830, 28623346, 29391254, 33059947; Phenotypes: Roifman syndrome, OMIM:616651; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v8.37 FBXO31 Ida Ertmanska changed review comment from: Comment on list classification: There are 3 unrelated cases reported in literature with a recurrent de novo heterozygous missense variant in FBXO31, presenting with childhood-onset spasticity, dystonia, ID, and cerebral abnormalities on MRI. Hence, this gene can be promoted to Green at the next GMS update, with MOI set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted.
; to: Comment on list classification: There are 3 unrelated cases reported in literature with a recurrent de novo heterozygous missense variant in FBXO31, presenting with childhood-onset spasticity, dystonia, ID, with or without cerebral abnormalities on MRI. Hence, this gene can be promoted to Green at the next GMS update, with MOI set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted.
Childhood onset hereditary spastic paraplegia v8.37 FBXO31 Ida Ertmanska Tag Q1_26_promote_green tag was added to gene: FBXO31.
Childhood onset hereditary spastic paraplegia v8.37 FBXO31 Ida Ertmanska changed review comment from: Comment on list classification: There are 3 unrelated cases reported in literature with a recurrent de novo heterozygous missense variant in FBXO31, presenting with childhood-onset spasticity, dystonia, ID, and cerebral abnormalities on MRI. Hence, this gene can be promoted to Green at the next GMS update.; to: Comment on list classification: There are 3 unrelated cases reported in literature with a recurrent de novo heterozygous missense variant in FBXO31, presenting with childhood-onset spasticity, dystonia, ID, and cerebral abnormalities on MRI. Hence, this gene can be promoted to Green at the next GMS update, with MOI set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted.
Childhood onset hereditary spastic paraplegia v8.37 FBXO31 Ida Ertmanska changed review comment from: Comment on list classification: There are 3 unrelated cases reported in literature with a recurrent de novo missense variant in FBXO31, presenting with childhood-onset spasticity, dystonia, ID, and cerebral abnormalities on MRI. Hence, this gene can be promoted to Green at the next GMS update.; to: Comment on list classification: There are 3 unrelated cases reported in literature with a recurrent de novo heterozygous missense variant in FBXO31, presenting with childhood-onset spasticity, dystonia, ID, and cerebral abnormalities on MRI. Hence, this gene can be promoted to Green at the next GMS update.
Childhood onset hereditary spastic paraplegia v8.37 FBXO31 Ida Ertmanska Classified gene: FBXO31 as Amber List (moderate evidence)
Childhood onset hereditary spastic paraplegia v8.37 FBXO31 Ida Ertmanska Added comment: Comment on list classification: There are 3 unrelated cases reported in literature with a recurrent de novo missense variant in FBXO31, presenting with childhood-onset spasticity, dystonia, ID, and cerebral abnormalities on MRI. Hence, this gene can be promoted to Green at the next GMS update.
Childhood onset hereditary spastic paraplegia v8.37 FBXO31 Ida Ertmanska Gene: fbxo31 has been classified as Amber List (Moderate Evidence).
Intellectual disability v9.304 FBXO31 Ida Ertmanska Tag Q1_26_MOI was removed from gene: FBXO31.
Childhood onset hereditary spastic paraplegia v8.36 FBXO31 Ida Ertmanska gene: FBXO31 was added
gene: FBXO31 was added to Childhood onset hereditary spastic paraplegia. Sources: Literature
Mode of inheritance for gene: FBXO31 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBXO31 were set to 32989326; 33675180
Phenotypes for gene: FBXO31 were set to neurodevelopmental disorder, MONDO:0700092
Review for gene: FBXO31 was set to GREEN
Added comment: PMID: 32989326 Jin et al., 2020
Report of 2 unrelated patients with the same de novo FBXO31 mutation 16:87367889:C:T, p.Asp334Asn. Disease onset was under age two years.
F218-003 - Female, European, presented with spastic diplegia, as well as Esotropia, ID, dysarthria, mixed receptive/expressive language disorder, ADHD, cleft palate, intestinal malrotation and midgut volvulus.
F699-003 - Male, European, presented with spastic paraplegia, as well as Ventricular dilation and thin corpus callosum, ID, attention deficit, anxiety, language impairments, strabismus, severe constipation.

PMID: 33675180 Dzinovic et al., 2021
Report of a 9yo boy of Slovakian descent, with a de novo FBXO31 variant c.1000G>A (p.Asp334Asn) - trio WES. He presented with complex, non‐progressive movement‐disorder syndrome dominated by spasticity and dystonia. Brain MRI showed bilateral occipital and parietal white‐matter volume reduction, irregular white‐matter dysmyelination. Intellectual disability estimated at Moderate severity (no IQ assessment; loss of speech at the age of 1.5 years, receptive language disorder)
Sources: Literature
Intellectual disability v9.304 FBXO31 Ida Ertmanska Tag Q1_26_MOI tag was added to gene: FBXO31.
Intellectual disability v9.304 FBXO31 Ida Ertmanska changed review comment from: Monoallelic cases:

PMID: 32989326 Jin et al., 2020
Report of 2 unrelated patients with the same de novo FBXO31 mutation 16:87367889:C:T, p.Asp334Asn.
F218-003 - Female, European, presented with spastic diplegia, as well as Esotropia, ID, dysarthria, mixed receptive/expressive language disorder, ADHD, cleft palate, intestinal malrotation and midgut volvulus.
F699-003 - Male, European, presented with spastic paraplegia, as well as Ventricular dilation and thin corpus callosum, ID, attention deficit, anxiety, language impairments, strabismus, severe constipation

PMID: 33675180 Dzinovic et al., 2021
Report of a 9yo boy of Slovakian descent, with a de novo FBXO31 variant c.1000G>A (p.Asp334Asn) - trio WES. He presented with complex, non‐progressive movement‐disorder syndrome dominated by spasticity and dystonia. Brain MRI showed bilateral occipital and parietal white‐matter volume reduction, irregular white‐matter dysmyelination.

FBXO31 p.Asp334Asn is not reported in gnomAD v4.1.0. Revel prediction is Uncertain (0.46).; to: Monoallelic cases:

PMID: 32989326 Jin et al., 2020
Report of 2 unrelated patients with the same de novo FBXO31 mutation 16:87367889:C:T, p.Asp334Asn. Disease onset was under age two years.
F218-003 - Female, European, presented with spastic diplegia, as well as Esotropia, ID, dysarthria, mixed receptive/expressive language disorder, ADHD, cleft palate, intestinal malrotation and midgut volvulus.
F699-003 - Male, European, presented with spastic paraplegia, as well as Ventricular dilation and thin corpus callosum, ID, attention deficit, anxiety, language impairments, strabismus, severe constipation.

PMID: 33675180 Dzinovic et al., 2021
Report of a 9yo boy of Slovakian descent, with a de novo FBXO31 variant c.1000G>A (p.Asp334Asn) - trio WES. He presented with complex, non‐progressive movement‐disorder syndrome dominated by spasticity and dystonia. Brain MRI showed bilateral occipital and parietal white‐matter volume reduction, irregular white‐matter dysmyelination. Intellectual disability estimated at Moderate severity (no IQ assessment; loss of speech at the age of 1.5 years, receptive language disorder)

FBXO31 p.Asp334Asn is not reported in gnomAD v4.1.0. Revel prediction is Uncertain (0.46).
Intellectual disability v9.304 FBXO31 Ida Ertmanska reviewed gene: FBXO31: Rating: GREEN; Mode of pathogenicity: None; Publications: 32989326, 33675180; Phenotypes: neurodevelopmental disorder, MONDO:0700092; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Malformations of cortical development v7.38 PPP2R1A Ida Ertmanska changed review comment from: PMID: 33106617 Lenaerts et al., 2021
Report of 30 individuals with 16 different de novo variants in PPP2R1A. Shared phenotype: developmental delay (97%), hypotonia (93%), hypermobile joints (58%), CC hypoplasia/agenesis (56%), epilepsy (38%), macrocephaly (38%). Macrocephaly and epilepsy were mutually exclusive. Intellectual disability ranged from mild to severe, based on functional effects of each variant.

Functional evidence: HEK293T cells transfected with PPP2R1A mutants - variants from patients with less severe ID, no seizures, and sometimes macrocephaly typically showed normal B55α and STRN3 binding, while more severe ID, seizures, and sometimes microcephaly correlated with lost B55α binding and increased STRN3 binding.

22/33 (67%) of patients with PPP2R1A-Related Neurodevelopmental Disorder presented with corpus callosum hypo-/aplasia according to GeneReviews

PPP2R1A is now associated with AD Houge-Janssens syndrome 2, OMIM:616362 (OMIM accessed 13th Mar 2026). PPP2R1A is Definitve in ClinGen for an AD complex neurodevelopmental disorder (Nov 2022).
Sources: Literature; to: PMID: 33106617 Lenaerts et al., 2021
Report of 30 individuals with 16 different de novo variants in PPP2R1A. Shared phenotype: developmental delay (97%), hypotonia (93%), hypermobile joints (58%), CC hypoplasia/agenesis (56%), epilepsy (38%), macrocephaly (38%). Macrocephaly and epilepsy were mutually exclusive. Intellectual disability ranged from mild to severe, based on functional effects of each variant.

Functional evidence: HEK293T cells transfected with PPP2R1A mutants - variants from patients with less severe ID, no seizures, and sometimes macrocephaly typically showed normal B55α and STRN3 binding, while more severe ID, seizures, and sometimes microcephaly correlated with lost B55α binding and increased STRN3 binding.

22/33 (67%) of patients with PPP2R1A-Related Neurodevelopmental Disorder presented with corpus callosum hypo-/aplasia according to GeneReviews (https://www.ncbi.nlm.nih.gov/books/NBK580243/)

PPP2R1A is now associated with AD Houge-Janssens syndrome 2, OMIM:616362 (OMIM accessed 13th Mar 2026). PPP2R1A is Definitve in ClinGen for an AD complex neurodevelopmental disorder (Nov 2022).
Sources: Literature
Malformations of cortical development v7.38 PPP2R1A Ida Ertmanska changed review comment from: PMID: 33106617 Lenaerts et al., 2021
Report of 30 individuals with 16 different de novo variants in PPP2R1A. Shared phenotype: developmental delay (97%), hypotonia (93%), hypermobile joints (58%), CC hypoplasia/agenesis (56%), epilepsy (38%), macrocephaly (38%). Macrocephaly and epilepsy were mutually exclusive. Intellectual disability ranged from mild to severe, based on functional effects of each variant.

Functional evidence: HEK293T cells transfected with PPP2R1A mutants - variants from patients with less severe ID, no seizures, and sometimes macrocephaly typically showed normal B55α and STRN3 binding, while more severe ID, seizures, and sometimes microcephaly correlated with lost B55α binding and increased STRN3 binding.

PPP2R1A is now associated with AD Houge-Janssens syndrome 2, OMIM:616362 (OMIM accessed 13th Mar 2026). PPP2R1A is Definitve in ClinGen for an AD complex neurodevelopmental disorder (Nov 2022).
Sources: Literature; to: PMID: 33106617 Lenaerts et al., 2021
Report of 30 individuals with 16 different de novo variants in PPP2R1A. Shared phenotype: developmental delay (97%), hypotonia (93%), hypermobile joints (58%), CC hypoplasia/agenesis (56%), epilepsy (38%), macrocephaly (38%). Macrocephaly and epilepsy were mutually exclusive. Intellectual disability ranged from mild to severe, based on functional effects of each variant.

Functional evidence: HEK293T cells transfected with PPP2R1A mutants - variants from patients with less severe ID, no seizures, and sometimes macrocephaly typically showed normal B55α and STRN3 binding, while more severe ID, seizures, and sometimes microcephaly correlated with lost B55α binding and increased STRN3 binding.

22/33 (67%) of patients with PPP2R1A-Related Neurodevelopmental Disorder presented with corpus callosum hypo-/aplasia according to GeneReviews

PPP2R1A is now associated with AD Houge-Janssens syndrome 2, OMIM:616362 (OMIM accessed 13th Mar 2026). PPP2R1A is Definitve in ClinGen for an AD complex neurodevelopmental disorder (Nov 2022).
Sources: Literature
Malformations of cortical development v7.38 PPP2R1A Ida Ertmanska Classified gene: PPP2R1A as Amber List (moderate evidence)
Malformations of cortical development v7.38 PPP2R1A Ida Ertmanska Added comment: Comment on list classification: Comment on list classification: There are numerous individuals reported in literature with heterozygous PPP2R1A variants and a neurodevelopmental syndrome, which includes brain malformations (corpus callosum agenesis/hypoplasia, ventriculomegaly, and/or periventricular leukomalacia) in 40-67% of patients. Hence, this gene should be promoted to Green for Malformations of cortical development at the next update.
Malformations of cortical development v7.38 PPP2R1A Ida Ertmanska Gene: ppp2r1a has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v8.147 PPP2R1A Ida Ertmanska changed review comment from: PMID: 33106617 Lenaerts et al., 2021
Report of 30 individuals with 16 different de novo variants in PPP2R1A. Shared phenotype: developmental delay (97%), hypotonia (93%), hypermobile joints (58%), CC hypoplasia/agenesis (56%), epilepsy (38%), macrocephaly (38%). Macrocephaly and epilepsy were mutually exclusive. Intellectual disability ranged from mild to severe, based on functional effects of each variant.

Functional evidence: HEK293T cells transfected with PPP2R1A mutants - variants from patients with less severe ID, no seizures, and sometimes macrocephaly typically showed normal B55α and STRN3 binding, while more severe ID, seizures, and sometimes microcephaly correlated with lost B55α binding and increased STRN3 binding.

PPP2R1A is now associated with AD Houge-Janssens syndrome 2, OMIM:616362 (OMIM accessed 13th Mar 2026). PPP2R1A is Definitve in ClinGen for an AD complex neurodevelopmental disorder (Nov 2022).
Sources: Literature; to: PMID: 33106617 Lenaerts et al., 2021
Report of 30 individuals with 16 different de novo variants in PPP2R1A. Shared phenotype: developmental delay (97%), hypotonia (93%), hypermobile joints (58%), CC hypoplasia/agenesis (56%), epilepsy (38%), macrocephaly (38%). Macrocephaly and epilepsy were mutually exclusive. Intellectual disability ranged from mild to severe, based on functional effects of each variant.

Functional evidence: HEK293T cells transfected with PPP2R1A mutants - variants from patients with less severe ID, no seizures, and sometimes macrocephaly typically showed normal B55α and STRN3 binding, while more severe ID, seizures, and sometimes microcephaly correlated with lost B55α binding and increased STRN3 binding.

17/35 (49%) of patients with PPP2R1A-Related Neurodevelopmental Disorder presented with epilepsy according to GeneReviews (https://www.ncbi.nlm.nih.gov/books/NBK580243/)

PPP2R1A is now associated with AD Houge-Janssens syndrome 2, OMIM:616362 (OMIM accessed 13th Mar 2026). PPP2R1A is Definitve in ClinGen for an AD complex neurodevelopmental disorder (Nov 2022).
Sources: Literature
Intellectual disability v9.304 PPP2R1A Ida Ertmanska changed review comment from: PMID: 33106617 Lenaerts et al., 2021
Report of 30 individuals with 16 different de novo variants in PPP2R1A. Shared phenotype: developmental delay (97%), hypotonia (93%), hypermobile joints (58%), CC hypoplasia/agenesis (56%), epilepsy (38%), macrocephaly (38%). Macrocephaly and epilepsy were mutually exclusive. Intellectual disability ranged from mild to severe, based on functional effects of each variant.

Functional evidence: HEK293T cells transfected with PPP2R1A mutants - variants from patients with less severe ID, no seizures, and sometimes macrocephaly typically showed normal B55α and STRN3 binding, while more severe ID, seizures, and sometimes microcephaly correlated with lost B55α binding and increased STRN3 binding.

PPP2R1A is now associated with AD Houge-Janssens syndrome 2, OMIM:616362 (OMIM accessed 13th Mar 2026). PPP2R1A is Definitve in ClinGen for an AD complex neurodevelopmental disorder (Nov 2022).; to: PMID: 33106617 Lenaerts et al., 2021
Report of 30 individuals with 16 different de novo variants in PPP2R1A. Shared phenotype: developmental delay (97%), hypotonia (93%), hypermobile joints (58%), CC hypoplasia/agenesis (56%), epilepsy (38%), macrocephaly (38%). Macrocephaly and epilepsy were mutually exclusive. Intellectual disability ranged from mild to severe, based on functional effects of each variant.

Functional evidence: HEK293T cells transfected with PPP2R1A mutants - variants from patients with less severe ID, no seizures, and sometimes macrocephaly typically showed normal B55α and STRN3 binding, while more severe ID, seizures, and sometimes microcephaly correlated with lost B55α binding and increased STRN3 binding.

PPP2R1A is now associated with AD Houge-Janssens syndrome 2, OMIM:616362 (OMIM accessed 13th Mar 2026). PPP2R1A is Definitve in ClinGen for an AD complex neurodevelopmental disorder (Nov 2022).
Early onset or syndromic epilepsy v8.147 PPP2R1A Ida Ertmanska Classified gene: PPP2R1A as Amber List (moderate evidence)
Early onset or syndromic epilepsy v8.147 PPP2R1A Ida Ertmanska Added comment: Comment on list classification: There are numerous individuals reported in literature with heterozygous PPP2R1A variants and a neurodevelopmental syndrome, which includes epilepsy in 40-50% of patients. Hence, this gene should be promoted to Green for Early onset or syndromic epilepsy at the next update.
Early onset or syndromic epilepsy v8.147 PPP2R1A Ida Ertmanska Gene: ppp2r1a has been classified as Amber List (Moderate Evidence).
Malformations of cortical development v7.37 PPP2R1A Ida Ertmanska gene: PPP2R1A was added
gene: PPP2R1A was added to Malformations of cortical development. Sources: Literature
Q1_26_promote_green tags were added to gene: PPP2R1A.
Mode of inheritance for gene: PPP2R1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP2R1A were set to 33106617
Phenotypes for gene: PPP2R1A were set to Houge-Janssens syndrome 2, OMIM:616362; Houge-Janssens syndrome 2, MONDO:0014605
Review for gene: PPP2R1A was set to GREEN
Added comment: PMID: 33106617 Lenaerts et al., 2021
Report of 30 individuals with 16 different de novo variants in PPP2R1A. Shared phenotype: developmental delay (97%), hypotonia (93%), hypermobile joints (58%), CC hypoplasia/agenesis (56%), epilepsy (38%), macrocephaly (38%). Macrocephaly and epilepsy were mutually exclusive. Intellectual disability ranged from mild to severe, based on functional effects of each variant.

Functional evidence: HEK293T cells transfected with PPP2R1A mutants - variants from patients with less severe ID, no seizures, and sometimes macrocephaly typically showed normal B55α and STRN3 binding, while more severe ID, seizures, and sometimes microcephaly correlated with lost B55α binding and increased STRN3 binding.

PPP2R1A is now associated with AD Houge-Janssens syndrome 2, OMIM:616362 (OMIM accessed 13th Mar 2026). PPP2R1A is Definitve in ClinGen for an AD complex neurodevelopmental disorder (Nov 2022).
Sources: Literature
Early onset or syndromic epilepsy v8.146 PPP2R1A Ida Ertmanska gene: PPP2R1A was added
gene: PPP2R1A was added to Early onset or syndromic epilepsy. Sources: Literature
Q1_26_promote_green tags were added to gene: PPP2R1A.
Mode of inheritance for gene: PPP2R1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPP2R1A were set to 33106617
Phenotypes for gene: PPP2R1A were set to Houge-Janssens syndrome 2, OMIM:616362; Houge-Janssens syndrome 2, MONDO:0014605
Review for gene: PPP2R1A was set to GREEN
Added comment: PMID: 33106617 Lenaerts et al., 2021
Report of 30 individuals with 16 different de novo variants in PPP2R1A. Shared phenotype: developmental delay (97%), hypotonia (93%), hypermobile joints (58%), CC hypoplasia/agenesis (56%), epilepsy (38%), macrocephaly (38%). Macrocephaly and epilepsy were mutually exclusive. Intellectual disability ranged from mild to severe, based on functional effects of each variant.

Functional evidence: HEK293T cells transfected with PPP2R1A mutants - variants from patients with less severe ID, no seizures, and sometimes macrocephaly typically showed normal B55α and STRN3 binding, while more severe ID, seizures, and sometimes microcephaly correlated with lost B55α binding and increased STRN3 binding.

PPP2R1A is now associated with AD Houge-Janssens syndrome 2, OMIM:616362 (OMIM accessed 13th Mar 2026). PPP2R1A is Definitve in ClinGen for an AD complex neurodevelopmental disorder (Nov 2022).
Sources: Literature
Intellectual disability v9.304 PPP2R1A Ida Ertmanska Phenotypes for gene: PPP2R1A were changed from INTELLECTUAL DISABILITY to Houge-Janssens syndrome 2, OMIM:616362; Houge-Janssens syndrome 2, MONDO:0014605
Intellectual disability v9.304 PPP2R1A Ida Ertmanska Publications for gene: PPP2R1A were set to 25533962
Intellectual disability v9.303 PPP2R1A Ida Ertmanska edited their review of gene: PPP2R1A: Changed phenotypes to: Houge-Janssens syndrome 2, OMIM:616362, Houge-Janssens syndrome 2, MONDO:0014605
Intellectual disability v9.303 PPP2R1A Ida Ertmanska reviewed gene: PPP2R1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 33106617; Phenotypes: Houge-Janssens syndrome 2, OMIM:616362; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Skeletal dysplasia v8.38 DDR2 Eleanor Williams 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; Warburg-Cinotti syndrome, OMIM: 618175 to Spondylometaepiphyseal dysplasia, short limb-hand type 271665, at least 3 cases reported; Spondylometaepiphyseal dysplasia, short limb-hand type 271665
Structural eye disease v4.40 TOMM7 Eleanor Williams edited their review of gene: TOMM7: Added comment: This gene is linked to the syndromic mitochondrial condition Garg-Mishra progeroid syndrome OMIM:620601. The main phenotypes of this condition are severe postnatal growth failure / short stature, often with microcephaly and skeletal dysplasia, developmental delay and hypotonia. Moyamoya disease (cerebrovascular disorder) or a Leigh(-like) syndrome is also seen in some cases.

A subset of patients have an eye phenotype including 10 patients of Chinese/Taiwanese ancestry (all with p.P29L) and 1 patient of Indian ancestry (splice variant). The possibility of a founder effect has been explored but additional evidence comes from functional studies showing that the p.P29L variant affects mitochondrial function and thorough examination of the haplotype block for other candidate variants in Garg et al.

PMID: 36282599 Garg et al 2022 - 21-year-old man of Chinese ancestry with short stature, relative macrocephaly, facial dysmorphia, partial lipodystrophy, pendular nystagmus and high hyperopia with visual acuity of 3/60 in both eyes . He also had bilateral micro-ophthalmia with axial lengths of only 16.8 mm.
Through WES a variant was identified in TOMM7 (NC_000007.13:g.22862313G>A; NM_019059.4:c.86C>T; NP_061932.1:p.Pro29Leu) in the proband, and both the parents and the 2 unaffected siblings were heterozygous for the variant. Heterozygotes of this variant have been seen only in Koreans, Japanese, and other East Asians with a MAF of 0.000048 (gnomAD, v2.1.1).
The parents were found to be more distantly related than third-degree relatives. A 1.0 MB region of homozygosity that included TOMM7 on chromosome 7 was present in the proband, but not in any other family member. WGS)of the proband’s DNA did not identify any copy number variants or rare intronic variants in the regions of homozygosity across the proband’s genome. Functional studies identified that this is an inactivating variant associated with increased mitochondrial oxygen consumption.

PMID: 39615461 Li et al 2024 - 9 patients from 7 unrelated Taiwanese families with microcephaly, short stature, facial dysmorphia, developmental delay, atrophic macular scarring, and moyamoya disease that are homozygous for the TOMM7 p.P29L variant identified in the Garg et al publication. Hyperopia was seen in 4/7 familes, Maculopathy in 5 families, Nystagmus in 3 families, Strabismus in 4 families, Amblyobia in 5 families, and optic atrophy in 2 families. The probands showed higher levels of homozygosity compared to controls. The authors suggest a founder effect due to the high allele frequency of the variant in the Taiwanese population.
However, functional and knock out studies suggest that this is the causative variant. Deletion of tomm7 in zebrafish caused craniofacial and cerebrovascular defects that recapitulated human phenotypes. iPSC-derived endothelial cells with homozygous TOMM7 p.P29L showed increased TOM7 stability, enlarged mitochondria, increased senescence, and defective tube formation.

PMID: 39333057 Yeole et al 2025 - 4-month-old female child of Indian ethnicity significantly affected with neonatal-onset hypotonia, lactic acidosis, optic atrophy with absent foveal reflex, and neuroimaging findings suggestive of Leigh disease with a homozygous novel canonical splice variant, c.153-2A > C in TOMM7 (NM_019059.5). The variant leads to abnormal transcripts. Parents were heterozygous. An additional homozygous variant in CASR linked to hyperparathyroidism, neonatal severe (MIM# 239200) was identified. The proband died at 4.5 months.; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v9.303 CDC42BPB Ida Ertmanska changed review comment from: Comment on list classification: There are several individuals reported in literature with a neurodevelopmental syndrome. In a 2020 report of 14 patients, 12 individuals had syndromic DD and/or ID (PMID: 32031333). Since the initial report, several studies have linked the gene to a neurodevelopmental disorder, though clinical details are limited. Based on available evidence, this gene should be promoted to Green for Intellectual disability with MOI MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted.; to: Comment on list classification: There are several individuals reported in literature with a neurodevelopmental syndrome. In a 2020 report of 14 patients, 12 individuals had syndromic DD and/or ID (PMID: 32031333). Since the initial report, several studies have linked the gene to a neurodevelopmental disorder and ASD, though clinical details are limited. Based on available evidence, this gene should be promoted to Green for Intellectual disability with MOI MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted.
Intellectual disability v9.303 CDC42BPB Ida Ertmanska edited their review of gene: CDC42BPB: Changed publications to: 28263302, 31785789, 35586607, 36344539
Intellectual disability v9.303 CDC42BPB Ida Ertmanska changed review comment from: Further reports (few clinical details):

PMID: 36344539, Al Kasbi et al., 2022
4 yo male with hypotonia, global developmental delays and seizures, who had two homozygous variants: homozygous frameshift p.Ala1314GlyfsTer35 in CDC42BPB and homozygous missense p.Phe1306Val in SCN10A.

PMID: 35586607 French et al., 2022
Trio WGS cohort. Case 190 (suppl data): heterozygous for c.2605dup, p.Gln869ProfsTer85, de novo; phenotype described as 'CDC42BPB-related disease'.

PMID: 31785789 Turner et al., 2019
Cohort of 8000+ parent-child trios with NDDs. Cases from suppl data table S2, all variants are de novo:
NDAR_INVAZ651VGG_wes1 - patient with autism, het for CDC42BPB:c.4951G>A, p.Val1651Met - 18 alleles reported in gnomAD v4.1.0
13934.p1 - patient with autism, het for CDC42BPB:c.4805A>G, p.Gln1602Arg - not in gnomAD v4.1.0
13606.p1 - patient with autism, het for CDC42BPB:c.2290C>T, p.Arg764* - 2 alleles in gnomAD v4.1.0
14338.p1 - patient with autism, het for CDC42BPB:c.1891_1893dup, p.Ala631dup - not in gnomAD v4.1.0
DDD4K.04028 - patient with a developmental disorder, het for CDC42BPB:c.3349G>A, p.Ala1117Thr - 32 alleles in gnomAD v4.1.0
DDD4K.02790 - patient with a developmental disorder, het for CDC42BPB:c.1067dup, p.Tyr357Leufs*4 - not in gnomAD v4.1.0

PMID: 28263302 Yuen et al., 2017
Reported a de novo frameshift deletion in exon 11 of the CDC42BPB gene (Chr14:103442072_103442075delCTTT) in an individual with autism spectrum disorder by trio genome sequencing (sample AU079605; Supplementary Table 4).; to: Further reports (few clinical details):

PMID: 36344539, Al Kasbi et al., 2022
4 yo male with hypotonia, global developmental delays and seizures, who had two homozygous variants: homozygous frameshift p.Ala1314GlyfsTer35 in CDC42BPB and homozygous missense p.Phe1306Val in SCN10A.

PMID: 35586607 French et al., 2022
Trio WGS cohort. Case 190 (suppl data): heterozygous for c.2605dup, p.Gln869ProfsTer85, de novo; phenotype described as 'CDC42BPB-related disease'.

PMID: 31785789 Turner et al., 2019
Cohort of 8000+ parent-child trios with NDDs. Cases from suppl data table S2, all variants are de novo:
NDAR_INVAZ651VGG_wes1 - patient with autism, het for CDC42BPB:c.4951G>A, p.Val1651Met - 18 alleles reported in gnomAD v4.1.0
13934.p1 - patient with autism, het for CDC42BPB:c.4805A>G, p.Gln1602Arg - not in gnomAD v4.1.0
13606.p1 - patient with autism, het for CDC42BPB:c.2290C>T, p.Arg764* - 2 alleles in gnomAD v4.1.0
14338.p1 - patient with autism, het for CDC42BPB:c.1891_1893dup, p.Ala631dup - not in gnomAD v4.1.0
DDD4K.04028 - patient with a developmental disorder, het for CDC42BPB:c.3349G>A, p.Ala1117Thr - 32 alleles in gnomAD v4.1.0
DDD4K.02790 - patient with a developmental disorder, het for CDC42BPB:c.1067dup, p.Tyr357Leufs*4 - not in gnomAD v4.1.0

PMID: 28263302 Yuen et al., 2017
Reported a de novo frameshift deletion in exon 11 of the CDC42BPB gene (Chr14:103442072_103442075delCTTT) in an individual with autism spectrum disorder by trio genome sequencing (sample AU079605; Supplementary Table 4).

CDC42BPB is included in G2P with limited confidence (monoallelic CDC42BPB-related neurodevelopmental disorder). It is rated Green on Intellectual disability syndromic and non-syndromic panel in PA Australia.
Intellectual disability v9.303 CDC42BPB Ida Ertmanska changed review comment from: Further reports (few clinical details):
PMID: 35586607 French et al., 2022
Trio WGS cohort. Case 190 (suppl data): heterozygous for c.2605dup, p.Gln869ProfsTer85, de novo; phenotype described as 'CDC42BPB-related disease'.

PMID: 31785789 Turner et al., 2019
Cohort of 8000+ parent-child trios with NDDs. Cases from suppl data table S2, all variants are de novo:
NDAR_INVAZ651VGG_wes1 - patient with autism, het for CDC42BPB:c.4951G>A, p.Val1651Met - 18 alleles reported in gnomAD v4.1.0
13934.p1 - patient with autism, het for CDC42BPB:c.4805A>G, p.Gln1602Arg - not in gnomAD v4.1.0
13606.p1 - patient with autism, het for CDC42BPB:c.2290C>T, p.Arg764* - 2 alleles in gnomAD v4.1.0
14338.p1 - patient with autism, het for CDC42BPB:c.1891_1893dup, p.Ala631dup - not in gnomAD v4.1.0
DDD4K.04028 - patient with a developmental disorder, het for CDC42BPB:c.3349G>A, p.Ala1117Thr - 32 alleles in gnomAD v4.1.0
DDD4K.02790 - patient with a developmental disorder, het for CDC42BPB:c.1067dup, p.Tyr357Leufs*4 - not in gnomAD v4.1.0; to: Further reports (few clinical details):

PMID: 36344539, Al Kasbi et al., 2022
4 yo male with hypotonia, global developmental delays and seizures, who had two homozygous variants: homozygous frameshift p.Ala1314GlyfsTer35 in CDC42BPB and homozygous missense p.Phe1306Val in SCN10A.

PMID: 35586607 French et al., 2022
Trio WGS cohort. Case 190 (suppl data): heterozygous for c.2605dup, p.Gln869ProfsTer85, de novo; phenotype described as 'CDC42BPB-related disease'.

PMID: 31785789 Turner et al., 2019
Cohort of 8000+ parent-child trios with NDDs. Cases from suppl data table S2, all variants are de novo:
NDAR_INVAZ651VGG_wes1 - patient with autism, het for CDC42BPB:c.4951G>A, p.Val1651Met - 18 alleles reported in gnomAD v4.1.0
13934.p1 - patient with autism, het for CDC42BPB:c.4805A>G, p.Gln1602Arg - not in gnomAD v4.1.0
13606.p1 - patient with autism, het for CDC42BPB:c.2290C>T, p.Arg764* - 2 alleles in gnomAD v4.1.0
14338.p1 - patient with autism, het for CDC42BPB:c.1891_1893dup, p.Ala631dup - not in gnomAD v4.1.0
DDD4K.04028 - patient with a developmental disorder, het for CDC42BPB:c.3349G>A, p.Ala1117Thr - 32 alleles in gnomAD v4.1.0
DDD4K.02790 - patient with a developmental disorder, het for CDC42BPB:c.1067dup, p.Tyr357Leufs*4 - not in gnomAD v4.1.0

PMID: 28263302 Yuen et al., 2017
Reported a de novo frameshift deletion in exon 11 of the CDC42BPB gene (Chr14:103442072_103442075delCTTT) in an individual with autism spectrum disorder by trio genome sequencing (sample AU079605; Supplementary Table 4).
Intellectual disability v9.303 CDC42BPB Ida Ertmanska edited their review of gene: CDC42BPB: Added comment: Comment on list classification: There are several individuals reported in literature with a neurodevelopmental syndrome. In a 2020 report of 14 patients, 12 individuals had syndromic DD and/or ID (PMID: 32031333). Since the initial report, several studies have linked the gene to a neurodevelopmental disorder, though clinical details are limited. Based on available evidence, this gene should be promoted to Green for Intellectual disability with MOI MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted.; Changed rating: GREEN
Structural eye disease v4.40 ARR3 Eleanor Williams Tag x-linked-over-dominance tag was added to gene: ARR3.
Structural eye disease v4.40 TOMM7 Eleanor Williams Tag Q1_25_ promote_green was removed from gene: TOMM7.
Structural eye disease v4.40 NR6A1 Eleanor Williams Tag Q3_25_promote_green was removed from gene: NR6A1.
Tag Q3_25_NHS_review was removed from gene: NR6A1.
Structural eye disease v4.40 FOXE3 Eleanor Williams Tag Q3_25_MOI was removed from gene: FOXE3.
Tag Q3_25_NHS_review was removed from gene: FOXE3.
Structural eye disease v4.40 FOXD3 Eleanor Williams Tag Q3_25_expert_review was removed from gene: FOXD3.
Tag Q3_25_demote_red was removed from gene: FOXD3.
Structural eye disease v4.40 EFEMP1 Eleanor Williams Tag Q3_25_promote_green was removed from gene: EFEMP1.
Structural eye disease v4.40 ARR3 Eleanor Williams Tag Q2_25_ promote_green was removed from gene: ARR3.
Structural eye disease v4.40 ARR3 Eleanor Williams Added comment: Comment on mode of inheritance: Note: this gene is linked to a condition that presents in females only, although hemizygous variants in males may also be prioritised with this mode of inheritance.
Structural eye disease v4.40 ARR3 Eleanor Williams Mode of inheritance for gene: ARR3 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Structural eye disease v4.39 TOMM7 Eleanor Williams reviewed gene: TOMM7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Structural eye disease v4.39 NR6A1 Eleanor Williams reviewed gene: NR6A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Structural eye disease v4.39 FOXE3 Eleanor Williams commented on gene: FOXE3: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Structural eye disease v4.39 FOXD3 Eleanor Williams reviewed gene: FOXD3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Structural eye disease v4.39 EFEMP1 Eleanor Williams reviewed gene: EFEMP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Structural eye disease v4.39 ARR3 Eleanor Williams reviewed gene: ARR3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Structural eye disease v4.38 TOMM7 Eleanor Williams Source NHS GMS was added to TOMM7.
Source Expert Review Green was added to TOMM7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v4.38 NR6A1 Eleanor Williams Source NHS GMS was added to NR6A1.
Source Expert Review Green was added to NR6A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v4.38 FOXE3 Eleanor Williams Mode of inheritance for gene FOXE3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Structural eye disease v4.38 FOXD3 Eleanor Williams Source Expert Review Red was added to FOXD3.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Structural eye disease v4.38 EFEMP1 Eleanor Williams Source Expert Review Green was added to EFEMP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Structural eye disease v4.38 ARR3 Eleanor Williams Source NHS GMS was added to ARR3.
Source Expert Review Green was added to ARR3.
Mode of inheritance for gene ARR3 was changed from Other to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.303 XPA Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: XPA.
Intellectual disability v9.303 WDR47 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: WDR47.
Intellectual disability v9.303 WBP4 Arina Puzriakova Tag Q4_24_NHS_review was removed from gene: WBP4.
Tag Q4_24_promote_green was removed from gene: WBP4.
Intellectual disability v9.303 WARS Arina Puzriakova Tag Q3_25_promote_green was removed from gene: WARS.
Intellectual disability v9.303 VPS33A Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: VPS33A.
Intellectual disability v9.303 UPF1 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: UPF1.
Tag Q3_25_NHS_review was removed from gene: UPF1.
Intellectual disability v9.303 UNC13A Arina Puzriakova Tag Q3_25_promote_green was removed from gene: UNC13A.
Tag Q3_25_NHS_review was removed from gene: UNC13A.
Intellectual disability v9.303 POLRMT Achchuthan Shanmugasundram Added comment: Comment on phenotypes: OMIM phenotype was last accessed on 12 March 2026.
Intellectual disability v9.303 POLRMT Achchuthan Shanmugasundram Phenotypes for gene: POLRMT were changed from Combined oxidative phosphorylation deficiency 55, OMIM:619743 to Combined oxidative phosphorylation deficiency 55, OMIM:619743; combined oxidative phosphorylation deficiency 55, MONDO:0859228
Intellectual disability v9.302 UGGT1 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: UGGT1.
Tag Q3_25_NHS_review was removed from gene: UGGT1.
Intellectual disability v9.302 UBR5 Arina Puzriakova Tag dd_review was removed from gene: UBR5.
Tag Q3_25_promote_green was removed from gene: UBR5.
Intellectual disability v9.302 TUBGCP2 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: TUBGCP2.
Intellectual disability v9.302 POLRMT Achchuthan Shanmugasundram Publications for gene: POLRMT were set to 24386581; 33602924
Intellectual disability v9.301 TSPAN7 Arina Puzriakova Tag Q3_25_expert_review was removed from gene: TSPAN7.
Tag Q3_25_demote_amber was removed from gene: TSPAN7.
Intellectual disability v9.301 TNR Arina Puzriakova Tag Q3_25_promote_green was removed from gene: TNR.
Intellectual disability v9.301 POLRMT Achchuthan Shanmugasundram reviewed gene: POLRMT: Rating: GREEN; Mode of pathogenicity: None; Publications: 33602924, 40583167; Phenotypes: Combined oxidative phosphorylation deficiency 55, OMIM:619743, combined oxidative phosphorylation deficiency 55, MONDO:0859228; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v9.301 TFG Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: TFG.
Likely inborn error of metabolism v8.98 POLRMT Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v9.301 TARS2 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: TARS2.
Early onset or syndromic epilepsy v8.145 HCN2 Ida Ertmanska Phenotypes for gene: HCN2 were changed from Genetic epilepsy with febrile seizures plus; Other seizure disorders to Generalized epilepsy with febrile seizures plus, type 11, OMIM:602477; neurodevelopmental disorder, MONDO:0700092
Intellectual disability v9.301 TAOK2 Arina Puzriakova Tag Q1_25_ NHS_review was removed from gene: TAOK2.
Tag Q1_25_ promote_green was removed from gene: TAOK2.
Intellectual disability v9.301 SUPV3L1 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: SUPV3L1.
Likely inborn error of metabolism v8.98 POLRMT Achchuthan Shanmugasundram commented on gene: POLRMT: PMID:40583167 (2026) reported the identification of POLRMT variants in six new patients from six unrelated families. Five of these patients had biallelic variants and one patient had monoallelic POLRMT variant. The patients showed extended phenotypic abnormalities often presenting early in life with features including global developmental delay, cognitive impairment, short stature and muscular hypotonia.
Intellectual disability v9.301 SPOUT1 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: SPOUT1.
Early onset or syndromic epilepsy v8.144 HCN2 Ida Ertmanska Publications for gene: HCN2 were set to 29064616; 20437590; 12514127; 17931874; 22131395
Intellectual disability v9.301 SPAST Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: SPAST.
Intellectual disability v9.301 SOD1 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: SOD1.
Likely inborn error of metabolism v8.98 POLRMT Achchuthan Shanmugasundram commented on gene: POLRMT: The rating of this gene has been updated to green and the mode of inheritance set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Likely inborn error of metabolism v8.98 POLRMT Achchuthan Shanmugasundram Deleted their comment
Intellectual disability v9.301 SMARCA1 Arina Puzriakova Tag Q2_25_ promote_green was removed from gene: SMARCA1.
Intellectual disability v9.301 SLC5A7 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: SLC5A7.
Likely inborn error of metabolism v8.98 POLRMT Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There are nine unrelated families with biallelic POLRMT variants and three unrelated families with monoallelic variants reported in the literature. Hence, this gene can be rated green with 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' as MOI.
Likely inborn error of metabolism v8.98 POLRMT Achchuthan Shanmugasundram Mode of inheritance for gene: POLRMT was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v9.301 SF1 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: SF1.
Tag Q3_25_NHS_review was removed from gene: SF1.
Intellectual disability v9.301 SEL1L Arina Puzriakova Tag Q2_25_ promote_green was removed from gene: SEL1L.
Tag Q2_25_ NHS_review was removed from gene: SEL1L.
Intellectual disability v9.301 RSPRY1 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: RSPRY1.
Likely inborn error of metabolism v8.97 POLRMT Achchuthan Shanmugasundram Added comment: Comment on phenotypes: OMIM phenotype was last accessed on 12 March 2026.
Likely inborn error of metabolism v8.97 POLRMT Achchuthan Shanmugasundram Phenotypes for gene: POLRMT were changed from Combined oxidative phosphorylation deficiency 55, OMIM:619743 to Combined oxidative phosphorylation deficiency 55, OMIM:619743; combined oxidative phosphorylation deficiency 55, MONDO:0859228
Intellectual disability v9.301 RREB1 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: RREB1.
Tag Q3_25_NHS_review was removed from gene: RREB1.
Intellectual disability v9.301 RNU5B-1 Arina Puzriakova Tag dd_review was removed from gene: RNU5B-1.
Tag Q3_25_promote_green was removed from gene: RNU5B-1.
Mitochondrial disorders v9.46 POLRMT Achchuthan Shanmugasundram Publications for gene: POLRMT were set to 24386581; 33602924
Intellectual disability v9.301 RNU2-2P Arina Puzriakova Tag dd_review was removed from gene: RNU2-2P.
Tag Q2_25_ promote_green was removed from gene: RNU2-2P.
Possible mitochondrial disorder - nuclear genes v4.23 POLRMT Achchuthan Shanmugasundram changed review comment from: Comment on mode of inheritance: There are nine unrelated families with biallelic POLRMT variants and there unrelated families with monoallelic variants reported in the literature. Hence, this gene can be rated green with 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' MOI.; to: Comment on mode of inheritance: There are nine unrelated families with biallelic POLRMT variants and three unrelated families with monoallelic variants reported in the literature. Hence, this gene can be rated green with 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' as MOI.
Intellectual disability v9.301 PTRH2 Arina Puzriakova Tag watchlist was removed from gene: PTRH2.
Tag Q1_25_ promote_green was removed from gene: PTRH2.
Mitochondrial disorders v9.45 POLRMT Achchuthan Shanmugasundram changed review comment from: Comment on mode of inheritance: There are nine unrelated families with biallelic POLRMT variants and there unrelated families with monoallelic variants reported in the literature. Hence, this gene can be rated green with 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' MOI.; to: Comment on mode of inheritance: There are nine unrelated families with biallelic POLRMT variants and three unrelated families with monoallelic variants reported in the literature. Hence, this gene can be rated green with 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' as MOI.
Intellectual disability v9.301 PTBP1 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: PTBP1.
Intellectual disability v9.301 PPP2R5C Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: PPP2R5C.
Likely inborn error of metabolism v8.96 POLRMT Achchuthan Shanmugasundram Publications for gene: POLRMT were set to 24386581; 33602924
Intellectual disability v9.301 PPOX Arina Puzriakova Tag Q3_25_promote_green was removed from gene: PPOX.
Intellectual disability v9.301 PNPLA8 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: PNPLA8.
Intellectual disability v9.301 PABPC1 Arina Puzriakova Tag dd_review was removed from gene: PABPC1.
Tag Q4_24_MOI was removed from gene: PABPC1.
Likely inborn error of metabolism v8.95 POLRMT Achchuthan Shanmugasundram edited their review of gene: POLRMT: Added comment: PMID:40583167 (2026) reported the identification of POLRMT variants in six new patients from six unrelated families. Five of these patients had biallelic variants and one patient had monoallelic POLRMT variant. The patients showed extended phenotypic abnormalities often presenting early in life with features including global developmental delay, cognitive impairment, short stature and muscular hypotonia.; Changed publications to: 33602924, 40583167; Changed phenotypes to: Combined oxidative phosphorylation deficiency 55, OMIM:619743, combined oxidative phosphorylation deficiency 55, MONDO:0859228; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v9.301 OPA1 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: OPA1.
Intellectual disability v9.301 NOTCH3 Arina Puzriakova Tag dd_review was removed from gene: NOTCH3.
Tag Q3_25_promote_green was removed from gene: NOTCH3.
Childhood onset dystonia, chorea or related movement disorder v7.17 HCN2 Ida Ertmanska Classified gene: HCN2 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v7.17 HCN2 Ida Ertmanska Added comment: Comment on list classification: In a cohort of 21 patients with HCN2 variants (mono- and bi- allelic), 12 presented with movement disorders, including dystonia, tremor, cerebellar signs, and stereotypies. Hence, this gene should be promoted to Green on Childhood onset dystonia, chorea or related movement disorder with MOI BOTH monoallelic and biallelic, autosomal or pseudoautosomal.
Childhood onset dystonia, chorea or related movement disorder v7.17 HCN2 Ida Ertmanska Gene: hcn2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v9.301 NHLRC2 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: NHLRC2.
Intellectual disability v9.301 NAV3 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: NAV3.
Intellectual disability v9.301 NAA20 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: NAA20.
Intellectual disability v9.301 HCN2 Ida Ertmanska Classified gene: HCN2 as Amber List (moderate evidence)
Intellectual disability v9.301 HCN2 Ida Ertmanska Added comment: Comment on list classification: In a cohort of 21 patients with HCN2 variants (mono- and bi- allelic), 17 presented with syndromic ID/DD, often severe. Hence, this gene should be promoted to Green on Intellectual disability with MOI BOTH monoallelic and biallelic, autosomal or pseudoautosomal.
Intellectual disability v9.301 HCN2 Ida Ertmanska Gene: hcn2 has been classified as Amber List (Moderate Evidence).
Intellectual disability v9.300 MRPL49 Arina Puzriakova Tag Q2_25_ promote_green was removed from gene: MRPL49.
Intellectual disability v9.300 MED16 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: MED16.
Tag Q3_25_NHS_review was removed from gene: MED16.
Intellectual disability v9.300 MED12L Arina Puzriakova Tag Q3_25_promote_green was removed from gene: MED12L.
Mitochondrial disorders v9.45 POLRMT Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There are nine unrelated families with biallelic POLRMT variants and there unrelated families with monoallelic variants reported in the literature. Hence, this gene can be rated green with 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' MOI.
Mitochondrial disorders v9.45 POLRMT Achchuthan Shanmugasundram Mode of inheritance for gene: POLRMT was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v9.300 MAP4K4 Arina Puzriakova Tag Q2_25_ promote_green was removed from gene: MAP4K4.
Intellectual disability v9.300 MAG Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: MAG.
Intellectual disability v9.300 LAMC3 Arina Puzriakova Tag Q3_25_MOI was removed from gene: LAMC3.
Tag Q3_25_expert_review was removed from gene: LAMC3.
Tag Q3_25_demote_red was removed from gene: LAMC3.
Intellectual disability v9.300 KIRREL3 Arina Puzriakova Tag Q3_25_expert_review was removed from gene: KIRREL3.
Tag Q3_25_demote_red was removed from gene: KIRREL3.
Intellectual disability v9.300 KIAA0556 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: KIAA0556.
Intellectual disability v9.300 KDM5B Arina Puzriakova Tag Q2_25_ MOI was removed from gene: KDM5B.
Tag Q2_25_expert_review was removed from gene: KDM5B.
Tag Q2_25_ NHS_review was removed from gene: KDM5B.
Intellectual disability v9.300 INPP4A Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: INPP4A.
Intellectual disability v9.300 HNRNPC Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: HNRNPC.
Mitochondrial disorders v9.44 POLRMT Achchuthan Shanmugasundram Added comment: Comment on phenotypes: OMIM phenotype was last accessed on 12 March 2026.
Mitochondrial disorders v9.44 POLRMT Achchuthan Shanmugasundram Phenotypes for gene: POLRMT were changed from Combined oxidative phosphorylation deficiency 55, OMIM:619743 to Combined oxidative phosphorylation deficiency 55, OMIM:619743; combined oxidative phosphorylation deficiency 55, MONDO:0859228
Intellectual disability v9.300 GTF3C3 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: GTF3C3.
Intellectual disability v9.300 GPATCH11 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: GPATCH11.
Intellectual disability v9.300 FLVCR1 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: FLVCR1.
Mitochondrial disorders v9.43 POLRMT Achchuthan Shanmugasundram edited their review of gene: POLRMT: Added comment: PMID:40583167 (2026) reported the identification of POLRMT variants in six new patients from six unrelated families. Five of these patients had biallelic variants and one patient had monoallelic POLRMT variant. The patients showed extended phenotypic abnormalities often presenting early in life with features including global developmental delay, cognitive impairment, short stature and muscular hypotonia.; Changed publications to: 33602924, 40583167; Changed phenotypes to: Combined oxidative phosphorylation deficiency 55, OMIM:619743, combined oxidative phosphorylation deficiency 55, MONDO:0859228; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v9.300 FBXO22 Arina Puzriakova Tag Q2_25_ promote_green was removed from gene: FBXO22.
Tag Q2_25_ NHS_review was removed from gene: FBXO22.
Childhood onset dystonia, chorea or related movement disorder v7.16 HCN2 Ida Ertmanska gene: HCN2 was added
gene: HCN2 was added to Childhood onset dystonia, chorea or related movement disorder. Sources: Literature
Q1_26_promote_green tags were added to gene: HCN2.
Mode of inheritance for gene: HCN2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: HCN2 were set to 40468825
Phenotypes for gene: HCN2 were set to Generalized epilepsy with febrile seizures plus, type 11, OMIM:602477; neurodevelopmental disorder, MONDO:0700092
Review for gene: HCN2 was set to GREEN
Added comment: PMID: 40468825 Houdayer et al., 2025
21 individuals with HCN2 variants from 15 unrelated families - 13 monoallelic cases and 8 biallelic. The phenotypic spectrum included developmental delay/intellectual disability (DD/ID, 17/21), epilepsy (10/21), language disorders (16/21), movement disorders (12/21), and axial hypotonia (10/21).
Movement disorders included dystonia, tremor, cerebellar signs, stereotypies. Muscle tone abnormalities included axial hypotonia, hypertonia, pyramidal signs and spasticity. Biallelic LOF cases uniformly presented with severe intellectual disability, while monoallelic cases showed mild to moderate ID (IQ 40-60) with evidence of skill regression. Heterozygous GOF variants resulted in borderline ID and milder epilepsy phenotype.
Thirteen pathogenic HCN2 variants (12 new and 1 already described) were identified: 11 missense, 1 recurrent inframe deletion, and 1 frameshift.

Functional evidence: electrophysiology with Xenopus laevis oocytes and membrane trafficking investigated in HEK cells - p.(Arg324His) variant showed a strong increase of HCN2 conductance; p.(Ala363Val) and p.(Met374Leu) exhibited dominant negative effects. The p.(Leu377His), p.(Pro493Leu), and p.(Gly587Asp) variants rendered HCN2 electrophysiologically silent and impaired membrane trafficking. Structural 3D-analysis revealed that, except for p.(Arg324His), all variants altered HCN2 stability.

HCN2 is associated with several AD phenotypes in OMIM: Generalized epilepsy with febrile seizures plus, type 11 602477; Febrile seizures, familial, 2 602477; {Epilepsy, idiopathic generalized, susceptibility to, 17} 602477 - all same MIM number (accessed 12th Mar 2026). Not yet added to ClinGen or Gene2Phenotype.
Sources: Literature
Intellectual disability v9.300 HCN2 Ida Ertmanska gene: HCN2 was added
gene: HCN2 was added to Intellectual disability. Sources: Literature
Q1_26_promote_green tags were added to gene: HCN2.
Mode of inheritance for gene: HCN2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: HCN2 were set to 40468825
Phenotypes for gene: HCN2 were set to Generalized epilepsy with febrile seizures plus, type 11, OMIM:602477; neurodevelopmental disorder, MONDO:0700092
Review for gene: HCN2 was set to GREEN
Added comment: PMID: 40468825 Houdayer et al., 2025
21 individuals with HCN2 variants from 15 unrelated families - 13 monoallelic cases and 8 biallelic. The phenotypic spectrum included developmental delay/intellectual disability (DD/ID, 17/21), epilepsy (10/21), language disorders (16/21), movement disorders (12/21), and axial hypotonia (10/21).
Movement disorders included dystonia, tremor, cerebellar signs, stereotypies. Muscle tone abnormalities included axial hypotonia, hypertonia, pyramidal signs and spasticity. Biallelic LOF cases uniformly presented with severe intellectual disability, while monoallelic cases showed mild to moderate ID (IQ 40-60) with evidence of skill regression. Heterozygous GOF variants resulted in borderline ID and milder epilepsy phenotype.
Thirteen pathogenic HCN2 variants (12 new and 1 already described) were identified: 11 missense, 1 recurrent inframe deletion, and 1 frameshift.

Functional evidence: electrophysiology with Xenopus laevis oocytes and membrane trafficking investigated in HEK cells - p.(Arg324His) variant showed a strong increase of HCN2 conductance; p.(Ala363Val) and p.(Met374Leu) exhibited dominant negative effects. The p.(Leu377His), p.(Pro493Leu), and p.(Gly587Asp) variants rendered HCN2 electrophysiologically silent and impaired membrane trafficking. Structural 3D-analysis revealed that, except for p.(Arg324His), all variants altered HCN2 stability.

HCN2 is associated with several AD phenotypes in OMIM: Generalized epilepsy with febrile seizures plus, type 11 602477; Febrile seizures, familial, 2 602477; {Epilepsy, idiopathic generalized, susceptibility to, 17} 602477 - all same MIM number (accessed 12th Mar 2026). Not yet added to ClinGen or Gene2Phenotype.
Sources: Literature
Intellectual disability v9.299 EXOSC8 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: EXOSC8.
Intellectual disability v9.299 EPB41L3 Arina Puzriakova Tag Q2_25_ promote_green was removed from gene: EPB41L3.
Tag Q2_25_ NHS_review was removed from gene: EPB41L3.
Possible mitochondrial disorder - nuclear genes v4.23 POLRMT Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There are nine unrelated families with biallelic POLRMT variants and there unrelated families with monoallelic variants reported in the literature. Hence, this gene can be rated green with 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' MOI.
Possible mitochondrial disorder - nuclear genes v4.23 POLRMT Achchuthan Shanmugasundram Mode of inheritance for gene: POLRMT was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Intellectual disability v9.299 EMX2 Arina Puzriakova Tag Q3_25_expert_review was removed from gene: EMX2.
Tag Q3_25_NHS_review was removed from gene: EMX2.
Tag Q3_25_demote_amber was removed from gene: EMX2.
Intellectual disability v9.299 ELFN1 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: ELFN1.
Intellectual disability v9.299 EEFSEC Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: EEFSEC.
Possible mitochondrial disorder - nuclear genes v4.22 POLRMT Achchuthan Shanmugasundram Added comment: Comment on phenotypes: OMIM phenotype was last accessed on 12 March 2026.
Possible mitochondrial disorder - nuclear genes v4.22 POLRMT Achchuthan Shanmugasundram Phenotypes for gene: POLRMT were changed from Combined oxidative phosphorylation deficiency 55, OMIM:619743 to Combined oxidative phosphorylation deficiency 55, OMIM:619743; combined oxidative phosphorylation deficiency 55, MONDO:0859228
Possible mitochondrial disorder - nuclear genes v4.21 POLRMT Achchuthan Shanmugasundram Publications for gene: POLRMT were set to 24386581; 33602924
Possible mitochondrial disorder - nuclear genes v4.20 POLRMT Achchuthan Shanmugasundram edited their review of gene: POLRMT: Added comment: PMID:40583167 (2026) reported the identification of POLRMT variants in six new patients from six unrelated families. Five of these patients had biallelic variants and one patient had monoallelic POLRMT variant. The patients showed extended phenotypic abnormalities often presenting early in life with features including global developmental delay, cognitive impairment, short stature and muscular hypotonia.; Changed publications to: 33602924, 40583167; Changed phenotypes to: Combined oxidative phosphorylation deficiency 55, OMIM:619743, combined oxidative phosphorylation deficiency 55, MONDO:0859228; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v8.143 HCN2 Ida Ertmanska edited their review of gene: HCN2: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v8.143 HCN2 Ida Ertmanska Tag Q1_26_promote_green was removed from gene: HCN2.
Early onset or syndromic epilepsy v8.143 HCN2 Ida Ertmanska Tag Q1_26_promote_green tag was added to gene: HCN2.
Early onset or syndromic epilepsy v8.143 HCN2 Ida Ertmanska reviewed gene: HCN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 40468825; Phenotypes: Generalized epilepsy with febrile seizures plus, type 11, OMIM:602477, neurodevelopmental disorder, MONDO:0700092; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Likely inborn error of metabolism v8.95 IDH1 Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: All IDH1 variants reported to be associated with MIMs #614875, #614569 and #166000 are somatic mosaic.
Likely inborn error of metabolism v8.95 IDH1 Achchuthan Shanmugasundram Mode of inheritance for gene: IDH1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability v9.299 EEF1D Arina Puzriakova Tag Q2_25_ promote_green was removed from gene: EEF1D.
Tag Q2_25_ NHS_review was removed from gene: EEF1D.
Intellectual disability v9.299 DDX39B Arina Puzriakova Tag Q2_25_ promote_green was removed from gene: DDX39B.
Tag Q2_25_ NHS_review was removed from gene: DDX39B.
Intellectual disability v9.299 CRNKL1 Arina Puzriakova Tag dd_review was removed from gene: CRNKL1.
Tag Q3_25_promote_green was removed from gene: CRNKL1.
Intellectual disability v9.299 CELF4 Arina Puzriakova changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. Additional comments from reviewing GLHs: GnomAD data would make this difficult to classify variants. All ClinVar variants are VUS.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. Additional comments from reviewing GLHs: gnomAD data would make this difficult to classify variants. All ClinVar variants are VUS.
Intellectual disability v9.299 CELF4 Arina Puzriakova Tag dd_review was removed from gene: CELF4.
Tag Q2_25_ promote_green was removed from gene: CELF4.
Intellectual disability v9.299 CDK9 Arina Puzriakova Tag watchlist was removed from gene: CDK9.
Tag Q3_25_promote_green was removed from gene: CDK9.
Intellectual disability v9.299 CCT6A Arina Puzriakova Tag Q3_25_promote_green was removed from gene: CCT6A.
Intellectual disability v9.299 C12orf66 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: C12orf66.
Intellectual disability v9.299 ATM Arina Puzriakova Tag Q2_25_ demote_red was removed from gene: ATM.
Tag Q2_25_expert_review was removed from gene: ATM.
Intellectual disability v9.299 ASCC3 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: ASCC3.
Intellectual disability v9.299 AP1B1 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: AP1B1.
Childhood onset hereditary spastic paraplegia v8.35 SPTSSA Achchuthan Shanmugasundram Tag Q1_26_MOI tag was added to gene: SPTSSA.
Childhood onset hereditary spastic paraplegia v8.35 SPTSSA Achchuthan Shanmugasundram Added comment: Comment on mode of inheritance: There are three unrelated published patient cases and an additional patient suggested by an NHS colleague are available in support of the association of monoallelic Thr51Ile variant with Spastic paraplegia 90A, autosomal dominant (MIM #620416). However, there is only one patient reported with biallelic SPTSSA variant. There is also functional evidence available for the variant and homozygous mouse knock-out model available.

The MOI should be set to 'BIALLELIC, autosomal or pseudoautosomal' with the current evidence.
Childhood onset hereditary spastic paraplegia v8.35 SPTSSA Achchuthan Shanmugasundram Mode of inheritance for gene: SPTSSA was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v8.34 SPTSSA Achchuthan Shanmugasundram Publications for gene: SPTSSA were set to 26438849; 33662400; 36718090
Childhood onset hereditary spastic paraplegia v8.33 SPTSSA Achchuthan Shanmugasundram edited their review of gene: SPTSSA: Added comment: PMID:40533086 (2026) reported a 10-year-old female patient with the same recurrent heterozygous pathogenic variant in SPTSSA (p.Thr51Ile) identified via exome sequencing and presenting with global developmental delay, inability to walk, axial hypotonia, extremity spasticity, dystonia, distal renal tubular acidosis, recurrent urinary tract infections, nephrolithiasis, neurogenic bladder, and primary polydipsia.; Changed publications to: 26438849, 33662400, 36718090, 40533086; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v8.99 THRB Achchuthan Shanmugasundram changed review comment from: There are additional published evidence available in support of the association of monoallelic variants in THRB gene with macular dystrophy. Hence, this gene solidly fits with green rating.

PMID:40295579 (2025) reported the identification of 12 autosomal dominant macular dystrophy (ADMD) patients from three unrelated families with THRB variants (c.283 + 1G > A in two families and c.283G > A in one family). Splicing assays showed complete exon 5 skipping or a 6 bp deletion in both variants.

PMID:41153457 (2025) reported the identification of a heterozygous THRB variant (c.283+1G>A) in a female patient and her son with macular dystrophy.; to: There is additional published evidence available in support of the association of monoallelic variants in THRB gene with macular dystrophy. Hence, this gene solidly fits with green rating.

PMID:40295579 (2025) reported the identification of 12 autosomal dominant macular dystrophy (ADMD) patients from three unrelated families with THRB variants (c.283 + 1G > A in two families and c.283G > A in one family). Splicing assays showed complete exon 5 skipping or a 6 bp deletion in both variants.

PMID:41153457 (2025) reported the identification of a heterozygous THRB variant (c.283+1G>A) in a female patient and her son with macular dystrophy.
Retinal disorders v8.99 THRB Achchuthan Shanmugasundram Tag watchlist was removed from gene: THRB.
Retinal disorders v8.99 THRB Achchuthan Shanmugasundram Publications for gene: THRB were set to 37547476
Retinal disorders v8.98 THRB Achchuthan Shanmugasundram edited their review of gene: THRB: Added comment: There are additional published evidence available in support of the association of monoallelic variants in THRB gene with macular dystrophy. Hence, this gene solidly fits with green rating.

PMID:40295579 (2025) reported the identification of 12 autosomal dominant macular dystrophy (ADMD) patients from three unrelated families with THRB variants (c.283 + 1G > A in two families and c.283G > A in one family). Splicing assays showed complete exon 5 skipping or a 6 bp deletion in both variants.

PMID:41153457 (2025) reported the identification of a heterozygous THRB variant (c.283+1G>A) in a female patient and her son with macular dystrophy.; Changed publications to: 37547476, 40295579, 41153457
Intellectual disability v9.299 XPA Arina Puzriakova reviewed gene: XPA: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 WDR47 Arina Puzriakova reviewed gene: WDR47: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 WBP4 Arina Puzriakova reviewed gene: WBP4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 WARS Arina Puzriakova reviewed gene: WARS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 VPS33A Arina Puzriakova reviewed gene: VPS33A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 UPF1 Arina Puzriakova reviewed gene: UPF1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 UNC13A Arina Puzriakova reviewed gene: UNC13A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 UGGT1 Arina Puzriakova reviewed gene: UGGT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 UBR5 Arina Puzriakova reviewed gene: UBR5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 TUBGCP2 Arina Puzriakova commented on gene: TUBGCP2: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v9.299 TSPAN7 Arina Puzriakova reviewed gene: TSPAN7: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 TNR Arina Puzriakova commented on gene: TNR: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v9.299 TFG Arina Puzriakova reviewed gene: TFG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 TARS2 Arina Puzriakova reviewed gene: TARS2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 TAOK2 Arina Puzriakova reviewed gene: TAOK2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 SUPV3L1 Arina Puzriakova reviewed gene: SUPV3L1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 SPOUT1 Arina Puzriakova reviewed gene: SPOUT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 SPAST Arina Puzriakova edited their review of gene: SPAST: Added comment: The rating of this gene has been updated to green and the mode of inheritance updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v9.299 SOD1 Arina Puzriakova commented on gene: SOD1: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Intellectual disability v9.299 SMARCA1 Arina Puzriakova reviewed gene: SMARCA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 SLC5A7 Arina Puzriakova commented on gene: SLC5A7: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v9.299 SF1 Arina Puzriakova reviewed gene: SF1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 SEL1L Arina Puzriakova reviewed gene: SEL1L: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 RSPRY1 Arina Puzriakova commented on gene: RSPRY1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v9.299 RREB1 Arina Puzriakova reviewed gene: RREB1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 RNU5B-1 Arina Puzriakova commented on gene: RNU5B-1: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.
Intellectual disability v9.299 RNU2-2P Arina Puzriakova reviewed gene: RNU2-2P: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 PTRH2 Arina Puzriakova reviewed gene: PTRH2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 PTBP1 Arina Puzriakova commented on gene: PTBP1: 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.
Intellectual disability v9.299 PPP2R5C Arina Puzriakova reviewed gene: PPP2R5C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 PPP2R2B Arina Puzriakova edited their review of gene: PPP2R2B: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v9.299 PPOX Arina Puzriakova reviewed gene: PPOX: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 PNPLA8 Arina Puzriakova reviewed gene: PNPLA8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 PABPC1 Arina Puzriakova commented on gene: PABPC1
Intellectual disability v9.299 OPA1 Arina Puzriakova reviewed gene: OPA1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 NOTCH3 Arina Puzriakova reviewed gene: NOTCH3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 NHLRC2 Arina Puzriakova reviewed gene: NHLRC2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 NAV3 Arina Puzriakova reviewed gene: NAV3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 NAA20 Arina Puzriakova reviewed gene: NAA20: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 MRPL49 Arina Puzriakova reviewed gene: MRPL49: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 MED16 Arina Puzriakova reviewed gene: MED16: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 MED12L Arina Puzriakova reviewed gene: MED12L: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 MAP4K4 Arina Puzriakova edited their review of gene: MAP4K4: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v9.299 MAG Arina Puzriakova reviewed gene: MAG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 LAMC3 Arina Puzriakova reviewed gene: LAMC3: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 KIRREL3 Arina Puzriakova edited their review of gene: KIRREL3: Added comment: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.; Changed rating: RED
Intellectual disability v9.299 KIAA0556 Arina Puzriakova commented on gene: KIAA0556: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Intellectual disability v9.299 KDM5B Arina Puzriakova commented on gene: KDM5B: The mode of inheritance of this gene has been updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Intellectual disability v9.299 INPP4A Arina Puzriakova edited their review of gene: INPP4A: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v9.299 HNRNPC Arina Puzriakova reviewed gene: HNRNPC: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 GTF3C3 Arina Puzriakova commented on gene: GTF3C3: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v9.299 GPATCH11 Arina Puzriakova reviewed gene: GPATCH11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 FLVCR1 Arina Puzriakova reviewed gene: FLVCR1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 FBXO22 Arina Puzriakova reviewed gene: FBXO22: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 EXOSC8 Arina Puzriakova commented on gene: EXOSC8: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v9.299 EPB41L3 Arina Puzriakova commented on gene: EPB41L3: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v9.299 EMX2 Arina Puzriakova reviewed gene: EMX2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 ELFN1 Arina Puzriakova commented on gene: ELFN1: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Intellectual disability v9.299 EEFSEC Arina Puzriakova reviewed gene: EEFSEC: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 EEF1D Arina Puzriakova commented on gene: EEF1D: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v9.299 DDX39B Arina Puzriakova reviewed gene: DDX39B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 CRNKL1 Arina Puzriakova reviewed gene: CRNKL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 CELF4 Arina Puzriakova reviewed gene: CELF4: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 CDK9 Arina Puzriakova reviewed gene: CDK9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Intellectual disability v9.299 CCT6A Arina Puzriakova commented on gene: CCT6A: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.
Intellectual disability v9.299 C12orf66 Arina Puzriakova commented on gene: C12orf66: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Intellectual disability v9.299 ATM Arina Puzriakova edited their review of gene: ATM: Added comment: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.; Changed rating: RED
Intellectual disability v9.299 ASCC3 Arina Puzriakova edited their review of gene: ASCC3: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Intellectual disability v9.299 AP1B1 Arina Puzriakova reviewed gene: AP1B1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Monogenic diabetes v3.10 APPL1 Kevin Colclough reviewed gene: APPL1: Rating: RED; Mode of pathogenicity: None; Publications: PMID: 26073777, 40779032; Phenotypes: Diabetes; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Monogenic diabetes v3.10 SLC19A2 Kevin Colclough reviewed gene: SLC19A2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33571483, 39025920, 20301459, 10391221, 38932873; Phenotypes: Diabetes, megaloblastic anaemia, sensorineural hearing loss, optic atrophy; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Early onset or syndromic epilepsy v8.143 TANC2 Ida Ertmanska Classified gene: TANC2 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v8.143 TANC2 Ida Ertmanska Added comment: Comment on list classification: There are numerous patients reported in literature with heterozygous TANC2 variants and epilepsy. Epilepsy was the sole presenting feature in some cases. Hence, TANC2 should be promoted to Green at the next GMS update.
Early onset or syndromic epilepsy v8.143 TANC2 Ida Ertmanska Gene: tanc2 has been classified as Amber List (Moderate Evidence).
Monogenic diabetes v3.10 MAFA Kevin Colclough gene: MAFA was added
gene: MAFA was added to Monogenic diabetes. Sources: Expert Review
Mode of inheritance for gene: MAFA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAFA were set to PMID: 29339498; 34644565; 35406570; 17682063
Phenotypes for gene: MAFA were set to Diabetes; Insulinomatosis; Hyperinsulinaemic Hypoglycaemia
Penetrance for gene: MAFA were set to Incomplete
Review for gene: MAFA was set to GREEN
gene: MAFA was marked as current diagnostic
Added comment: Two large White European families with extensive family history of insulinomatosis and diabetes underwent whole exome sequencing (PMID: 29339498). The missense variant p.Ser64Phe in the MAFA gene co-segregated with both phenotypes in both families. A total of 17 individuals with diabetes and 10 individuals with insulinomatosis were heterozygous for the variant and there was almost complete penetrance for both phenotypes (90%). Most patients diagnosed with diabetes or impaired fasting glucose were males (male-to-female ratio was 3:1), and the mean age at diagnosis was 38.4 ± 16.5 y. They were not obese (mean BMI was 25). There were no other clinical features of insulin resistance, no history of diabetic ketoacidosis, and islet autoantibodies were negative, configuring a phenotype resembling maturity-onset diabetes of the young (MODY). Diabetes was managed with diet or oral medications (i.e., metformin and/or sulphonylureas) in most cases, with current HbA1c levels ranging between 37 and 74 mmol/mol (5.5–8.9%).

A third unrelated and unpublished individual referred to the Exeter Genomics Laboratory for MODY testing (diagnosed aged 28 years, slim, not insulin treated, parent with diabetes) was found to be heterozygous for MAFA p.Ser64Phe. The family also had an extensive family history of diabetes and hyperinsulinism in ten additional family members (5 with DM, 5 with HI). Five have been tested to date and all confirmed to be heterozygous for the variant (1 DM, 4 HI).

MAFA is a strong candidate gene as it plays a pivotal role in the regulation of insulin secretion in vivo. The β-cell–enriched MAFA transcription factor is required for postnatal function of murine β-cells, acting as transactivator of insulin and several genes involved with glucose-stimulated insulin secretion.

Functional analysis demonstrated that the p.Ser64Phe mutation significantly increased the stability of MAFA, whose levels were unaffected by variable glucose concentrations in β-cell lines, but also enhanced its transactivation activity (PMID: 29339498). The lack of up-regulation of MAFA in response to hyperglycaemia is expected to impair glucose-stimulated insulin secretion, and this mechanism presumably underlies the diabetes phenotype.

A heterozygous MAFA p.Ser64Phe mouse model has also been created. Males display impaired glucose tolerance, while females are slightly hypoglycaemic with improved blood glucose clearance (PMID: 34644565).

A second MAFA missense variant has also been published in a large with insulinomatosis and diabetes (PMID: 35406570). The p.Thr57Arg is located in in MAFA’s highly conserved transactivation domain. in vitro expression studies replacing Thr57 have been performed, demonstrating a phosphorylation defect with the impairment of transactivation activity and degradation (PMID: 17682063) Mild hyperglycaemia was observed in six additional, heterozygous family members.
Sources: Expert Review
Early onset or syndromic epilepsy v8.142 TANC2 Ida Ertmanska Tag Q1_26_promote_green tag was added to gene: TANC2.
Early onset or syndromic epilepsy v8.142 TANC2 Ida Ertmanska Publications for gene: TANC2 were set to 31616000
Early onset or syndromic epilepsy v8.141 TANC2 Ida Ertmanska Phenotypes for gene: TANC2 were changed from Intellectual developmental disorder with autistic features and language delay, with or without seizures, 618906 to Intellectual developmental disorder with autistic features and language delay, with or without seizures, OMIM:618906
Early onset or syndromic epilepsy v8.140 TANC2 Ida Ertmanska Mode of inheritance for gene: TANC2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v8.139 TANC2 Ida Ertmanska edited their review of gene: TANC2: Changed publications to: 34861844, 40110879
Early onset or syndromic epilepsy v8.139 TANC2 Ida Ertmanska changed review comment from: PMID: 34861844 - boy with Lennox-Gastaut syndrome (LGS), a severe epileptic encephalopathy.

TANC2 is linked to AD Intellectual developmental disorder with autistic features and language delay, with or without seizures, MIM:618906 (OMIM accessed 12th Mar 2026).; to: PMID: 40110879 Luo et al., 2025
Trio exome, Chinese cohort of epilepsy patients. De novo TANC2 variants were identified in six unrelated childhood-onset cases (4 null and 2 missense). Patients with null variants exhibited severe phenotypes: 3 with epilepsy and neurodevelopmental disorders, 1 individual with developmental and epileptic encephalopathy (DEE). In contrast, the patients with missense variants presented with only epilepsy.

PMID: 34861844 Tian et al., 2021
Case report of a Chinese boy (1yr 11 mo) with Lennox-Gastaut syndrome (LGS), a severe epileptic encephalopathy. WES + Sanger detected a de novo c.4321C > T(p.Gln1441Ter) mutation in TANC2.

TANC2 is linked to AD Intellectual developmental disorder with autistic features and language delay, with or without seizures, MIM:618906 (OMIM accessed 12th Mar 2026).
Monogenic diabetes v3.10 ZNF808 Kevin Colclough gene: ZNF808 was added
gene: ZNF808 was added to Monogenic diabetes. Sources: Expert Review
Mode of inheritance for gene: ZNF808 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNF808 were set to PMID: 41500078
Phenotypes for gene: ZNF808 were set to Diabetes
Penetrance for gene: ZNF808 were set to unknown
Review for gene: ZNF808 was set to GREEN
gene: ZNF808 was marked as current diagnostic
Added comment: Biallelic pathogenic protein-truncating/null variants in the ZNF808 gene cause permanent neonatal diabetes (De Franco et al 2023 PMID: 37973953) and the gene is included as a green gene on the R143 neonatal diabetes panel. More recently, the diabetes phenotype has been expanded to include transient neonatal diabetes and monogenic diabetes diagnosed in childhood and early adulthood with a MODY phenotype (Russ-Silsby et al 2026 PMID: 41500078). The paper reports three individuals with biallelic ZNF808 heterozygous loss of function variants diagnosed at ages 10, 14 and 23. All three individuals would meet current eligibility criteria for R141 testing and were in fact patients that previously had negative R141 testing and consented for further testing of ZNF808 on a research basis. Two of these patients were treated with an oral hyperglycaemic agent called a sulphonylurea and responded well to this treatment with good glycaemic control.
Sources: Expert Review
Early onset or syndromic epilepsy v8.139 TANC2 Ida Ertmanska edited their review of gene: TANC2: Changed publications to: 34861844; Changed phenotypes to: Intellectual developmental disorder with autistic features and language delay, with or without seizures, OMIM:618906
Early onset or syndromic epilepsy v8.139 TANC2 Ida Ertmanska changed review comment from: PMID: 34861844 - boy with Lennox-Gastaut syndrome (LGS), a severe epileptic encephalopathy.; to: PMID: 34861844 - boy with Lennox-Gastaut syndrome (LGS), a severe epileptic encephalopathy.

TANC2 is linked to AD Intellectual developmental disorder with autistic features and language delay, with or without seizures, MIM:618906 (OMIM accessed 12th Mar 2026).
Early onset or syndromic epilepsy v8.139 TANC2 Ida Ertmanska Deleted their comment
Early onset or syndromic epilepsy v8.139 TANC2 Ida Ertmanska commented on gene: TANC2: PMID: 34861844 - boy with Lennox-Gastaut syndrome (LGS), a severe epileptic encephalopathy.
Early onset or syndromic epilepsy v8.139 TANC2 Ida Ertmanska reviewed gene: TANC2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Likely inborn error of metabolism v8.94 UGGT1 Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: UGGT1.
Likely inborn error of metabolism v8.94 TRPM7 Achchuthan Shanmugasundram Tag Q1_25_ promote_green was removed from gene: TRPM7.
Likely inborn error of metabolism v8.94 TOMM7 Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: TOMM7.
Likely inborn error of metabolism v8.94 TEFM Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: TEFM.
Hereditary neuropathy or pain disorder v7.43 SOD1 Ida Ertmanska changed review comment from: Comment on list classification: There are more than 3 unrelated patients reported in literature with heterozygous SOD1 variants and hereditary neuropathy (motor and/ or sensory), often diagnosed as CMT disease. Sensory neuropathy may precede classical motor symptoms of ALS. Hence, SOD1 should be promoted to Green at the next GMS update.; to: Comment on list classification: There are more than 3 unrelated patients reported in literature with heterozygous SOD1 variants and hereditary neuropathy (motor and/ or sensory), often diagnosed as CMT disease. Sensory neuropathy may precede classical motor symptoms of ALS. Hence, SOD1 should be promoted to Green on Hereditary neuropathy or pain disorder at the next GMS update.
Hereditary neuropathy or pain disorder v7.43 SOD1 Ida Ertmanska changed review comment from: Comment on list classification: There are more than 3 unrelated patients reported in literature with heterozygous SOD1 variants and hereditary neuropathy (motor and/ or sensory). Sensory neuropathy may precede classical motor symptoms of ALS. Hence, SOD1 should be promoted to Green at the next GMS update.; to: Comment on list classification: There are more than 3 unrelated patients reported in literature with heterozygous SOD1 variants and hereditary neuropathy (motor and/ or sensory), often diagnosed as CMT disease. Sensory neuropathy may precede classical motor symptoms of ALS. Hence, SOD1 should be promoted to Green at the next GMS update.
Likely inborn error of metabolism v8.94 TAMM41 Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: TAMM41.
Hereditary neuropathy or pain disorder v7.43 SOD1 Ida Ertmanska Classified gene: SOD1 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v7.43 SOD1 Ida Ertmanska Added comment: Comment on list classification: There are more than 3 unrelated patients reported in literature with heterozygous SOD1 variants and hereditary neuropathy (motor and/ or sensory). Sensory neuropathy may precede classical motor symptoms of ALS. Hence, SOD1 should be promoted to Green at the next GMS update.
Hereditary neuropathy or pain disorder v7.43 SOD1 Ida Ertmanska Gene: sod1 has been classified as Amber List (Moderate Evidence).
Likely inborn error of metabolism v8.94 SUPV3L1 Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: SUPV3L1.
Likely inborn error of metabolism v8.94 SQOR Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: SQOR.
Hereditary neuropathy or pain disorder v7.42 SOD1 Ida Ertmanska gene: SOD1 was added
gene: SOD1 was added to Hereditary neuropathy or pain disorder. Sources: Literature
Q1_26_promote_green tags were added to gene: SOD1.
Mode of inheritance for gene: SOD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOD1 were set to 22475618; 36316849; 39932579
Phenotypes for gene: SOD1 were set to Charcot-Marie-Tooth disease, MONDO:0015626; Amyotrophic lateral sclerosis 1, OMIM:105400
Review for gene: SOD1 was set to GREEN
Added comment: PMID: 39932579 Ando et al., 2025
17 Japanese patients with 10 different missense SOD1 variants and peripheral neuropathy with avg onset at 47 years. Electrophysiology predominantly indicated a length-dependent, motor-dominant axonal neuropathy. Distal muscle weakness was noted in 9/13 patients, asymmetric muscle weakness and atrophy in 10/14, mild sensory disturbances observed in 8 patients, with some showing hyperreflexia and abnormal reflexes.

PMID: 36316849 Luo et al., 2022
Case report: 50yo female patient with hereditary motor and sensory neuropathy (CMT diagnosis). Presented with weakness of lower extremities. Heterozygous SOD1 c.140A>G, p(.His47Arg) was detected. Father with similar disease progression starting at age 50, not genotyped (deceased).

PMID: 22475618 Østern et al., 2012
Large Norwegian pedigree with hereditary neuropathy (diagnosis of CMT type 2), segregating with SOD1 c.140A>G, p.His47Arg variant.

PMID: 37610446 Bombaci et al., 2023 - literature review of ALS cases
Many authors reported an overlap of both sensory and motor symptoms in ALS patients. 20/29 ALS patients from case reports had sensory symptoms - common in spinal onset ALS. If sensory neuropathy precedes ALS there is usually a delay in ALS diagnosis.

SOD1 is linked to AD, AR Amyotrophic lateral sclerosis 1, OMIM:105400 & AR Spastic tetraplegia and axial hypotonia, progressive, OMIM:618598 (OMIM accessed 12th Mar 2026).
Sources: Literature
Likely inborn error of metabolism v8.94 SPATA5 Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: SPATA5.
Likely inborn error of metabolism v8.94 SLC25A36 Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: SLC25A36.
Likely inborn error of metabolism v8.94 SLC25A24 Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: SLC25A24.
Likely inborn error of metabolism v8.94 QARS Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: QARS.
Likely inborn error of metabolism v8.94 PPOX Achchuthan Shanmugasundram Tag Q3_25_MOI was removed from gene: PPOX.
DDG2P v6.426 KDM5B Achchuthan Shanmugasundram Added comment: Comment on phenotypes: Both monoallelic and biallelic variants in this gene have been associated with KDM5B-related neurodevelopmental disorder with Strong rating on the DD panel of Gene2Phenotype resource.

Biallelic KDM5B variants have been associated with relevant phenotype in OMIM (MIM #618109) and the record was accessed on 12 March 2026.
DDG2P v6.426 KDM5B Achchuthan Shanmugasundram Phenotypes for gene: KDM5B were changed from KDM5B-related neurodevelopmental disorder (biallelic); Intellectual developmental disorder, autosomal recessive 65, OMIM:618109; intellectual disability, autosomal recessive, MONDO:0020850; KDM5B-related neurodevelopmental disorder (monoallelic); neurodevelopmental disorder, MONDO:0700092 to KDM5B-related neurodevelopmental disorder (biallelic); Intellectual developmental disorder, autosomal recessive 65, OMIM:618109; intellectual disability, autosomal recessive, MONDO:0020850; KDM5B-related neurodevelopmental disorder (monoallelic); neurodevelopmental disorder, MONDO:0700092
DDG2P v6.425 KDM5B Achchuthan Shanmugasundram Added comment: Comment on phenotypes: Both monoallelic and biallelic variants in this gene have been associated with KDM5B-related neurodevelopmental disorder with Strong rating on the DD panel of Gene2Phenotype resource.

Biallelic KDM5B variants have been associated with relevant phenotype in OMIM (MIM #618109) and the record was accessed on 12 March 2026.
DDG2P v6.425 KDM5B Achchuthan Shanmugasundram Phenotypes for gene: KDM5B were changed from Autism to KDM5B-related neurodevelopmental disorder (biallelic); Intellectual developmental disorder, autosomal recessive 65, OMIM:618109; intellectual disability, autosomal recessive, MONDO:0020850; KDM5B-related neurodevelopmental disorder (monoallelic); neurodevelopmental disorder, MONDO:0700092
Intellectual disability v9.298 WDR47 Arina Puzriakova Source NHS GMS was added to WDR47.
Source Expert Review Green was added to WDR47.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 WBP4 Arina Puzriakova Source NHS GMS was added to WBP4.
Source Expert Review Green was added to WBP4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 WARS Arina Puzriakova Source NHS GMS was added to WARS.
Source Expert Review Green was added to WARS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 VPS33A Arina Puzriakova Source NHS GMS was added to VPS33A.
Source Expert Review Green was added to VPS33A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 UPF1 Arina Puzriakova Source NHS GMS was added to UPF1.
Source Expert Review Green was added to UPF1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 UNC13A Arina Puzriakova Source NHS GMS was added to UNC13A.
Source Expert Review Green was added to UNC13A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 UGGT1 Arina Puzriakova Source NHS GMS was added to UGGT1.
Source Expert Review Green was added to UGGT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 UBR5 Arina Puzriakova Source NHS GMS was added to UBR5.
Source Expert Review Green was added to UBR5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 TUBGCP2 Arina Puzriakova Source NHS GMS was added to TUBGCP2.
Source Expert Review Green was added to TUBGCP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 TSPAN7 Arina Puzriakova Source NHS GMS was added to TSPAN7.
Source Expert Review Amber was added to TSPAN7.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Intellectual disability v9.298 TNR Arina Puzriakova Source NHS GMS was added to TNR.
Source Expert Review Green was added to TNR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 TFG Arina Puzriakova Source NHS GMS was added to TFG.
Source Expert Review Green was added to TFG.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 TARS2 Arina Puzriakova Source NHS GMS was added to TARS2.
Source Expert Review Green was added to TARS2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 TAOK2 Arina Puzriakova Source NHS GMS was added to TAOK2.
Source Expert Review Green was added to TAOK2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 SUPV3L1 Arina Puzriakova Source NHS GMS was added to SUPV3L1.
Source Expert Review Green was added to SUPV3L1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 SPOUT1 Arina Puzriakova Source NHS GMS was added to SPOUT1.
Source Expert Review Green was added to SPOUT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 SPAST Arina Puzriakova Source NHS GMS was added to SPAST.
Source Expert Review Green was added to SPAST.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.94 POLRMT Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: POLRMT.
Intellectual disability v9.298 SOD1 Arina Puzriakova Source NHS GMS was added to SOD1.
Source Expert Review Green was added to SOD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 SMARCA1 Arina Puzriakova Source NHS GMS was added to SMARCA1.
Source Expert Review Green was added to SMARCA1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 SLC5A7 Arina Puzriakova Source NHS GMS was added to SLC5A7.
Source Expert Review Green was added to SLC5A7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 SF1 Arina Puzriakova Source NHS GMS was added to SF1.
Source Expert Review Green was added to SF1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 SEL1L Arina Puzriakova Source NHS GMS was added to SEL1L.
Source Expert Review Green was added to SEL1L.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 RSPRY1 Arina Puzriakova Source NHS GMS was added to RSPRY1.
Source Expert Review Green was added to RSPRY1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 RREB1 Arina Puzriakova Source NHS GMS was added to RREB1.
Source Expert Review Green was added to RREB1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 RNU5B-1 Arina Puzriakova Source NHS GMS was added to RNU5B-1.
Source Expert Review Green was added to RNU5B-1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 RNU2-2P Arina Puzriakova Source NHS GMS was added to RNU2-2P.
Source Expert Review Green was added to RNU2-2P.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 PTRH2 Arina Puzriakova Source NHS GMS was added to PTRH2.
Source Expert Review Green was added to PTRH2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 PTBP1 Arina Puzriakova Source Expert Review Green was added to PTBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 PPP2R5C Arina Puzriakova Source NHS GMS was added to PPP2R5C.
Source Expert Review Green was added to PPP2R5C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 PPP2R2B Arina Puzriakova Source NHS GMS was added to PPP2R2B.
Source Expert Review Green was added to PPP2R2B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 PPOX Arina Puzriakova Source NHS GMS was added to PPOX.
Source Expert Review Green was added to PPOX.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 PNPLA8 Arina Puzriakova Source NHS GMS was added to PNPLA8.
Source Expert Review Green was added to PNPLA8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 PABPC1 Arina Puzriakova Mode of inheritance for gene PABPC1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability v9.298 OPA1 Arina Puzriakova Source NHS GMS was added to OPA1.
Source Expert Review Green was added to OPA1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 NOTCH3 Arina Puzriakova Source NHS GMS was added to NOTCH3.
Source Expert Review Green was added to NOTCH3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 NHLRC2 Arina Puzriakova Source NHS GMS was added to NHLRC2.
Source Expert Review Green was added to NHLRC2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 NAV3 Arina Puzriakova Source NHS GMS was added to NAV3.
Source Expert Review Green was added to NAV3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 NAA20 Arina Puzriakova Source NHS GMS was added to NAA20.
Source Expert Review Green was added to NAA20.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 MRPL49 Arina Puzriakova Source NHS GMS was added to MRPL49.
Source Expert Review Green was added to MRPL49.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 MED16 Arina Puzriakova Source Expert Review Green was added to MED16.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 MED12L Arina Puzriakova Source NHS GMS was added to MED12L.
Source Expert Review Green was added to MED12L.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 MAP4K4 Arina Puzriakova Source NHS GMS was added to MAP4K4.
Source Expert Review Green was added to MAP4K4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 MAG Arina Puzriakova Source NHS GMS was added to MAG.
Source Expert Review Green was added to MAG.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 LAMC3 Arina Puzriakova Source NHS GMS was added to LAMC3.
Source Expert Review Red was added to LAMC3.
Mode of inheritance for gene LAMC3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Green List (high evidence) to Red List (low evidence)
Intellectual disability v9.298 KIRREL3 Arina Puzriakova Source Expert Review Red was added to KIRREL3.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Intellectual disability v9.298 KIAA0556 Arina Puzriakova Source NHS GMS was added to KIAA0556.
Source Expert Review Green was added to KIAA0556.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 KDM5B Arina Puzriakova Source NHS GMS was added to KDM5B.
Mode of inheritance for gene KDM5B was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Intellectual disability v9.298 INPP4A Arina Puzriakova Source NHS GMS was added to INPP4A.
Source Expert Review Green was added to INPP4A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 HNRNPC Arina Puzriakova Source NHS GMS was added to HNRNPC.
Source Expert Review Green was added to HNRNPC.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 GTF3C3 Arina Puzriakova Source NHS GMS was added to GTF3C3.
Source Expert Review Green was added to GTF3C3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 GPATCH11 Arina Puzriakova Source NHS GMS was added to GPATCH11.
Source Expert Review Green was added to GPATCH11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 FLVCR1 Arina Puzriakova Source NHS GMS was added to FLVCR1.
Source Expert Review Green was added to FLVCR1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 FBXO22 Arina Puzriakova Source NHS GMS was added to FBXO22.
Source Expert Review Green was added to FBXO22.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 EXOSC8 Arina Puzriakova Source NHS GMS was added to EXOSC8.
Source Expert Review Green was added to EXOSC8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 EPB41L3 Arina Puzriakova Source NHS GMS was added to EPB41L3.
Source Expert Review Green was added to EPB41L3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 EMX2 Arina Puzriakova Source NHS GMS was added to EMX2.
Source Expert Review Amber was added to EMX2.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Intellectual disability v9.298 ELFN1 Arina Puzriakova Source NHS GMS was added to ELFN1.
Source Expert Review Green was added to ELFN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 EEFSEC Arina Puzriakova Source NHS GMS was added to EEFSEC.
Source Expert Review Green was added to EEFSEC.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 EEF1D Arina Puzriakova Source NHS GMS was added to EEF1D.
Source Expert Review Green was added to EEF1D.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 DDX39B Arina Puzriakova Source NHS GMS was added to DDX39B.
Source Expert Review Green was added to DDX39B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 CRNKL1 Arina Puzriakova Source NHS GMS was added to CRNKL1.
Source Expert Review Green was added to CRNKL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 CDK9 Arina Puzriakova Source NHS GMS was added to CDK9.
Source Expert Review Green was added to CDK9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 CCT6A Arina Puzriakova Source NHS GMS was added to CCT6A.
Source Expert Review Green was added to CCT6A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 C12orf66 Arina Puzriakova Source NHS GMS was added to C12orf66.
Source Expert Review Green was added to C12orf66.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Intellectual disability v9.298 ATM Arina Puzriakova Source NHS GMS was added to ATM.
Source Expert Review Red was added to ATM.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Intellectual disability v9.298 ASCC3 Arina Puzriakova Source NHS GMS was added to ASCC3.
Source Expert Review Green was added to ASCC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
DDG2P v6.424 KDM5B Achchuthan Shanmugasundram edited their review of gene: KDM5B: Changed phenotypes to: KDM5B-related neurodevelopmental disorder (biallelic), Intellectual developmental disorder, autosomal recessive 65, OMIM:618109, intellectual disability, autosomal recessive, MONDO:0020850, KDM5B-related neurodevelopmental disorder (monoallelic), neurodevelopmental disorder, MONDO:0700092
Holoprosencephaly - NOT chromosomal v5.11 DISP1 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: DISP1.
Holoprosencephaly - NOT chromosomal v5.11 DISP1 Achchuthan Shanmugasundram reviewed gene: DISP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Holoprosencephaly - NOT chromosomal v5.10 DISP1 Arina Puzriakova Source Expert Review Green was added to DISP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.94 PITRM1 Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: PITRM1.
Likely inborn error of metabolism v8.94 PDE12 Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: PDE12.
Likely inborn error of metabolism v8.94 NDUFB7 Achchuthan Shanmugasundram Tag Q1_25_ promote_green was removed from gene: NDUFB7.
Likely inborn error of metabolism v8.94 MRPL49 Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: MRPL49.
Likely inborn error of metabolism v8.94 MRPL39 Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: MRPL39.
Likely inborn error of metabolism v8.94 MAN2B2 Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: MAN2B2.
Tag Q2_25_ NHS_review was removed from gene: MAN2B2.
Likely inborn error of metabolism v8.94 LIG3 Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: LIG3.
Likely inborn error of metabolism v8.94 KIAA0391 Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: KIAA0391.
Likely inborn error of metabolism v8.94 IDH3A Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: IDH3A.
Likely inborn error of metabolism v8.94 IDH1 Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: IDH1.
Hereditary neuropathy or pain disorder v7.41 TTC19 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: TTC19.
Tag Q3_25_NHS_review was removed from gene: TTC19.
Hereditary neuropathy or pain disorder v7.41 TDP1 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: TDP1.
Hereditary neuropathy or pain disorder v7.41 SPAST Arina Puzriakova Tag Q1_25_ MOI was removed from gene: SPAST.
Hereditary neuropathy or pain disorder v7.41 RCC1 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: RCC1.
Tag Q3_25_NHS_review was removed from gene: RCC1.
Likely inborn error of metabolism v8.94 HSD11B2 Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: HSD11B2.
Likely inborn error of metabolism v8.94 HPDL Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: HPDL.
Likely inborn error of metabolism v8.94 HMBS Achchuthan Shanmugasundram Tag Q2_25_ MOI was removed from gene: HMBS.
Likely inborn error of metabolism v8.94 GUK1 Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: GUK1.
Likely inborn error of metabolism v8.94 CYCS Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: CYCS.
Likely inborn error of metabolism v8.94 COX6A2 Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: COX6A2.
Likely inborn error of metabolism v8.94 COX4I1 Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: COX4I1.
Hereditary neuropathy or pain disorder v7.41 PIGG Arina Puzriakova Tag Q4_24_NHS_review was removed from gene: PIGG.
Tag Q4_24_promote_green was removed from gene: PIGG.
Likely inborn error of metabolism v8.94 COX18 Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: COX18.
Hereditary neuropathy or pain disorder v7.41 HMBS Arina Puzriakova Tag Q2_25_ MOI was removed from gene: HMBS.
Hereditary neuropathy or pain disorder v7.41 COX18 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: COX18.
Tag Q3_25_NHS_review was removed from gene: COX18.
Hereditary neuropathy or pain disorder v7.41 ARHGAP19 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: ARHGAP19.
Tag Q3_25_NHS_review was removed from gene: ARHGAP19.
Hereditary neuropathy or pain disorder v7.41 CPOX Arina Puzriakova Tag Q3_25_MOI was removed from gene: CPOX.
Tag Q3_25_expert_review was removed from gene: CPOX.
Likely inborn error of metabolism v8.94 COX11 Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: COX11.
Likely inborn error of metabolism v8.94 CMPK2 Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: CMPK2.
Likely inborn error of metabolism v8.94 C2orf69 Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: C2orf69.
Likely inborn error of metabolism v8.94 ACOX2 Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: ACOX2.
Likely inborn error of metabolism v8.94 CPOX Achchuthan Shanmugasundram Tag Q3_25_MOI was removed from gene: CPOX.
Tag Q3_25_expert_review was removed from gene: CPOX.
Likely inborn error of metabolism v8.94 UGGT1 Achchuthan Shanmugasundram commented on gene: UGGT1: 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.
Likely inborn error of metabolism v8.94 TRPM7 Achchuthan Shanmugasundram reviewed gene: TRPM7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Likely inborn error of metabolism v8.94 TOMM7 Achchuthan Shanmugasundram commented on gene: TOMM7: 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.
Likely inborn error of metabolism v8.94 TEFM Achchuthan Shanmugasundram commented on gene: TEFM: 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.
Likely inborn error of metabolism v8.94 TAMM41 Achchuthan Shanmugasundram commented on gene: TAMM41: 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.
Likely inborn error of metabolism v8.94 SUPV3L1 Achchuthan Shanmugasundram commented on gene: SUPV3L1: 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.
Likely inborn error of metabolism v8.94 SQOR Achchuthan Shanmugasundram commented on gene: SQOR: 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.
Likely inborn error of metabolism v8.94 SPATA5 Achchuthan Shanmugasundram commented on gene: SPATA5: 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.
Likely inborn error of metabolism v8.94 SLC25A36 Achchuthan Shanmugasundram commented on gene: SLC25A36: 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.
Likely inborn error of metabolism v8.94 SLC25A24 Achchuthan Shanmugasundram commented on gene: SLC25A24: 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.
Likely inborn error of metabolism v8.94 QARS Achchuthan Shanmugasundram commented on gene: QARS: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Likely inborn error of metabolism v8.94 PPOX Achchuthan Shanmugasundram commented on gene: PPOX: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Likely inborn error of metabolism v8.94 POLRMT Achchuthan Shanmugasundram commented on gene: POLRMT: The rating of this gene has been updated to green and the mode of inheritance set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Likely inborn error of metabolism v8.94 PITRM1 Achchuthan Shanmugasundram commented on gene: PITRM1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Likely inborn error of metabolism v8.94 PDE12 Achchuthan Shanmugasundram commented on gene: PDE12: 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.
Likely inborn error of metabolism v8.94 NDUFB7 Achchuthan Shanmugasundram reviewed gene: NDUFB7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Likely inborn error of metabolism v8.94 MRPL49 Achchuthan Shanmugasundram commented on gene: MRPL49: 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.
Likely inborn error of metabolism v8.94 MRPL39 Achchuthan Shanmugasundram commented on gene: MRPL39: 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.
Likely inborn error of metabolism v8.94 MAN2B2 Achchuthan Shanmugasundram edited their review of gene: MAN2B2: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Likely inborn error of metabolism v8.94 LIG3 Achchuthan Shanmugasundram commented on gene: LIG3: 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.
Likely inborn error of metabolism v8.94 KIAA0391 Achchuthan Shanmugasundram commented on gene: KIAA0391: 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.
Likely inborn error of metabolism v8.94 IDH3A Achchuthan Shanmugasundram commented on gene: IDH3A: 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.
Likely inborn error of metabolism v8.94 IDH1 Achchuthan Shanmugasundram reviewed gene: IDH1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Likely inborn error of metabolism v8.94 HSD11B2 Achchuthan Shanmugasundram commented on gene: HSD11B2: 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.
Likely inborn error of metabolism v8.94 HPDL Achchuthan Shanmugasundram commented on gene: HPDL: 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.
Likely inborn error of metabolism v8.94 HMBS Achchuthan Shanmugasundram commented on gene: HMBS
Likely inborn error of metabolism v8.94 GUK1 Achchuthan Shanmugasundram commented on gene: GUK1: 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.
Likely inborn error of metabolism v8.94 CYCS Achchuthan Shanmugasundram commented on gene: CYCS: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Likely inborn error of metabolism v8.94 CPOX Achchuthan Shanmugasundram commented on gene: CPOX
Likely inborn error of metabolism v8.94 COX6A2 Achchuthan Shanmugasundram commented on gene: COX6A2: 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.
Likely inborn error of metabolism v8.94 COX4I1 Achchuthan Shanmugasundram commented on gene: COX4I1: 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.
Likely inborn error of metabolism v8.94 COX18 Achchuthan Shanmugasundram commented on gene: COX18: 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.
Likely inborn error of metabolism v8.94 COX11 Achchuthan Shanmugasundram commented on gene: COX11: 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.
Likely inborn error of metabolism v8.94 CMPK2 Achchuthan Shanmugasundram commented on gene: CMPK2: 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.
Likely inborn error of metabolism v8.94 C2orf69 Achchuthan Shanmugasundram commented on gene: C2orf69: 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.
Likely inborn error of metabolism v8.94 ACOX2 Achchuthan Shanmugasundram reviewed gene: ACOX2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Likely inborn error of metabolism v8.93 UGGT1 Achchuthan Shanmugasundram Source NHS GMS was added to UGGT1.
Source Expert Review Green was added to UGGT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 TRPM7 Achchuthan Shanmugasundram Source NHS GMS was added to TRPM7.
Source Expert Review Green was added to TRPM7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 TOMM7 Achchuthan Shanmugasundram Source NHS GMS was added to TOMM7.
Source Expert Review Green was added to TOMM7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 TEFM Achchuthan Shanmugasundram Source Expert Review Green was added to TEFM.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 TAMM41 Achchuthan Shanmugasundram Source Expert Review Green was added to TAMM41.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 SUPV3L1 Achchuthan Shanmugasundram Source NHS GMS was added to SUPV3L1.
Source Expert Review Green was added to SUPV3L1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 SQOR Achchuthan Shanmugasundram Source NHS GMS was added to SQOR.
Source Expert Review Green was added to SQOR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 SPATA5 Achchuthan Shanmugasundram Source Expert Review Green was added to SPATA5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 SLC25A36 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC25A36.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 SLC25A24 Achchuthan Shanmugasundram Source Expert Review Green was added to SLC25A24.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 QARS Achchuthan Shanmugasundram Source NHS GMS was added to QARS.
Source Expert Review Green was added to QARS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 PPOX Achchuthan Shanmugasundram Mode of inheritance for gene PPOX was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Likely inborn error of metabolism v8.93 POLRMT Achchuthan Shanmugasundram Source Expert Review Green was added to POLRMT.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 PITRM1 Achchuthan Shanmugasundram Source NHS GMS was added to PITRM1.
Source Expert Review Green was added to PITRM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 PDE12 Achchuthan Shanmugasundram Source NHS GMS was added to PDE12.
Source Expert Review Green was added to PDE12.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 NDUFB7 Achchuthan Shanmugasundram Source NHS GMS was added to NDUFB7.
Source Expert Review Green was added to NDUFB7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 MRPL49 Achchuthan Shanmugasundram Source NHS GMS was added to MRPL49.
Source Expert Review Green was added to MRPL49.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 MRPL39 Achchuthan Shanmugasundram Source Expert Review Green was added to MRPL39.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 MAN2B2 Achchuthan Shanmugasundram Source NHS GMS was added to MAN2B2.
Source Expert Review Green was added to MAN2B2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 LIG3 Achchuthan Shanmugasundram Source Expert Review Green was added to LIG3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 KIAA0391 Achchuthan Shanmugasundram Source Expert Review Green was added to KIAA0391.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 IDH3A Achchuthan Shanmugasundram Source Expert Review Green was added to IDH3A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 IDH1 Achchuthan Shanmugasundram Source NHS GMS was added to IDH1.
Source Expert Review Green was added to IDH1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 HSD11B2 Achchuthan Shanmugasundram Source NHS GMS was added to HSD11B2.
Source Expert Review Green was added to HSD11B2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 HPDL Achchuthan Shanmugasundram Source Expert Review Green was added to HPDL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 HMBS Achchuthan Shanmugasundram Mode of inheritance for gene HMBS was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Likely inborn error of metabolism v8.93 GUK1 Achchuthan Shanmugasundram Source NHS GMS was added to GUK1.
Source Expert Review Green was added to GUK1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 CYCS Achchuthan Shanmugasundram Source NHS GMS was added to CYCS.
Source Expert Review Green was added to CYCS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 CPOX Achchuthan Shanmugasundram Mode of inheritance for gene CPOX was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism v8.93 COX6A2 Achchuthan Shanmugasundram Source Expert Review Green was added to COX6A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 COX4I1 Achchuthan Shanmugasundram Source NHS GMS was added to COX4I1.
Source Expert Review Green was added to COX4I1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 COX18 Achchuthan Shanmugasundram Source Expert Review Green was added to COX18.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 COX11 Achchuthan Shanmugasundram Source Expert Review Green was added to COX11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 CMPK2 Achchuthan Shanmugasundram Source NHS GMS was added to CMPK2.
Source Expert Review Green was added to CMPK2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 C2orf69 Achchuthan Shanmugasundram Source Expert Review Green was added to C2orf69.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Likely inborn error of metabolism v8.93 ACOX2 Achchuthan Shanmugasundram Source NHS GMS was added to ACOX2.
Source Expert Review Green was added to ACOX2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Unexplained young onset end-stage renal disease - additional genes v1.6 SIX5 Achchuthan Shanmugasundram Tag Q3_25_expert_review was removed from gene: SIX5.
Tag Q3_25_demote_red was removed from gene: SIX5.
Unexplained young onset end-stage renal disease - additional genes v1.6 SIX5 Achchuthan Shanmugasundram edited their review of gene: SIX5: Added comment: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.; Changed rating: RED
Unexplained young onset end-stage renal disease - additional genes v1.5 SIX5 Achchuthan Shanmugasundram Source Expert Review Red was added to SIX5.
Source NHS GMS was added to SIX5.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Hereditary neuropathy or pain disorder v7.41 TTC19 Achchuthan Shanmugasundram commented on gene: TTC19: 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.
Hereditary neuropathy or pain disorder v7.41 TDP1 Achchuthan Shanmugasundram commented on gene: TDP1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v7.41 SPAST Achchuthan Shanmugasundram commented on gene: SPAST
Hereditary neuropathy or pain disorder v7.41 RCC1 Achchuthan Shanmugasundram reviewed gene: RCC1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary neuropathy or pain disorder v7.41 PPOX Achchuthan Shanmugasundram commented on gene: PPOX: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v7.41 PIGG Achchuthan Shanmugasundram commented on gene: PIGG: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v7.41 HMBS Achchuthan Shanmugasundram commented on gene: HMBS: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Hereditary neuropathy or pain disorder v7.41 CPOX Achchuthan Shanmugasundram commented on gene: CPOX
Hereditary neuropathy or pain disorder v7.41 COX18 Achchuthan Shanmugasundram commented on gene: COX18: 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.
Hereditary neuropathy or pain disorder v7.41 ARHGAP19 Achchuthan Shanmugasundram commented on gene: ARHGAP19: 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.
Hereditary neuropathy or pain disorder v7.40 TTC19 Arina Puzriakova Source NHS GMS was added to TTC19.
Source Expert Review Green was added to TTC19.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v7.40 TDP1 Arina Puzriakova Source Expert Review Green was added to TDP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v7.40 SPAST Arina Puzriakova Mode of inheritance for gene SPAST was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v7.40 RCC1 Arina Puzriakova Source Expert Review Green was added to RCC1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v7.40 PPOX Arina Puzriakova Mode of inheritance for gene PPOX was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v7.40 PIGG Arina Puzriakova Source NHS GMS was added to PIGG.
Source Expert Review Green was added to PIGG.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v7.40 HMBS Arina Puzriakova Mode of inheritance for gene HMBS was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v7.40 CPOX Arina Puzriakova Mode of inheritance for gene CPOX was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v7.40 COX18 Arina Puzriakova Source NHS GMS was added to COX18.
Source Expert Review Green was added to COX18.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary neuropathy or pain disorder v7.40 ARHGAP19 Arina Puzriakova Source NHS GMS was added to ARHGAP19.
Source Expert Review Green was added to ARHGAP19.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v7.15 NOTCH3 Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: NOTCH3.
Tag Q3_25_NHS_review was removed from gene: NOTCH3.
White matter disorders and cerebral calcification - narrow panel v7.15 EPB41L3 Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: EPB41L3.
Tag Q2_25_ NHS_review was removed from gene: EPB41L3.
White matter disorders and cerebral calcification - narrow panel v7.15 CMPK2 Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: CMPK2.
White matter disorders and cerebral calcification - narrow panel v7.15 ATP11A Achchuthan Shanmugasundram Tag Q1_25_ promote_green was removed from gene: ATP11A.
White matter disorders and cerebral calcification - narrow panel v7.15 NOTCH3 Achchuthan Shanmugasundram commented on gene: NOTCH3: 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.
White matter disorders and cerebral calcification - narrow panel v7.15 EPB41L3 Achchuthan Shanmugasundram reviewed gene: EPB41L3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v7.15 CMPK2 Achchuthan Shanmugasundram reviewed gene: CMPK2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
White matter disorders and cerebral calcification - narrow panel v7.15 ATP11A Achchuthan Shanmugasundram reviewed gene: ATP11A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Haematological malignancies cancer susceptibility v4.40 SH2B3 Arina Puzriakova Tag Q2_25_ promote_green was removed from gene: SH2B3.
Haematological malignancies cancer susceptibility v4.40 DNAH9 Arina Puzriakova Tag Q2_25_ promote_green was removed from gene: DNAH9.
Haematological malignancies cancer susceptibility v4.40 DHX34 Arina Puzriakova Tag Q2_25_ promote_green was removed from gene: DHX34.
White matter disorders and cerebral calcification - narrow panel v7.14 NOTCH3 Achchuthan Shanmugasundram Source NHS GMS was added to NOTCH3.
Source Expert Review Green was added to NOTCH3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v7.14 EPB41L3 Achchuthan Shanmugasundram Source NHS GMS was added to EPB41L3.
Source Expert Review Green was added to EPB41L3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v7.14 CMPK2 Achchuthan Shanmugasundram Source NHS GMS was added to CMPK2.
Source Expert Review Green was added to CMPK2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
White matter disorders and cerebral calcification - narrow panel v7.14 ATP11A Achchuthan Shanmugasundram Source NHS GMS was added to ATP11A.
Source Expert Review Green was added to ATP11A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Haematological malignancies cancer susceptibility v4.40 TCF3 Arina Puzriakova Tag Q2_25_ promote_green was removed from gene: TCF3.
Tag Q2_25_expert_review was removed from gene: TCF3.
Haematological malignancies cancer susceptibility v4.40 POT1 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: POT1.
Tag Q3_25_expert_review was removed from gene: POT1.
Haematological malignancies cancer susceptibility v4.40 KDM1A Arina Puzriakova Tag Q3_25_promote_green was removed from gene: KDM1A.
Tag Q3_25_expert_review was removed from gene: KDM1A.
Haematological malignancies cancer susceptibility v4.40 HAVCR2 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: HAVCR2.
Tag Q3_25_expert_review was removed from gene: HAVCR2.
Haematological malignancies cancer susceptibility v4.40 TCF3 Arina Puzriakova edited their review of gene: TCF3: Changed rating: AMBER
Haematological malignancies cancer susceptibility v4.40 SH2B3 Arina Puzriakova edited their review of gene: SH2B3: Changed rating: AMBER
Haematological malignancies cancer susceptibility v4.40 HAVCR2 Arina Puzriakova edited their review of gene: HAVCR2: Changed rating: AMBER
Haematological malignancies cancer susceptibility v4.40 DNAH9 Arina Puzriakova edited their review of gene: DNAH9: Changed rating: AMBER
Haematological malignancies cancer susceptibility v4.40 DHX34 Arina Puzriakova edited their review of gene: DHX34: Changed rating: AMBER
Haematological malignancies cancer susceptibility v4.39 TCF3 Arina Puzriakova commented on gene: TCF3: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. Additional comments from reviewing GLHs: no clinical guidelines to manage the findings.
Haematological malignancies cancer susceptibility v4.39 SH2B3 Arina Puzriakova commented on gene: SH2B3
Haematological malignancies cancer susceptibility v4.39 POT1 Arina Puzriakova commented on gene: POT1: 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.
Haematological malignancies cancer susceptibility v4.39 KDM1A Arina Puzriakova commented on gene: KDM1A: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. Additional comments from reviewing GLHs: no clinical guidelines to manage the findings.
Haematological malignancies cancer susceptibility v4.39 HAVCR2 Arina Puzriakova commented on gene: HAVCR2
Haematological malignancies cancer susceptibility v4.39 DNAH9 Arina Puzriakova commented on gene: DNAH9
Haematological malignancies cancer susceptibility v4.39 DHX34 Arina Puzriakova commented on gene: DHX34
Haematological malignancies cancer susceptibility v4.38 POT1 Arina Puzriakova Source NHS GMS was added to POT1.
Source Expert Review Green was added to POT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v8.98 INTS11 Siying Lin gene: INTS11 was added
gene: INTS11 was added to Retinal disorders. Sources: Literature
Mode of inheritance for gene: INTS11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS11 were set to PMID: 41810893
Phenotypes for gene: INTS11 were set to Retinal dystrophy
Mode of pathogenicity for gene: INTS11 was set to Other
Added comment: PMID 41810893 describes 4 patients from 2 unrelated families with a distinct inner retinopathy associated with INTS11-associated neurodevelopmental disorder, supporting this gene as a cause of syndromic IRD.
Sources: Literature
Skeletal dysplasia v8.37 VPS33A Eleanor Williams Tag Q1_25_ promote_green was removed from gene: VPS33A.
Skeletal dysplasia v8.37 SLCO2A1 Eleanor Williams Tag Q2_25_ MOI was removed from gene: SLCO2A1.
Skeletal dysplasia v8.37 SLC13A1 Eleanor Williams Tag Q1_25_ promote_green was removed from gene: SLC13A1.
Skeletal dysplasia v8.37 RSPRY1 Eleanor Williams Tag Q1_25_ promote_green was removed from gene: RSPRY1.
Skeletal dysplasia v8.37 PTBP1 Eleanor Williams Tag Q3_25_promote_green was removed from gene: PTBP1.
Tag Q3_25_NHS_review was removed from gene: PTBP1.
Skeletal dysplasia v8.37 FGF4 Eleanor Williams Tag Q3_25_promote_green was removed from gene: FGF4.
Skeletal dysplasia v8.37 EVC2 Eleanor Williams Tag Q3_25_MOI was removed from gene: EVC2.
Skeletal dysplasia v8.37 DDR2 Eleanor Williams Tag Q1_25_ NHS_review was removed from gene: DDR2.
Tag Q1_25_ MOI was removed from gene: DDR2.
Skeletal dysplasia v8.37 CTGF Eleanor Williams Tag Q1_25_ promote_green was removed from gene: CTGF.
Skeletal dysplasia v8.37 VPS33A Eleanor Williams reviewed gene: VPS33A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v8.37 SLCO2A1 Eleanor Williams commented on gene: SLCO2A1: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Skeletal dysplasia v8.37 SLC13A1 Eleanor Williams reviewed gene: SLC13A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v8.37 RSPRY1 Eleanor Williams reviewed gene: RSPRY1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v8.37 PTBP1 Eleanor Williams reviewed gene: PTBP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v8.37 FGF4 Eleanor Williams commented on gene: FGF4: 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.
Skeletal dysplasia v8.37 EVC2 Eleanor Williams commented on gene: EVC2: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Skeletal dysplasia v8.37 DDR2 Eleanor Williams commented on gene: DDR2: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed and remains BIALLELIC, autosomal or pseudoautosomal. Unlikely that patients with WARBURG-CINOTTI SYNDROME woud be tested via a skeletal dysplasia test. Primary phenotype is not skeletal dysplasia but contractures.
Skeletal dysplasia v8.37 CTGF Eleanor Williams reviewed gene: CTGF: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Skeletal dysplasia v8.36 VPS33A Eleanor Williams Source NHS GMS was added to VPS33A.
Source Expert Review Green was added to VPS33A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v8.36 SLCO2A1 Eleanor Williams Mode of inheritance for gene SLCO2A1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v8.36 SLC13A1 Eleanor Williams Source NHS GMS was added to SLC13A1.
Source Expert Review Green was added to SLC13A1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v8.36 RSPRY1 Eleanor Williams Source NHS GMS was added to RSPRY1.
Source Expert Review Green was added to RSPRY1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v8.36 PTBP1 Eleanor Williams Source Expert Review Green was added to PTBP1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v8.36 FGF4 Eleanor Williams Source NHS GMS was added to FGF4.
Source Expert Review Green was added to FGF4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Skeletal dysplasia v8.36 EVC2 Eleanor Williams Mode of inheritance for gene EVC2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Skeletal dysplasia v8.36 CTGF Eleanor Williams Source NHS GMS was added to CTGF.
Source Expert Review Green was added to CTGF.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v6.157 SCN4A Achchuthan Shanmugasundram Tag Q2_25_ MOI was removed from gene: SCN4A.
Fetal anomalies v6.157 PTBP1 Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: PTBP1.
Fetal anomalies v6.157 PTBP1 Achchuthan Shanmugasundram Deleted their review
Fetal anomalies v6.157 MYH3 Achchuthan Shanmugasundram Tag Q3_25_MOI was removed from gene: MYH3.
Fetal anomalies v6.157 LMNB2 Achchuthan Shanmugasundram Tag Q2_25_ MOI was removed from gene: LMNB2.
Tag Q2_25_ NHS_review was removed from gene: LMNB2.
Fetal anomalies v6.157 LMNB2 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 MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted. The GMS reviewers noted as follows: Pathogenic monoallelic missense variants are causative of primary microcephaly. Homozygous loss-of-function variant reported in two related newborns with severe brain development abnormalities and perinatal death, phenotype consistent with Lmnb2-deficient mouse models (PMID:40011009). At least one further unrelated case is required to confirm an additional biallelic loss-of-function mechanism for LMNB2-related disease (mechanism of pathogenicity for monoallelic variants is uncertain).; to: After NHS Genomic Medicine Service consideration, the mode of inheritance of this gene has not been changed and remains MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted.

The GMS reviewers noted as follows:
Pathogenic monoallelic missense variants are causative of primary microcephaly. Homozygous loss-of-function variant reported in two related newborns with severe brain development abnormalities and perinatal death, phenotype consistent with Lmnb2-deficient mouse models (PMID:40011009). At least one further unrelated case is required to confirm an additional biallelic loss-of-function mechanism for LMNB2-related disease (mechanism of pathogenicity for monoallelic variants is uncertain).
Fetal anomalies v6.157 GPKOW Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: GPKOW.
Fetal anomalies v6.157 GPKOW Achchuthan Shanmugasundram Deleted their review
Fetal anomalies v6.157 GPKOW Achchuthan Shanmugasundram Deleted their comment
Fetal anomalies v6.157 EVC2 Achchuthan Shanmugasundram Tag Q3_25_MOI was removed from gene: EVC2.
Fetal anomalies v6.157 EVC2 Achchuthan Shanmugasundram changed review comment from: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval. The GMS reviewers noted as follows: Heterozygous variants cause Weyers acrofacial dysostosis: dental anomalies, nail dystrophy, postaxial polydactyly, and mild short stature. Polydactyly detectable prenatally. Hence, monoallelic MOI should be added.; to: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

The GMS reviewers noted as follows:
Heterozygous variants cause Weyers acrofacial dysostosis: dental anomalies, nail dystrophy, postaxial polydactyly, and mild short stature. Polydactyly detectable prenatally. Hence, monoallelic MOI should be added.
Fetal anomalies v6.157 MED12 Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: MED12.
Fetal anomalies v6.157 MED12 Achchuthan Shanmugasundram changed review comment from: The mode of inheritance of this gene has been updated to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) following NHS Genomic Medicine Service approval. The GMS reviewers noted as follows: Multiple reports of prenatal features in female pregnancies e.g. PMID:3970286; PMID:40884785,PMID:34987808.; to: The mode of inheritance of this gene has been updated to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) following NHS Genomic Medicine Service approval.

The GMS reviewers noted as follows: Multiple reports of prenatal features in female pregnancies e.g. PMID:3970286; PMID:40884785,PMID:34987808.
Fetal anomalies v6.157 LIFR Achchuthan Shanmugasundram Tag to_be_confirmed_NHSE was removed from gene: LIFR.
Fetal anomalies v6.157 LIFR 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 GMS reviewers noted as follows: Biallelic LoF variants are associated with skeletal Stuve-Wiedemann syndrome/Schwartz-Jampel type 2 syndromes. Monoallelic variants are reported in association with CAKUT - de novo frameshift in one case with bilateral CAKUT and two rare missense variants in 3 further cases (PMID:28334964). Gene is not depleted for LoF variants and >50 variants that are classified as (likely) pathogenic in ClinVar are present in the heterozygous state in gnomAD. If there is a genuine association between monoallelic LoF variants and CAKUT, penetrance must be low. MOI should remain as biallelic only.; 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 GMS reviewers noted as follows:
Biallelic LoF variants are associated with skeletal Stuve-Wiedemann syndrome/Schwartz-Jampel type 2 syndromes. Monoallelic variants are reported in association with CAKUT - de novo frameshift in one case with bilateral CAKUT and two rare missense variants in 3 further cases (PMID:28334964). Gene is not depleted for LoF variants and >50 variants that are classified as (likely) pathogenic in ClinVar are present in the heterozygous state in gnomAD. If there is a genuine association between monoallelic LoF variants and CAKUT, penetrance must be low. MOI should remain as biallelic only.
Fetal anomalies v6.157 SIX5 Achchuthan Shanmugasundram Tag Q3_25_expert_review was removed from gene: SIX5.
Tag Q3_25_demote_red was removed from gene: SIX5.
Fetal anomalies v6.157 SIX5 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval. The GMS reviewers noted as follows: Disputed by ClinGen and now red on most other panels. Variants in the literature have high frequency in gnomad.; to: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.

The GMS reviewers noted as follows:
Disputed by ClinGen and now red on most other panels. Variants in the literature have high frequency in gnomad.
Fetal anomalies v6.157 PLD1 Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: PLD1.
Tag Q3_25_expert_review was removed from gene: PLD1.
Fetal anomalies v6.157 PLD1 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval. The GMS reviewers noted as follows: ClinGen - definitive. Green on Aus panel. Fetal cases previously reported. It should be noted however that isolated cardiac is not an idication for R21 but there is one with abdominal effusions . It was downgraded due to downgrade on other panels so all should go green if fetal anomalies does.; to: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

The GMS reviewers noted as follows:
ClinGen - definitive. Green on Aus panel. Fetal cases previously reported. It should be noted however that isolated cardiac is not an idication for R21 but there is one with abdominal effusions . It was downgraded due to downgrade on other panels so all should go green if fetal anomalies does.
Fetal anomalies v6.157 LINC01082 Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: LINC01082.
Tag Q3_25_expert_review was removed from gene: LINC01082.
Tag Q3_25_NHS_review was removed from gene: LINC01082.
Fetal anomalies v6.157 LINC01082 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval. The GMS reviewers noted as follows: Deletions of LINC01081/LINC01082 cause same phenotype as variants in FOXF1, which is green on the fetal anomalies panel. No reports of sequence variants in LINC01081/LINC01082. Deletions may not be detectable by exome sequencing but gene should be added to panel in anticipation of WGS.; to: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.

The GMS reviewers noted as follows:
Deletions of LINC01081/LINC01082 cause same phenotype as variants in FOXF1, which is green on the fetal anomalies panel. No reports of sequence variants in LINC01081/LINC01082. Deletions may not be detectable by exome sequencing but gene should be added to panel in anticipation of WGS.
Fetal anomalies v6.157 LINC01081 Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: LINC01081.
Tag Q3_25_expert_review was removed from gene: LINC01081.
Tag Q3_25_NHS_review was removed from gene: LINC01081.
Fetal anomalies v6.157 LINC01081 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval. The GMS reviewers noted as follows: Deletions of LINC01081/LINC01082 cause same phenotype as variants in FOXF1, which is green on the fetal anomalies panel. No reports of sequence variants in LINC01081/LINC01082. Deletions may not be detectable by exome sequencing but gene should be added to panel in anticipation of WGS.; to: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.

The GMS reviewers noted as follows:
Deletions of LINC01081/LINC01082 cause same phenotype as variants in FOXF1, which is green on the fetal anomalies panel. No reports of sequence variants in LINC01081/LINC01082. Deletions may not be detectable by exome sequencing but gene should be added to panel in anticipation of WGS.
Fetal anomalies v6.157 KIAA0556 Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: KIAA0556.
Tag Q3_25_expert_review was removed from gene: KIAA0556.
Fetal anomalies v6.157 KIAA0556 Achchuthan Shanmugasundram Deleted their comment
Fetal anomalies v6.157 EMX2 Achchuthan Shanmugasundram Tag Q3_25_expert_review was removed from gene: EMX2.
Tag Q3_25_demote_amber was removed from gene: EMX2.
Fetal anomalies v6.157 EMX2 Achchuthan Shanmugasundram changed review comment from: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval. The GMS reviewers noted as follows: Multiple patients reported in 1997 with schizencephaly and de novo EMX2 variants detected by targeted sequencing (PMID:9359037). However, subsequent sequencing studies in schizencephaly cohorts have not found any further cases (84 cases in PMID:17506092, 39 cases in PMID:18409201, 52 cases in PMID:20157829). Red on Australian PanelApp. Hence, the gene should be demoted from green rating.; to: The rating of this gene has been updated to amber following NHS Genomic Medicine Service approval.

The GMS reviewers noted as follows:
Multiple patients reported in 1997 with schizencephaly and de novo EMX2 variants detected by targeted sequencing (PMID:9359037). However, subsequent sequencing studies in schizencephaly cohorts have not found any further cases (84 cases in PMID:17506092, 39 cases in PMID:18409201, 52 cases in PMID:20157829). Red on Australian PanelApp. Hence, the gene should be demoted from green rating.
Fetal anomalies v6.157 DISP1 Achchuthan Shanmugasundram Tag Q3_25_MOI was removed from gene: DISP1.
Tag Q3_25_expert_review was removed from gene: DISP1.
Fetal anomalies v6.157 DISP1 Achchuthan Shanmugasundram changed review comment from: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval. The GMS reviewers noted as follows: Listed as both AD and AR in OMIM, with biallelic variants described as causal and monoallelic as a risk factor. PMID:38529886 - DISP1 monoallelic LoF or biallelic variants associated with minor forms of HPE (orofacial cleft, central incisor); in severe HPE, DISP1 variants occur together with a variant in another HPE gene. Green for monoallelic/biallelic on Australian panel.; to: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

The GMS reviewers noted as follows:
Listed as both AD and AR in OMIM, with biallelic variants described as causal and monoallelic as a risk factor. PMID:38529886 - DISP1 monoallelic LoF or biallelic variants associated with minor forms of HPE (orofacial cleft, central incisor); in severe HPE, DISP1 variants occur together with a variant in another HPE gene. Green for monoallelic/biallelic on Australian panel.
Fetal anomalies v6.157 SIX5 Achchuthan Shanmugasundram reviewed gene: SIX5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v6.157 SCN4A Achchuthan Shanmugasundram commented on gene: SCN4A
Fetal anomalies v6.157 PTBP1 Achchuthan Shanmugasundram reviewed gene: PTBP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v6.157 PLD1 Achchuthan Shanmugasundram edited their review of gene: PLD1: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval. The GMS reviewers noted as follows: ClinGen - definitive. Green on Aus panel. Fetal cases previously reported. It should be noted however that isolated cardiac is not an idication for R21 but there is one with abdominal effusions . It was downgraded due to downgrade on other panels so all should go green if fetal anomalies does.; Changed rating: GREEN
Fetal anomalies v6.157 MYH3 Achchuthan Shanmugasundram commented on gene: MYH3
Fetal anomalies v6.157 MED12 Achchuthan Shanmugasundram commented on gene: MED12
Fetal anomalies v6.157 LMNB2 Achchuthan Shanmugasundram commented on gene: LMNB2
Fetal anomalies v6.157 LINC01082 Achchuthan Shanmugasundram reviewed gene: LINC01082: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v6.157 LINC01081 Achchuthan Shanmugasundram reviewed gene: LINC01081: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v6.157 LIFR Achchuthan Shanmugasundram commented on gene: LIFR
Fetal anomalies v6.157 KIAA0556 Achchuthan Shanmugasundram edited their review of gene: KIAA0556: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Fetal anomalies v6.157 GPKOW Achchuthan Shanmugasundram reviewed gene: GPKOW: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v6.157 EVC2 Achchuthan Shanmugasundram commented on gene: EVC2
Fetal anomalies v6.157 EMX2 Achchuthan Shanmugasundram reviewed gene: EMX2: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Fetal anomalies v6.157 DISP1 Achchuthan Shanmugasundram commented on gene: DISP1
Fetal anomalies v6.156 SIX5 Achchuthan Shanmugasundram Source NHS GMS was added to SIX5.
Source Expert Review Red was added to SIX5.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Fetal anomalies v6.156 SCN4A Achchuthan Shanmugasundram Source NHS GMS was added to SCN4A.
Mode of inheritance for gene SCN4A was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v6.156 PLD1 Achchuthan Shanmugasundram Source Expert Review Green was added to PLD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v6.156 MYH3 Achchuthan Shanmugasundram Source NHS GMS was added to MYH3.
Mode of inheritance for gene MYH3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v6.156 MED12 Achchuthan Shanmugasundram Source NHS GMS was added to MED12.
Mode of inheritance for gene MED12 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Fetal anomalies v6.156 LINC01082 Achchuthan Shanmugasundram Source Expert Review Green was added to LINC01082.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v6.156 LINC01081 Achchuthan Shanmugasundram Source Expert Review Green was added to LINC01081.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Fetal anomalies v6.156 GPKOW Achchuthan Shanmugasundram Source NHS GMS was added to GPKOW.
Fetal anomalies v6.156 EVC2 Achchuthan Shanmugasundram Source NHS GMS was added to EVC2.
Mode of inheritance for gene EVC2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v6.156 EMX2 Achchuthan Shanmugasundram Source NHS GMS was added to EMX2.
Source Expert Review Amber was added to EMX2.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Fetal anomalies v6.156 DISP1 Achchuthan Shanmugasundram Source NHS GMS was added to DISP1.
Mode of inheritance for gene DISP1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v8.33 TNR Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: TNR.
Childhood onset hereditary spastic paraplegia v8.33 SOD1 Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: SOD1.
Childhood onset hereditary spastic paraplegia v8.33 OGDHL Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: OGDHL.
Childhood onset hereditary spastic paraplegia v8.33 NOTCH3 Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: NOTCH3.
Tag Q3_25_NHS_review was removed from gene: NOTCH3.
Childhood onset hereditary spastic paraplegia v8.33 INPP4A Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: INPP4A.
Childhood onset hereditary spastic paraplegia v8.33 FLVCR1 Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: FLVCR1.
Childhood onset hereditary spastic paraplegia v8.33 EXOSC8 Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: EXOSC8.
Skeletal ciliopathies v6.7 EVC2 Eleanor Williams Tag Q3_25_MOI was removed from gene: EVC2.
Skeletal ciliopathies v6.7 EVC2 Eleanor Williams commented on gene: EVC2: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Skeletal ciliopathies v6.6 EVC2 Eleanor Williams Source NHS GMS was added to EVC2.
Mode of inheritance for gene EVC2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v8.33 ATL1 Achchuthan Shanmugasundram Tag Q3_25_MOI was removed from gene: ATL1.
Severe microcephaly v8.34 WARS Eleanor Williams Tag Q3_25_promote_green was removed from gene: WARS.
Severe microcephaly v8.34 TMEM167A Eleanor Williams Tag Q3_25_promote_green was removed from gene: TMEM167A.
Severe microcephaly v8.34 SPOUT1 Eleanor Williams Tag Q1_25_ promote_green was removed from gene: SPOUT1.
Severe microcephaly v8.34 PNPLA8 Eleanor Williams Tag Q1_25_ promote_green was removed from gene: PNPLA8.
Severe microcephaly v8.34 MRPL49 Eleanor Williams Tag Q2_25_ promote_green was removed from gene: MRPL49.
Childhood onset hereditary spastic paraplegia v8.33 SPTSSA Achchuthan Shanmugasundram Tag Q1_25_ promote_green was removed from gene: SPTSSA.
Severe microcephaly v8.34 LMNB2 Eleanor Williams Tag Q2_25_ MOI was removed from gene: LMNB2.
Severe microcephaly v8.34 INPP4A Eleanor Williams Tag Q3_25_promote_green was removed from gene: INPP4A.
Severe microcephaly v8.34 GTF3C3 Eleanor Williams Tag Q1_25_ promote_green was removed from gene: GTF3C3.
Severe microcephaly v8.34 FLVCR1 Eleanor Williams Tag Q3_25_promote_green was removed from gene: FLVCR1.
Severe microcephaly v8.34 EEF1D Eleanor Williams Tag Q2_25_ promote_green was removed from gene: EEF1D.
Tag Q2_25_ NHS_review was removed from gene: EEF1D.
Severe microcephaly v8.34 CRNKL1 Eleanor Williams Tag Q3_25_promote_green was removed from gene: CRNKL1.
Childhood onset hereditary spastic paraplegia v8.33 SPAST Achchuthan Shanmugasundram Tag Q1_25_ MOI was removed from gene: SPAST.
Childhood onset hereditary spastic paraplegia v8.33 TNR Achchuthan Shanmugasundram reviewed gene: TNR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood onset hereditary spastic paraplegia v8.33 SPTSSA Achchuthan Shanmugasundram edited their review of gene: SPTSSA: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Childhood onset hereditary spastic paraplegia v8.33 SPAST Achchuthan Shanmugasundram commented on gene: SPAST
Childhood onset hereditary spastic paraplegia v8.33 SOD1 Achchuthan Shanmugasundram reviewed gene: SOD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood onset hereditary spastic paraplegia v8.33 OGDHL Achchuthan Shanmugasundram reviewed gene: OGDHL: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood onset hereditary spastic paraplegia v8.33 NOTCH3 Achchuthan Shanmugasundram commented on gene: NOTCH3: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v8.33 INPP4A Achchuthan Shanmugasundram commented on gene: INPP4A: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v8.33 FLVCR1 Achchuthan Shanmugasundram reviewed gene: FLVCR1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood onset hereditary spastic paraplegia v8.33 EXOSC8 Achchuthan Shanmugasundram reviewed gene: EXOSC8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood onset hereditary spastic paraplegia v8.33 BHLHE22 Achchuthan Shanmugasundram commented on gene: BHLHE22
Childhood onset hereditary spastic paraplegia v8.33 ATL1 Achchuthan Shanmugasundram commented on gene: ATL1: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Childhood onset hereditary spastic paraplegia v8.32 ATXN10_ATTCT Achchuthan Shanmugasundram reviewed STR: ATXN10_ATTCT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Childhood onset hereditary spastic paraplegia v8.32 ATXN10_ATTCT Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from STR: ATXN10_ATTCT.
Tag Q2_25_expert_review was removed from STR: ATXN10_ATTCT.
Childhood onset hereditary spastic paraplegia v8.32 ATXN10_ATTCT Achchuthan Shanmugasundram Classified STR: ATXN10_ATTCT as Green List (high evidence)
Childhood onset hereditary spastic paraplegia v8.32 ATXN10_ATTCT Achchuthan Shanmugasundram Str: atxn10_attct has been classified as Green List (High Evidence).
Childhood onset hereditary spastic paraplegia v8.31 TNR Achchuthan Shanmugasundram Source NHS GMS was added to TNR.
Source Expert Review Green was added to TNR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v8.31 SPTSSA Achchuthan Shanmugasundram Source NHS GMS was added to SPTSSA.
Source Expert Review Green was added to SPTSSA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v8.31 SPAST Achchuthan Shanmugasundram Mode of inheritance for gene SPAST was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia v8.31 SOD1 Achchuthan Shanmugasundram Source NHS GMS was added to SOD1.
Source Expert Review Green was added to SOD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v8.31 OGDHL Achchuthan Shanmugasundram Source NHS GMS was added to OGDHL.
Source Expert Review Green was added to OGDHL.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v8.31 NOTCH3 Achchuthan Shanmugasundram Source Expert Review Green was added to NOTCH3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v8.31 INPP4A Achchuthan Shanmugasundram Source NHS GMS was added to INPP4A.
Source Expert Review Green was added to INPP4A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v8.31 FLVCR1 Achchuthan Shanmugasundram Source NHS GMS was added to FLVCR1.
Source Expert Review Green was added to FLVCR1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v8.31 EXOSC8 Achchuthan Shanmugasundram Source NHS GMS was added to EXOSC8.
Source Expert Review Green was added to EXOSC8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset hereditary spastic paraplegia v8.31 ATL1 Achchuthan Shanmugasundram Mode of inheritance for gene ATL1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Severe microcephaly v8.34 WARS Eleanor Williams commented on gene: WARS: 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.
Severe microcephaly v8.34 TMEM167A Eleanor Williams reviewed gene: TMEM167A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v8.34 SPOUT1 Eleanor Williams reviewed gene: SPOUT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v8.34 PNPLA8 Eleanor Williams reviewed gene: PNPLA8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v8.34 MRPL49 Eleanor Williams reviewed gene: MRPL49: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v8.34 LMNB2 Eleanor Williams commented on gene: LMNB2
Severe microcephaly v8.34 INPP4A Eleanor Williams reviewed gene: INPP4A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v8.34 GTF3C3 Eleanor Williams reviewed gene: GTF3C3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v8.34 FLVCR1 Eleanor Williams commented on gene: FLVCR1: 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.
Severe microcephaly v8.34 EEF1D Eleanor Williams reviewed gene: EEF1D: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v8.34 CRNKL1 Eleanor Williams reviewed gene: CRNKL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Severe microcephaly v8.33 WARS Eleanor Williams Source NHS GMS was added to WARS.
Source Expert Review Green was added to WARS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v8.33 TMEM167A Eleanor Williams Source NHS GMS was added to TMEM167A.
Source Expert Review Green was added to TMEM167A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v8.33 SPOUT1 Eleanor Williams Source NHS GMS was added to SPOUT1.
Source Expert Review Green was added to SPOUT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v8.33 PNPLA8 Eleanor Williams Source NHS GMS was added to PNPLA8.
Source Expert Review Green was added to PNPLA8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v8.33 MRPL49 Eleanor Williams Source NHS GMS was added to MRPL49.
Source Expert Review Green was added to MRPL49.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v8.33 LMNB2 Eleanor Williams Source NHS GMS was added to LMNB2.
Mode of inheritance for gene LMNB2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Severe microcephaly v8.33 INPP4A Eleanor Williams Source NHS GMS was added to INPP4A.
Source Expert Review Green was added to INPP4A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v8.33 GTF3C3 Eleanor Williams Source NHS GMS was added to GTF3C3.
Source Expert Review Green was added to GTF3C3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v8.33 FLVCR1 Eleanor Williams Source NHS GMS was added to FLVCR1.
Source Expert Review Green was added to FLVCR1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v8.33 EEF1D Eleanor Williams Source NHS GMS was added to EEF1D.
Source Expert Review Green was added to EEF1D.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Severe microcephaly v8.33 CRNKL1 Eleanor Williams Source NHS GMS was added to CRNKL1.
Source Expert Review Green was added to CRNKL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v5.17 POC5 Eleanor Williams Tag Q3_25_promote_green was removed from gene: POC5.
Rhabdomyolysis and metabolic muscle disorders v5.17 CASQ1 Eleanor Williams Tag Q3_25_promote_green was removed from gene: CASQ1.
Rhabdomyolysis and metabolic muscle disorders v5.17 ATP2A2 Eleanor Williams Tag Q1_25_ promote_green was removed from gene: ATP2A2.
Rhabdomyolysis and metabolic muscle disorders v5.17 ATP2A2 Eleanor Williams Mode of inheritance for gene: ATP2A2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rhabdomyolysis and metabolic muscle disorders v5.16 AMPD1 Eleanor Williams Tag Q3_25_expert_review was removed from gene: AMPD1.
Tag Q3_25_demote_red was removed from gene: AMPD1.
Rhabdomyolysis and metabolic muscle disorders v5.16 POC5 Eleanor Williams reviewed gene: POC5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Rhabdomyolysis and metabolic muscle disorders v5.16 CASQ1 Eleanor Williams reviewed gene: CASQ1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Rhabdomyolysis and metabolic muscle disorders v5.16 ATP2A2 Eleanor Williams reviewed gene: ATP2A2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Rhabdomyolysis and metabolic muscle disorders v5.16 AMPD1 Eleanor Williams edited their review of gene: AMPD1: Added comment: The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.; Changed rating: RED
Rhabdomyolysis and metabolic muscle disorders v5.15 POC5 Eleanor Williams Source NHS GMS was added to POC5.
Source Expert Review Green was added to POC5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v5.15 CASQ1 Eleanor Williams Source NHS GMS was added to CASQ1.
Source Expert Review Green was added to CASQ1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v5.15 ATP2A2 Eleanor Williams Source NHS GMS was added to ATP2A2.
Source Expert Review Green was added to ATP2A2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Rhabdomyolysis and metabolic muscle disorders v5.15 AMPD1 Eleanor Williams Source Expert Review Red was added to AMPD1.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Retinal disorders v8.98 PAX6 Eleanor Williams Tag Q3_25_promote_green was removed from gene: PAX6.
Tag Q3_25_expert_review was removed from gene: PAX6.
Tag to_be_confirmed_NHSE tag was added to gene: PAX6.
Retinal disorders v8.98 FRMD7 Eleanor Williams Tag Q3_25_promote_green was removed from gene: FRMD7.
Tag Q3_25_expert_review was removed from gene: FRMD7.
Tag to_be_confirmed_NHSE tag was added to gene: FRMD7.
Retinal disorders v8.98 VSX2 Eleanor Williams Tag Q3_25_promote_green was removed from gene: VSX2.
Retinal disorders v8.98 THRB Eleanor Williams Tag Q2_25_ promote_green was removed from gene: THRB.
Tag Q2_25_ NHS_review was removed from gene: THRB.
Hereditary ataxia with onset in adulthood v8.26 RAB3A Arina Puzriakova Tag Q2_25_ promote_green was removed from gene: RAB3A.
Tag Q2_25_ NHS_review was removed from gene: RAB3A.
Hereditary ataxia with onset in adulthood v8.26 NPTX1 Arina Puzriakova Tag Q2_25_ promote_green was removed from gene: NPTX1.
Tag Q2_25_ NHS_review was removed from gene: NPTX1.
Hereditary ataxia with onset in adulthood v8.26 NEU1 Arina Puzriakova Tag Q2_25_ promote_green was removed from gene: NEU1.
Tag Q2_25_ NHS_review was removed from gene: NEU1.
Hereditary ataxia with onset in adulthood v8.26 MFSD8 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: MFSD8.
Hereditary ataxia with onset in adulthood v8.26 GDAP2 Arina Puzriakova Tag Q4_24_NHS_review was removed from gene: GDAP2.
Tag Q4_24_promote_green was removed from gene: GDAP2.
Retinal disorders v8.98 SPG11 Eleanor Williams Tag Q3_25_promote_green was removed from gene: SPG11.
Tag Q3_25_NHS_review was removed from gene: SPG11.
Hereditary ataxia with onset in adulthood v8.26 FAT2 Arina Puzriakova Tag Q2_25_ promote_green was removed from gene: FAT2.
Tag Q2_25_ NHS_review was removed from gene: FAT2.
Hereditary ataxia with onset in adulthood v8.26 SPR Arina Puzriakova Publications for gene: SPR were set to
Hereditary ataxia with onset in adulthood v8.25 SPR Arina Puzriakova Tag Q1_25_ MOI was removed from gene: SPR.
Tag Q1_25_ demote_red was removed from gene: SPR.
Tag Q1_25_ expert_review was removed from gene: SPR.
Retinal disorders v8.98 POC5 Eleanor Williams Tag Q3_25_promote_green was removed from gene: POC5.
Tag Q3_25_NHS_review was removed from gene: POC5.
Retinal disorders v8.98 IDH3G Eleanor Williams Added comment: Comment on phenotypes: OMIM phenotype accessed on 11 March 2026
Retinal disorders v8.98 IDH3G Eleanor Williams Phenotypes for gene: IDH3G were changed from X-linked retinitis pigmentosa to Retinitis pigmentosa 99, OMIM:301148, retinitis pigmentosa 99, MONDO:0978291
Hereditary ataxia with onset in adulthood v8.25 EXOSC8 Arina Puzriakova Tag Q3_25_expert_review was removed from gene: EXOSC8.
Tag Q3_25_demote_red was removed from gene: EXOSC8.
Retinal disorders v8.97 IDH3G Eleanor Williams Tag Q1_25_ promote_green was removed from gene: IDH3G.
Retinal disorders v8.97 DHX38 Eleanor Williams Tag Q3_25_promote_green was removed from gene: DHX38.
Hereditary ataxia with onset in adulthood v8.25 SPR Achchuthan Shanmugasundram reviewed gene: SPR: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary ataxia with onset in adulthood v8.25 RAB3A Achchuthan Shanmugasundram reviewed gene: RAB3A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary ataxia with onset in adulthood v8.25 NPTX1 Achchuthan Shanmugasundram commented on gene: NPTX1: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v8.25 NEU1 Achchuthan Shanmugasundram reviewed gene: NEU1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary ataxia with onset in adulthood v8.25 MFSD8 Achchuthan Shanmugasundram reviewed gene: MFSD8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary ataxia with onset in adulthood v8.25 GDAP2 Achchuthan Shanmugasundram reviewed gene: GDAP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hereditary ataxia with onset in adulthood v8.25 FAT2 Achchuthan Shanmugasundram commented on gene: FAT2: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Hereditary ataxia with onset in adulthood v8.25 EXOSC8 Achchuthan Shanmugasundram reviewed gene: EXOSC8: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v8.97 C19orf44 Eleanor Williams Tag Q1_25_ NHS_review was removed from gene: C19orf44.
Tag Q1_25_ promote_green was removed from gene: C19orf44.
Hereditary ataxia with onset in adulthood v8.24 SPR Arina Puzriakova Source Expert Review Red was added to SPR.
Mode of inheritance for gene SPR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Rating Changed from Green List (high evidence) to Red List (low evidence)
Hereditary ataxia with onset in adulthood v8.24 RAB3A Arina Puzriakova Source NHS GMS was added to RAB3A.
Source Expert Review Green was added to RAB3A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary ataxia with onset in adulthood v8.24 NPTX1 Arina Puzriakova Source NHS GMS was added to NPTX1.
Source Expert Review Green was added to NPTX1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary ataxia with onset in adulthood v8.24 NEU1 Arina Puzriakova Source Expert Review Green was added to NEU1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary ataxia with onset in adulthood v8.24 MFSD8 Arina Puzriakova Source Expert Review Green was added to MFSD8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary ataxia with onset in adulthood v8.24 GDAP2 Arina Puzriakova Source Expert Review Green was added to GDAP2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary ataxia with onset in adulthood v8.24 FAT2 Arina Puzriakova Source NHS GMS was added to FAT2.
Source Expert Review Green was added to FAT2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Hereditary ataxia with onset in adulthood v8.24 EXOSC8 Arina Puzriakova Source Expert Review Red was added to EXOSC8.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Retinal disorders v8.97 AP5Z1 Eleanor Williams Tag Q1_25_ NHS_review was removed from gene: AP5Z1.
Tag Q1_25_ promote_green was removed from gene: AP5Z1.
Retinal disorders v8.97 DYRK1A Eleanor Williams Tag Q3_25_promote_green was removed from gene: DYRK1A.
Tag Q3_25_NHS_review was removed from gene: DYRK1A.
Retinal disorders v8.97 RNU6-9 Eleanor Williams Tag Q3_25_promote_green was removed from gene: RNU6-9.
Retinal disorders v8.97 RNU6-8 Eleanor Williams Tag Q3_25_promote_green was removed from gene: RNU6-8.
Retinal disorders v8.97 RNU6-2 Eleanor Williams Tag Q3_25_promote_green was removed from gene: RNU6-2.
Retinal disorders v8.97 RNU6-1 Eleanor Williams Tag Q3_25_promote_green was removed from gene: RNU6-1.
Retinal disorders v8.97 RNU4-2 Eleanor Williams Tag Q3_25_promote_green was removed from gene: RNU4-2.
Retinal disorders v8.97 TBC1D32 Eleanor Williams Tag Q2_25_ promote_green was removed from gene: TBC1D32.
Early onset or syndromic epilepsy v8.139 WDR47 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: WDR47.
Early onset or syndromic epilepsy v8.139 UNC13A Arina Puzriakova Tag Q3_25_promote_green was removed from gene: UNC13A.
Retinal disorders v8.97 CYP2U1 Eleanor Williams Tag Q3_25_promote_green was removed from gene: CYP2U1.
Retinal disorders v8.97 UNC119 Eleanor Williams Tag Q3_25_expert_review was removed from gene: UNC119.
Tag Q3_25_demote_amber was removed from gene: UNC119.
Retinal disorders v8.97 SAG Eleanor Williams Tag Q3_25_MOI was removed from gene: SAG.
Retinal disorders v8.97 RLBP1 Eleanor Williams Tag Q3_25_MOI was removed from gene: RLBP1.
Retinal disorders v8.97 RDH5 Eleanor Williams Tag Q3_25_MOI was removed from gene: RDH5.
Retinal disorders v8.97 KIAA1549 Eleanor Williams Tag Q3_25_MOI was removed from gene: KIAA1549.
Early onset or syndromic epilepsy v8.139 UGGT1 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: UGGT1.
Early onset or syndromic epilepsy v8.139 UBR5 Arina Puzriakova Tag dd_review was removed from gene: UBR5.
Tag Q3_25_promote_green was removed from gene: UBR5.
Early onset or syndromic epilepsy v8.139 TRPM7 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: TRPM7.
Early onset or syndromic epilepsy v8.139 TMEM167A Arina Puzriakova Tag Q3_25_promote_green was removed from gene: TMEM167A.
Early onset or syndromic epilepsy v8.139 TARS2 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: TARS2.
Early onset or syndromic epilepsy v8.139 SPOUT1 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: SPOUT1.
Early onset or syndromic epilepsy v8.139 RYR3 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: RYR3.
Early onset or syndromic epilepsy v8.139 RNU5B-1 Arina Puzriakova Tag dd_review was removed from gene: RNU5B-1.
Tag Q3_25_promote_green was removed from gene: RNU5B-1.
Early onset or syndromic epilepsy v8.139 RNU2-2P Arina Puzriakova Tag dd_review was removed from gene: RNU2-2P.
Tag Q2_25_ promote_green was removed from gene: RNU2-2P.
Early onset or syndromic epilepsy v8.139 PPP2R5C Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: PPP2R5C.
Early onset or syndromic epilepsy v8.139 PPP2R2B Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: PPP2R2B.
Early onset or syndromic epilepsy v8.139 PPOX Arina Puzriakova Tag Q3_25_promote_green was removed from gene: PPOX.
Early onset or syndromic epilepsy v8.139 PNPLA8 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: PNPLA8.
Early onset or syndromic epilepsy v8.139 PABPC1 Arina Puzriakova Tag Q4_24_MOI was removed from gene: PABPC1.
Early onset or syndromic epilepsy v8.139 NOTCH3 Arina Puzriakova Tag dd_review was removed from gene: NOTCH3.
Tag Q3_25_promote_green was removed from gene: NOTCH3.
Early onset or syndromic epilepsy v8.139 MT-TK Arina Puzriakova Tag Q3_25_promote_green was removed from gene: MT-TK.
Tag Q3_25_NHS_review was removed from gene: MT-TK.
Early onset or syndromic epilepsy v8.139 MARK2 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: MARK2.
Early onset or syndromic epilepsy v8.139 LSS Arina Puzriakova Tag Q3_25_promote_green was removed from gene: LSS.
Early onset or syndromic epilepsy v8.139 LGI1 Arina Puzriakova Tag Q3_25_MOI was removed from gene: LGI1.
Early onset or syndromic epilepsy v8.139 LAMC3 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: LAMC3.
Early onset or syndromic epilepsy v8.139 KCND3 Arina Puzriakova Tag dd_review was removed from gene: KCND3.
Tag Q3_25_promote_green was removed from gene: KCND3.
Early onset or syndromic epilepsy v8.139 INPP4A Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: INPP4A.
Intellectual disability v9.297 GTF3C3 Arina Puzriakova Added comment: Comment on phenotypes: OMIM phenotype accessed on 11-03-2026
Intellectual disability v9.297 GTF3C3 Arina Puzriakova Phenotypes for gene: GTF3C3 were changed from Global developmental delay; Intellectual disability; Seizures to Neurodevelopmental disorder with dysmorphic facies, brain anomalies, and seizures, OMIM:621201
Severe microcephaly v8.32 GTF3C3 Arina Puzriakova Added comment: Comment on phenotypes: OMIM phenotype accessed on 11-03-2026
Severe microcephaly v8.32 GTF3C3 Arina Puzriakova Phenotypes for gene: GTF3C3 were changed from Global developmental delay; Intellectual disability; Seizures to Neurodevelopmental disorder with dysmorphic facies, brain anomalies, and seizures, OMIM:621201
Early onset or syndromic epilepsy v8.139 GTF3C3 Arina Puzriakova Added comment: Comment on phenotypes: OMIM phenotype accessed on 11-03-2026
Early onset or syndromic epilepsy v8.139 GTF3C3 Arina Puzriakova Phenotypes for gene: GTF3C3 were changed from Global developmental delay; Intellectual disability; Seizures to Neurodevelopmental disorder with dysmorphic facies, brain anomalies, and seizures, OMIM:621201
Early onset or syndromic epilepsy v8.138 GTF3C3 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: GTF3C3.
Early onset or syndromic epilepsy v8.138 GLS Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: GLS.
Early onset or syndromic epilepsy v8.138 FLVCR1 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: FLVCR1.
Early onset or syndromic epilepsy v8.138 EPB41L3 Arina Puzriakova Tag Q2_25_ promote_green was removed from gene: EPB41L3.
Tag Q2_25_ NHS_review was removed from gene: EPB41L3.
Early onset or syndromic epilepsy v8.138 ELFN1 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: ELFN1.
Early onset or syndromic epilepsy v8.138 EEFSEC Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: EEFSEC.
Early onset or syndromic epilepsy v8.138 CTSF Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: CTSF.
Early onset or syndromic epilepsy v8.138 CRNKL1 Arina Puzriakova Mode of pathogenicity for gene: CRNKL1 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Early onset or syndromic epilepsy v8.137 CRNKL1 Arina Puzriakova Tag dd_review was removed from gene: CRNKL1.
Tag Q3_25_promote_green was removed from gene: CRNKL1.
Early onset or syndromic epilepsy v8.137 CRELD1 Arina Puzriakova Tag Q4_24_NHS_review was removed from gene: CRELD1.
Tag Q4_24_MOI was removed from gene: CRELD1.
Early onset or syndromic epilepsy v8.137 CELF4 Arina Puzriakova Tag dd_review was removed from gene: CELF4.
Tag Q2_25_ promote_green was removed from gene: CELF4.
Early onset or syndromic epilepsy v8.137 RYR3 Achchuthan Shanmugasundram edited their review of gene: RYR3: Added comment: Additional comments from reviewing GLHs: Insufficient evidence to prove a monogenic cause of epilepsy. Larger cohort size analysis required to conclusively prove this gene / variants in this gene could act as a susceptibility gene for idiopathic partial epilepsy.; Changed rating: AMBER
Early onset or syndromic epilepsy v8.137 CELF4 Achchuthan Shanmugasundram edited their review of gene: CELF4: Added comment: Additional comments from reviewing GLHs: gnomad data would make this difficult to classify variants (gnomADv4.1.0 pLI score). All ClinVar variants are VUS.; Changed rating: AMBER
Early onset or syndromic epilepsy v8.136 CDK5 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: CDK5.
Early onset or syndromic epilepsy v8.136 C12orf66 Arina Puzriakova Tag Q1_25_ promote_green was removed from gene: C12orf66.
Early onset or syndromic epilepsy v8.136 BRSK1 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: BRSK1.
Early onset or syndromic epilepsy v8.136 BRSK1 Arina Puzriakova Classified gene: BRSK1 as Green List (high evidence)
Early onset or syndromic epilepsy v8.136 BRSK1 Arina Puzriakova Gene: brsk1 has been classified as Green List (High Evidence).
Early onset or syndromic epilepsy v8.135 BRSK1 Arina Puzriakova Classified gene: BRSK1 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v8.135 BRSK1 Arina Puzriakova Gene: brsk1 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v8.134 WDR47 Achchuthan Shanmugasundram commented on gene: WDR47: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v8.134 UNC13A Achchuthan Shanmugasundram commented on gene: UNC13A: 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.
Early onset or syndromic epilepsy v8.134 UGGT1 Achchuthan Shanmugasundram commented on gene: UGGT1: 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.
Early onset or syndromic epilepsy v8.134 UBR5 Achchuthan Shanmugasundram commented on gene: UBR5: 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.
Early onset or syndromic epilepsy v8.134 TRPM7 Achchuthan Shanmugasundram reviewed gene: TRPM7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v8.134 TMEM167A Achchuthan Shanmugasundram reviewed gene: TMEM167A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v8.134 TARS2 Achchuthan Shanmugasundram reviewed gene: TARS2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v8.134 SPOUT1 Achchuthan Shanmugasundram reviewed gene: SPOUT1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v8.134 RYR3 Achchuthan Shanmugasundram commented on gene: RYR3
Early onset or syndromic epilepsy v8.134 RNU5B-1 Achchuthan Shanmugasundram edited their review of gene: RNU5B-1: Added comment: The rating of this gene has been updated to green and the mode of inheritance set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Early onset or syndromic epilepsy v8.134 RNU2-2P Achchuthan Shanmugasundram commented on gene: RNU2-2P: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v8.134 PPP2R5C Achchuthan Shanmugasundram reviewed gene: PPP2R5C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v8.134 PPP2R2B Achchuthan Shanmugasundram reviewed gene: PPP2R2B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v8.134 PPOX Achchuthan Shanmugasundram reviewed gene: PPOX: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v8.134 PNPLA8 Achchuthan Shanmugasundram reviewed gene: PNPLA8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v8.134 PABPC1 Achchuthan Shanmugasundram commented on gene: PABPC1: The mode of inheritance of this gene has been updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v8.134 NOTCH3 Achchuthan Shanmugasundram commented on gene: NOTCH3: 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.
Early onset or syndromic epilepsy v8.134 MT-TK Achchuthan Shanmugasundram reviewed gene: MT-TK: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v8.134 MARK2 Achchuthan Shanmugasundram commented on gene: MARK2: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v8.134 LSS Achchuthan Shanmugasundram commented on gene: LSS: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v8.134 LGI1 Achchuthan Shanmugasundram commented on gene: LGI1
Early onset or syndromic epilepsy v8.134 LAMC3 Achchuthan Shanmugasundram commented on gene: LAMC3: 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.
Early onset or syndromic epilepsy v8.134 KCND3 Achchuthan Shanmugasundram reviewed gene: KCND3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v8.134 INPP4A Achchuthan Shanmugasundram commented on gene: INPP4A: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v8.134 GTF3C3 Achchuthan Shanmugasundram reviewed gene: GTF3C3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v8.134 GLS Achchuthan Shanmugasundram commented on gene: GLS: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v8.134 FLVCR1 Achchuthan Shanmugasundram reviewed gene: FLVCR1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v8.134 EPB41L3 Achchuthan Shanmugasundram reviewed gene: EPB41L3: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v8.134 ELFN1 Achchuthan Shanmugasundram reviewed gene: ELFN1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v8.134 EEFSEC Achchuthan Shanmugasundram commented on gene: EEFSEC: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Early onset or syndromic epilepsy v8.134 CTSF Achchuthan Shanmugasundram reviewed gene: CTSF: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v8.134 CRNKL1 Achchuthan Shanmugasundram commented on gene: CRNKL1: 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.
Early onset or syndromic epilepsy v8.134 CRELD1 Achchuthan Shanmugasundram commented on gene: CRELD1
Early onset or syndromic epilepsy v8.134 CELF4 Achchuthan Shanmugasundram commented on gene: CELF4: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber.
Early onset or syndromic epilepsy v8.134 CDK5 Achchuthan Shanmugasundram reviewed gene: CDK5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v8.134 C12orf66 Achchuthan Shanmugasundram reviewed gene: C12orf66: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v8.134 BRSK1 Achchuthan Shanmugasundram reviewed gene: BRSK1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Early onset or syndromic epilepsy v8.134 WDR47 Arina Puzriakova Source NHS GMS was added to WDR47.
Source Expert Review Green was added to WDR47.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 UNC13A Arina Puzriakova Source NHS GMS was added to UNC13A.
Source Expert Review Green was added to UNC13A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 UGGT1 Arina Puzriakova Source NHS GMS was added to UGGT1.
Source Expert Review Green was added to UGGT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 UBR5 Arina Puzriakova Source NHS GMS was added to UBR5.
Source Expert Review Green was added to UBR5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 TRPM7 Arina Puzriakova Source NHS GMS was added to TRPM7.
Source Expert Review Green was added to TRPM7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 TMEM167A Arina Puzriakova Source NHS GMS was added to TMEM167A.
Source Expert Review Green was added to TMEM167A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 TARS2 Arina Puzriakova Source NHS GMS was added to TARS2.
Source Expert Review Green was added to TARS2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 SPOUT1 Arina Puzriakova Source NHS GMS was added to SPOUT1.
Source Expert Review Green was added to SPOUT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 RNU5B-1 Arina Puzriakova Source NHS GMS was added to RNU5B-1.
Source Expert Review Green was added to RNU5B-1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 RNU2-2P Arina Puzriakova Source NHS GMS was added to RNU2-2P.
Source Expert Review Green was added to RNU2-2P.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 PPP2R5C Arina Puzriakova Source NHS GMS was added to PPP2R5C.
Source Expert Review Green was added to PPP2R5C.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 PPP2R2B Arina Puzriakova Source NHS GMS was added to PPP2R2B.
Source Expert Review Green was added to PPP2R2B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 PPOX Arina Puzriakova Source NHS GMS was added to PPOX.
Source Expert Review Green was added to PPOX.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 PNPLA8 Arina Puzriakova Source NHS GMS was added to PNPLA8.
Source Expert Review Green was added to PNPLA8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 PABPC1 Arina Puzriakova Mode of inheritance for gene PABPC1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Early onset or syndromic epilepsy v8.134 NOTCH3 Arina Puzriakova Source NHS GMS was added to NOTCH3.
Source Expert Review Green was added to NOTCH3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 MT-TK Arina Puzriakova Source NHS GMS was added to MT-TK.
Source Expert Review Green was added to MT-TK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 MARK2 Arina Puzriakova Source Expert Review Green was added to MARK2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 LSS Arina Puzriakova Source Expert Review Green was added to LSS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 LGI1 Arina Puzriakova Mode of inheritance for gene LGI1 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
Early onset or syndromic epilepsy v8.134 LAMC3 Arina Puzriakova Source NHS GMS was added to LAMC3.
Source Expert Review Green was added to LAMC3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 KCND3 Arina Puzriakova Source NHS GMS was added to KCND3.
Source Expert Review Green was added to KCND3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 INPP4A Arina Puzriakova Source NHS GMS was added to INPP4A.
Source Expert Review Green was added to INPP4A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 GTF3C3 Arina Puzriakova Source NHS GMS was added to GTF3C3.
Source Expert Review Green was added to GTF3C3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 GLS Arina Puzriakova Source NHS GMS was added to GLS.
Source Expert Review Green was added to GLS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 FLVCR1 Arina Puzriakova Source NHS GMS was added to FLVCR1.
Source Expert Review Green was added to FLVCR1.
Rating Changed from Red List (low evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 EPB41L3 Arina Puzriakova Source NHS GMS was added to EPB41L3.
Source Expert Review Green was added to EPB41L3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 ELFN1 Arina Puzriakova Source NHS GMS was added to ELFN1.
Source Expert Review Green was added to ELFN1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 EEFSEC Arina Puzriakova Source NHS GMS was added to EEFSEC.
Source Expert Review Green was added to EEFSEC.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 CTSF Arina Puzriakova Source Expert Review Green was added to CTSF.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 CRNKL1 Arina Puzriakova Source NHS GMS was added to CRNKL1.
Source Expert Review Green was added to CRNKL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 CRELD1 Arina Puzriakova 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 BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy v8.134 CDK5 Arina Puzriakova Source NHS GMS was added to CDK5.
Source Expert Review Green was added to CDK5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 C12orf66 Arina Puzriakova Source NHS GMS was added to C12orf66.
Source Expert Review Green was added to C12orf66.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Early onset or syndromic epilepsy v8.134 BRSK1 Arina Puzriakova Source NHS GMS was added to BRSK1.
Source Expert Review Green was added to BRSK1.
Mode of inheritance for gene BRSK1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Distal myopathies v6.18 TIA1 Arina Puzriakova Tag Q3_25_MOI was removed from gene: TIA1.
Distal myopathies v6.18 NEB Arina Puzriakova Tag dd_review was removed from gene: NEB.
Tag Q3_25_MOI was removed from gene: NEB.
Distal myopathies v6.18 TIA1 Achchuthan Shanmugasundram commented on gene: TIA1
Distal myopathies v6.18 NEB Achchuthan Shanmugasundram commented on gene: NEB: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Distal myopathies v6.17 TIA1 Arina Puzriakova Source NHS GMS was added to TIA1.
Mode of inheritance for gene TIA1 was changed from BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Distal myopathies v6.17 NEB Arina Puzriakova Source NHS GMS was added to NEB.
Mode of inheritance for gene NEB was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Clefting v6.22 SIX5 Achchuthan Shanmugasundram Tag Q3_25_expert_review was removed from gene: SIX5.
Tag Q3_25_demote_red was removed from gene: SIX5.
Clefting v6.22 MED16 Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: MED16.
Clefting v6.22 CTGF Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: CTGF.
Clefting v6.22 SIX5 Achchuthan Shanmugasundram reviewed gene: SIX5: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Clefting v6.22 MED16 Achchuthan Shanmugasundram commented on gene: MED16: 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.
Clefting v6.22 CTGF Achchuthan Shanmugasundram reviewed gene: CTGF: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Clefting v6.21 SIX5 Achchuthan Shanmugasundram Source NHS GMS was added to SIX5.
Source Expert Review Red was added to SIX5.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Clefting v6.21 MED16 Achchuthan Shanmugasundram Source NHS GMS was added to MED16.
Source Expert Review Green was added to MED16.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Clefting v6.21 CTGF Achchuthan Shanmugasundram Source NHS GMS was added to CTGF.
Source Expert Review Green was added to CTGF.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v7.15 CACNB4 Achchuthan Shanmugasundram Tag Q3_25_MOI was removed from gene: CACNB4.
Tag Q3_25_expert_review was removed from gene: CACNB4.
Tag Q3_25_demote_red was removed from gene: CACNB4.
Childhood onset dystonia, chorea or related movement disorder v7.15 TNR Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: TNR.
Childhood onset dystonia, chorea or related movement disorder v7.15 PDE1B Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: PDE1B.
Childhood onset dystonia, chorea or related movement disorder v7.15 ADCY5 Achchuthan Shanmugasundram Tag Q3_25_MOI was removed from gene: ADCY5.
Cystic kidney disease v8.8 CYP24A1 Arina Puzriakova Publications for gene: CYP24A1 were set to 34307984; 22337913; 27105398; 28324001
Childhood onset dystonia, chorea or related movement disorder v7.15 SPR Achchuthan Shanmugasundram Tag Q1_25_ MOI was removed from gene: SPR.
Tag watchlist_moi was removed from gene: SPR.
Cystic kidney disease v8.7 CYP24A1 Arina Puzriakova Tag Q1_26_MOI was removed from gene: CYP24A1.
Childhood onset dystonia, chorea or related movement disorder v7.15 TNR Achchuthan Shanmugasundram reviewed gene: TNR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Childhood onset dystonia, chorea or related movement disorder v7.15 SPR Achchuthan Shanmugasundram commented on gene: SPR
Childhood onset dystonia, chorea or related movement disorder v7.15 PDE1B Achchuthan Shanmugasundram commented on gene: PDE1B: The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v7.15 CACNB4 Achchuthan Shanmugasundram commented on gene: CACNB4: The rating of this gene has been updated to red and the mode of inheritance updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Childhood onset dystonia, chorea or related movement disorder v7.15 ADCY5 Achchuthan Shanmugasundram commented on gene: ADCY5: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Cystic kidney disease v8.7 CFAP47 Arina Puzriakova Tag Q4_24_promote_green was removed from gene: CFAP47.
Childhood onset dystonia, chorea or related movement disorder v7.14 TNR Achchuthan Shanmugasundram Source NHS GMS was added to TNR.
Source Expert Review Green was added to TNR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v7.14 SPR Achchuthan Shanmugasundram Source NHS GMS was added to SPR.
Mode of inheritance for gene SPR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v7.14 PDE1B Achchuthan Shanmugasundram Source NHS GMS was added to PDE1B.
Source Expert Review Green was added to PDE1B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v7.14 CACNB4 Achchuthan Shanmugasundram Source Expert Review Red was added to CACNB4.
Mode of inheritance for gene CACNB4 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rating Changed from Green List (high evidence) to Red List (low evidence)
Childhood onset dystonia, chorea or related movement disorder v7.14 ADCY5 Achchuthan Shanmugasundram Source NHS GMS was added to ADCY5.
Mode of inheritance for gene ADCY5 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cystic kidney disease v8.7 CYP24A1 Achchuthan Shanmugasundram reviewed gene: CYP24A1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Cystic kidney disease v8.7 CFAP47 Achchuthan Shanmugasundram commented on gene: CFAP47: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Cystic kidney disease v8.6 CYP24A1 Arina Puzriakova Mode of inheritance for gene CYP24A1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BIALLELIC, autosomal or pseudoautosomal
Cystic kidney disease v8.6 CFAP47 Arina Puzriakova Source NHS GMS was added to CFAP47.
Source Expert Review Green was added to CFAP47.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Cardiac arrhythmias - additional genes v3.9 TANGO2 Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: TANGO2.
Tag Q3_25_expert_review was removed from gene: TANGO2.
Cardiac arrhythmias - additional genes v3.9 TANGO2 Achchuthan Shanmugasundram changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. The GMS reviewers note as follows: TANGO2 causes an AR multi-system metabolic disorder, of which cardiac arrhythmia is not the presenting phenotype. It can be a feature when patients are in metabolic crisis. It is not appropriate to include genes associated with multi-system/syndromic disorders where cardiac arrhythmia may be a feature. TANGO2 is more appropriate for the panels it is already on.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber.

The GMS reviewers note as follows:
TANGO2 causes an AR multi-system metabolic disorder, of which cardiac arrhythmia is not the presenting phenotype. It can be a feature when patients are in metabolic crisis. It is not appropriate to include genes associated with multi-system/syndromic disorders where cardiac arrhythmia may be a feature. TANGO2 is more appropriate for the panels it is already on.
Cardiac arrhythmias - additional genes v3.9 TANGO2 Achchuthan Shanmugasundram edited their review of gene: TANGO2: Changed rating: AMBER
Cardiac arrhythmias - additional genes v3.9 TANGO2 Achchuthan Shanmugasundram commented on gene: TANGO2: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. The GMS reviewers note as follows: TANGO2 causes an AR multi-system metabolic disorder, of which cardiac arrhythmia is not the presenting phenotype. It can be a feature when patients are in metabolic crisis. It is not appropriate to include genes associated with multi-system/syndromic disorders where cardiac arrhythmia may be a feature. TANGO2 is more appropriate for the panels it is already on.
Paediatric or syndromic cardiomyopathy v7.98 MT-TV Ida Ertmanska Tag Q2_25_ promote_green was removed from gene: MT-TV.
Tag Q2_25_expert_review was removed from gene: MT-TV.
Paediatric or syndromic cardiomyopathy v7.98 MT-TL1 Ida Ertmanska Tag Q2_25_ promote_green was removed from gene: MT-TL1.
Tag Q2_25_expert_review was removed from gene: MT-TL1.
Paediatric or syndromic cardiomyopathy v7.98 TANGO2 Ida Ertmanska Tag Q3_25_promote_green was removed from gene: TANGO2.
Paediatric or syndromic cardiomyopathy v7.98 SGCG Ida Ertmanska Tag Q3_25_promote_green was removed from gene: SGCG.
Paediatric or syndromic cardiomyopathy v7.98 RPL3L Ida Ertmanska Tag Q3_25_promote_green was removed from gene: RPL3L.
Tag Q3_25_expert_review was removed from gene: RPL3L.
Tag Q3_25_NHS_review was removed from gene: RPL3L.
Paediatric or syndromic cardiomyopathy v7.98 PKD2 Ida Ertmanska Tag Q3_25_promote_green was removed from gene: PKD2.
Paediatric or syndromic cardiomyopathy v7.98 NF1 Ida Ertmanska Tag Q3_25_promote_green was removed from gene: NF1.
Paediatric or syndromic cardiomyopathy v7.98 NAXD Ida Ertmanska Tag Q3_25_promote_green was removed from gene: NAXD.
Paediatric or syndromic cardiomyopathy v7.98 MTO1 Ida Ertmanska Tag Q3_25_promote_green was removed from gene: MTO1.
Congenital disorders of glycosylation v7.15 MAN2B2 Arina Puzriakova Tag Q2_25_ promote_green was removed from gene: MAN2B2.
Tag Q2_25_ NHS_review was removed from gene: MAN2B2.
Paediatric or syndromic cardiomyopathy v7.98 KLHL24 Ida Ertmanska Tag Q3_25_promote_green was removed from gene: KLHL24.
Congenital disorders of glycosylation v7.15 UGGT1 Arina Puzriakova Tag Q3_25_promote_green was removed from gene: UGGT1.
Tag Q3_25_NHS_review was removed from gene: UGGT1.
Paediatric or syndromic cardiomyopathy v7.98 GLA Ida Ertmanska Tag Q3_25_promote_green was removed from gene: GLA.
Paediatric or syndromic cardiomyopathy v7.98 FLII Ida Ertmanska Tag Q3_25_promote_green was removed from gene: FLII.
Paediatric or syndromic cardiomyopathy v7.98 FBXL4 Ida Ertmanska Tag Q3_25_promote_green was removed from gene: FBXL4.
Paediatric or syndromic cardiomyopathy v7.98 DST Ida Ertmanska Tag Q3_25_promote_green was removed from gene: DST.
Paediatric or syndromic cardiomyopathy v7.98 ATAD3A Ida Ertmanska Tag Q3_25_promote_green was removed from gene: ATAD3A.
Paediatric or syndromic cardiomyopathy v7.98 AIFM1 Ida Ertmanska Tag Q3_25_promote_green was removed from gene: AIFM1.
Breast cancer pertinent cancer susceptibility v2.17 PTEN Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: PTEN.
Tag Q2_25_expert_review was removed from gene: PTEN.
Paediatric or syndromic cardiomyopathy v7.98 ADSSL1 Ida Ertmanska Tag Q3_25_promote_green was removed from gene: ADSSL1.
Breast cancer pertinent cancer susceptibility v2.17 PTEN Achchuthan Shanmugasundram changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains red. The GMS reviewers note that there are no clinical guidelines to manage the findings.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. The GMS reviewers note that there are no clinical guidelines to manage the findings.
Breast cancer pertinent cancer susceptibility v2.17 PTEN Achchuthan Shanmugasundram commented on gene: PTEN
Paediatric or syndromic cardiomyopathy v7.98 MT-ND5 Ida Ertmanska Tag Q2_25_ promote_green was removed from gene: MT-ND5.
Tag Q3_25_expert_review was removed from gene: MT-ND5.
Tag Q3_25_NHS_review was removed from gene: MT-ND5.
Paediatric or syndromic cardiomyopathy v7.98 TANGO2 Ida Ertmanska reviewed gene: TANGO2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric or syndromic cardiomyopathy v7.98 SGCG Ida Ertmanska reviewed gene: SGCG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric or syndromic cardiomyopathy v7.98 RPL3L Ida Ertmanska reviewed gene: RPL3L: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric or syndromic cardiomyopathy v7.98 PKD2 Ida Ertmanska reviewed gene: PKD2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric or syndromic cardiomyopathy v7.98 NF1 Ida Ertmanska reviewed gene: NF1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric or syndromic cardiomyopathy v7.98 NAXD Ida Ertmanska reviewed gene: NAXD: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric or syndromic cardiomyopathy v7.98 MTO1 Ida Ertmanska reviewed gene: MTO1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric or syndromic cardiomyopathy v7.98 MT-TV Ida Ertmanska commented on gene: MT-TV
Paediatric or syndromic cardiomyopathy v7.98 MT-TL1 Ida Ertmanska commented on gene: MT-TL1
Paediatric or syndromic cardiomyopathy v7.98 MT-ND5 Ida Ertmanska commented on gene: MT-ND5
Paediatric or syndromic cardiomyopathy v7.98 KLHL24 Ida Ertmanska reviewed gene: KLHL24: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric or syndromic cardiomyopathy v7.98 GLA Ida Ertmanska reviewed gene: GLA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric or syndromic cardiomyopathy v7.98 FLII Ida Ertmanska reviewed gene: FLII: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric or syndromic cardiomyopathy v7.98 FBXL4 Ida Ertmanska reviewed gene: FBXL4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric or syndromic cardiomyopathy v7.98 DST Ida Ertmanska reviewed gene: DST: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric or syndromic cardiomyopathy v7.98 ATAD3A Ida Ertmanska reviewed gene: ATAD3A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric or syndromic cardiomyopathy v7.98 AIFM1 Ida Ertmanska reviewed gene: AIFM1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric or syndromic cardiomyopathy v7.98 ADSSL1 Ida Ertmanska reviewed gene: ADSSL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Proteinuric renal disease v5.9 VIPAS39 Ida Ertmanska Tag Q1_25_ promote_green was removed from gene: VIPAS39.
Proteinuric renal disease v5.9 CD2AP Ida Ertmanska Tag Q3_25_promote_green was removed from gene: CD2AP.
Proteinuric renal disease v5.9 VIPAS39 Ida Ertmanska reviewed gene: VIPAS39: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Proteinuric renal disease v5.9 CD2AP Ida Ertmanska commented on gene: CD2AP: The rating of this gene has been updated to green and the mode of inheritance updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Bilateral congenital or childhood onset cataracts v7.8 HMBS Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: HMBS.
Proteinuric renal disease v5.8 VIPAS39 Ida Ertmanska Source Expert Review Green was added to VIPAS39.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Proteinuric renal disease v5.8 CD2AP Ida Ertmanska Source Expert Review Green was added to CD2AP.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Bilateral congenital or childhood onset cataracts v7.8 HMBS Achchuthan Shanmugasundram reviewed gene: HMBS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary immunodeficiency or monogenic inflammatory bowel disease v8.82 INO80 Ida Ertmanska Tag Q3_25_expert_review was removed from gene: INO80.
Tag Q3_25_demote_red was removed from gene: INO80.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.82 TMEFF1 Ida Ertmanska Tag Q3_25_promote_green was removed from gene: TMEFF1.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.82 TBK1 Ida Ertmanska Tag Q2_25_ MOI was removed from gene: TBK1.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.82 SLCO2A1 Ida Ertmanska Tag Q2_25_ MOI was removed from gene: SLCO2A1.
Bilateral congenital or childhood onset cataracts v7.7 HMBS Achchuthan Shanmugasundram Source NHS GMS was added to HMBS.
Source Expert Review Green was added to HMBS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v8.67 EXOSC5 Achchuthan Shanmugasundram Tag Q4_24_NHS_review was removed from gene: EXOSC5.
Tag Q4_24_promote_green was removed from gene: EXOSC5.
Ataxia and cerebellar anomalies - narrow panel v8.67 PTRH2 Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: PTRH2.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.82 SLC39A4 Ida Ertmanska Tag Q3_25_promote_green was removed from gene: SLC39A4.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.82 IRF1 Ida Ertmanska Tag Q3_25_promote_green was removed from gene: IRF1.
Tag Q3_25_NHS_review was removed from gene: IRF1.
Ataxia and cerebellar anomalies - narrow panel v8.67 PDE1B Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: PDE1B.
Tag Q3_25_NHS_review was removed from gene: PDE1B.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.82 IFNAR1 Ida Ertmanska Tag Q3_25_promote_green was removed from gene: IFNAR1.
Ataxia and cerebellar anomalies - narrow panel v8.67 INPP4A Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: INPP4A.
Ataxia and cerebellar anomalies - narrow panel v8.67 HEATR5B Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: HEATR5B.
Tag Q3_25_expert_review was removed from gene: HEATR5B.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.82 SLC30A2 Ida Ertmanska Tag Q3_25_promote_green was removed from gene: SLC30A2.
Tag Q3_25_MOI was removed from gene: SLC30A2.
Tag Q3_25_expert_review was removed from gene: SLC30A2.
Ataxia and cerebellar anomalies - narrow panel v8.67 EXOSC8 Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: EXOSC8.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.82 TMEFF1 Ida Ertmanska reviewed gene: TMEFF1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary immunodeficiency or monogenic inflammatory bowel disease v8.82 TBK1 Ida Ertmanska commented on gene: TBK1
Primary immunodeficiency or monogenic inflammatory bowel disease v8.82 SLCO2A1 Ida Ertmanska commented on gene: SLCO2A1
Primary immunodeficiency or monogenic inflammatory bowel disease v8.82 SLC39A4 Ida Ertmanska reviewed gene: SLC39A4: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary immunodeficiency or monogenic inflammatory bowel disease v8.82 SLC30A2 Ida Ertmanska commented on gene: SLC30A2
Primary immunodeficiency or monogenic inflammatory bowel disease v8.82 IRF1 Ida Ertmanska reviewed gene: IRF1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary immunodeficiency or monogenic inflammatory bowel disease v8.82 INO80 Ida Ertmanska reviewed gene: INO80: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary immunodeficiency or monogenic inflammatory bowel disease v8.82 IFNAR1 Ida Ertmanska reviewed gene: IFNAR1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary immunodeficiency or monogenic inflammatory bowel disease v8.82 HSPA1L Ida Ertmanska reviewed gene: HSPA1L: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary immunodeficiency or monogenic inflammatory bowel disease v8.82 ELF4 Ida Ertmanska commented on gene: ELF4
Primary immunodeficiency or monogenic inflammatory bowel disease v8.82 DPP9 Ida Ertmanska reviewed gene: DPP9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary immunodeficiency or monogenic inflammatory bowel disease v8.82 C2 Ida Ertmanska commented on gene: C2
Ataxia and cerebellar anomalies - narrow panel v8.67 CRNKL1 Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: CRNKL1.
Ataxia and cerebellar anomalies - narrow panel v8.67 CDK5 Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: CDK5.
Ataxia and cerebellar anomalies - narrow panel v8.67 RAB3A Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: RAB3A.
Tag Q2_25_ NHS_review was removed from gene: RAB3A.
Ataxia and cerebellar anomalies - narrow panel v8.67 NEU1 Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: NEU1.
Tag Q2_25_ NHS_review was removed from gene: NEU1.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.81 ELF4 Ida Ertmanska Tag Q2_25_ MOI was removed from gene: ELF4.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.81 DPP9 Ida Ertmanska Tag Q3_25_promote_green was removed from gene: DPP9.
Tag Q3_25_NHS_review was removed from gene: DPP9.
Ataxia and cerebellar anomalies - narrow panel v8.67 MFSD8 Achchuthan Shanmugasundram Tag Q1_25_ promote_green was removed from gene: MFSD8.
Ataxia and cerebellar anomalies - narrow panel v8.67 FTH1 Achchuthan Shanmugasundram Tag Q1_25_ NHS_review was removed from gene: FTH1.
Tag Q1_25_ promote_green was removed from gene: FTH1.
Ataxia and cerebellar anomalies - narrow panel v8.67 EEFSEC Achchuthan Shanmugasundram Tag Q1_25_ promote_green was removed from gene: EEFSEC.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.81 C2 Ida Ertmanska Tag Q2_25_ MOI was removed from gene: C2.
Ataxia and cerebellar anomalies - narrow panel v8.67 RAB3A Achchuthan Shanmugasundram reviewed gene: RAB3A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v8.67 PTRH2 Achchuthan Shanmugasundram commented on gene: PTRH2: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Ataxia and cerebellar anomalies - narrow panel v8.67 PDE1B Achchuthan Shanmugasundram commented on gene: PDE1B: 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.
Ataxia and cerebellar anomalies - narrow panel v8.67 NEU1 Achchuthan Shanmugasundram reviewed gene: NEU1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v8.67 MFSD8 Achchuthan Shanmugasundram reviewed gene: MFSD8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v8.67 INPP4A Achchuthan Shanmugasundram commented on gene: INPP4A: 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.
Ataxia and cerebellar anomalies - narrow panel v8.67 HEATR5B Achchuthan Shanmugasundram reviewed gene: HEATR5B: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v8.67 FTH1 Achchuthan Shanmugasundram reviewed gene: FTH1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v8.67 EXOSC8 Achchuthan Shanmugasundram reviewed gene: EXOSC8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v8.67 EXOSC5 Achchuthan Shanmugasundram reviewed gene: EXOSC5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ataxia and cerebellar anomalies - narrow panel v8.67 EEFSEC Achchuthan Shanmugasundram commented on gene: EEFSEC: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Ataxia and cerebellar anomalies - narrow panel v8.67 CRNKL1 Achchuthan Shanmugasundram commented on gene: CRNKL1: 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.
Ataxia and cerebellar anomalies - narrow panel v8.67 CDK5 Achchuthan Shanmugasundram reviewed gene: CDK5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Primary immunodeficiency or monogenic inflammatory bowel disease v8.81 HSPA1L Ida Ertmanska Tag Q3_25_expert_review was removed from gene: HSPA1L.
Tag Q3_25_demote_amber was removed from gene: HSPA1L.
Ataxia and cerebellar anomalies - narrow panel v8.66 CACNA1A_CAG Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from STR: CACNA1A_CAG.
Tag Q2_25_expert_review was removed from STR: CACNA1A_CAG.
Ataxia and cerebellar anomalies - narrow panel v8.66 CACNA1A_CAG Achchuthan Shanmugasundram reviewed STR: CACNA1A_CAG: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v8.66 ATXN10_ATTCT Achchuthan Shanmugasundram reviewed STR: ATXN10_ATTCT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Ataxia and cerebellar anomalies - narrow panel v8.66 ATXN10_ATTCT Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from STR: ATXN10_ATTCT.
Tag Q2_25_expert_review was removed from STR: ATXN10_ATTCT.
Ataxia and cerebellar anomalies - narrow panel v8.66 ATXN10_ATTCT Achchuthan Shanmugasundram Classified STR: ATXN10_ATTCT as Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v8.66 ATXN10_ATTCT Achchuthan Shanmugasundram Str: atxn10_attct has been classified as Green List (High Evidence).
Ataxia and cerebellar anomalies - narrow panel v8.65 RAB3A Achchuthan Shanmugasundram Source NHS GMS was added to RAB3A.
Source Expert Review Green was added to RAB3A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v8.65 PTRH2 Achchuthan Shanmugasundram Source NHS GMS was added to PTRH2.
Source Expert Review Green was added to PTRH2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v8.65 PDE1B Achchuthan Shanmugasundram Source NHS GMS was added to PDE1B.
Source Expert Review Green was added to PDE1B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v8.65 NEU1 Achchuthan Shanmugasundram Source Expert Review Green was added to NEU1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v8.65 MFSD8 Achchuthan Shanmugasundram Source Expert Review Green was added to MFSD8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v8.65 INPP4A Achchuthan Shanmugasundram Source NHS GMS was added to INPP4A.
Source Expert Review Green was added to INPP4A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v8.65 HEATR5B Achchuthan Shanmugasundram Source NHS GMS was added to HEATR5B.
Source Expert Review Green was added to HEATR5B.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v8.65 FTH1 Achchuthan Shanmugasundram Source Expert Review Green was added to FTH1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v8.65 EXOSC8 Achchuthan Shanmugasundram Source NHS GMS was added to EXOSC8.
Source Expert Review Green was added to EXOSC8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v8.65 EXOSC5 Achchuthan Shanmugasundram Source NHS GMS was added to EXOSC5.
Source Expert Review Green was added to EXOSC5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v8.65 EEFSEC Achchuthan Shanmugasundram Source NHS GMS was added to EEFSEC.
Source Expert Review Green was added to EEFSEC.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v8.65 CRNKL1 Achchuthan Shanmugasundram Source NHS GMS was added to CRNKL1.
Source Expert Review Green was added to CRNKL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ataxia and cerebellar anomalies - narrow panel v8.65 CDK5 Achchuthan Shanmugasundram Source NHS GMS was added to CDK5.
Source Expert Review Green was added to CDK5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v8.81 TMEFF1 Ida Ertmanska Source NHS GMS was added to TMEFF1.
Source Expert Review Green was added to TMEFF1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v8.81 TBK1 Ida Ertmanska Mode of inheritance for gene TBK1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v8.81 SLCO2A1 Ida Ertmanska Source NHS GMS was added to SLCO2A1.
Mode of inheritance for gene SLCO2A1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease v8.81 SLC39A4 Ida Ertmanska Source Expert Review Green was added to SLC39A4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v8.81 IRF1 Ida Ertmanska Source NHS GMS was added to IRF1.
Source Expert Review Green was added to IRF1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v8.81 INO80 Ida Ertmanska Source Expert Review Red was added to INO80.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v8.81 IFNAR1 Ida Ertmanska Source NHS GMS was added to IFNAR1.
Source Expert Review Green was added to IFNAR1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v8.81 HSPA1L Ida Ertmanska Source Expert Review Amber was added to HSPA1L.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v8.81 ELF4 Ida Ertmanska Source NHS GMS was added to ELF4.
Mode of inheritance for gene ELF4 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)
Primary immunodeficiency or monogenic inflammatory bowel disease v8.81 DPP9 Ida Ertmanska Source NHS GMS was added to DPP9.
Source Expert Review Green was added to DPP9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v8.81 C2 Ida Ertmanska Mode of inheritance for gene C2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Paediatric or syndromic cardiomyopathy v7.97 TANGO2 Ida Ertmanska Source NHS GMS was added to TANGO2.
Source Expert Review Green was added to TANGO2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v7.97 SGCG Ida Ertmanska Source NHS GMS was added to SGCG.
Source Expert Review Green was added to SGCG.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v7.97 RPL3L Ida Ertmanska Source NHS GMS was added to RPL3L.
Source Expert Review Green was added to RPL3L.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v7.97 PKD2 Ida Ertmanska Source NHS GMS was added to PKD2.
Source Expert Review Green was added to PKD2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v7.97 NF1 Ida Ertmanska Source Expert Review Green was added to NF1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v7.97 NAXD Ida Ertmanska Source NHS GMS was added to NAXD.
Source Expert Review Green was added to NAXD.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v7.97 MTO1 Ida Ertmanska Source NHS GMS was added to MTO1.
Source Expert Review Green was added to MTO1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v7.97 KLHL24 Ida Ertmanska Source NHS GMS was added to KLHL24.
Source Expert Review Green was added to KLHL24.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v7.97 GLA Ida Ertmanska Source Expert Review Green was added to GLA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v7.97 FLII Ida Ertmanska Source NHS GMS was added to FLII.
Source Expert Review Green was added to FLII.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v7.97 FBXL4 Ida Ertmanska Source NHS GMS was added to FBXL4.
Source Expert Review Green was added to FBXL4.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v7.97 DST Ida Ertmanska Source NHS GMS was added to DST.
Source Expert Review Green was added to DST.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v7.97 ATAD3A Ida Ertmanska Source NHS GMS was added to ATAD3A.
Source Expert Review Green was added to ATAD3A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v7.97 AIFM1 Ida Ertmanska Source NHS GMS was added to AIFM1.
Source Expert Review Green was added to AIFM1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric or syndromic cardiomyopathy v7.97 ADSSL1 Ida Ertmanska Source NHS GMS was added to ADSSL1.
Source Expert Review Green was added to ADSSL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v7.33 IGFALS Ida Ertmanska Tag Q2_25_ promote_green was removed from gene: IGFALS.
Tag Q2_25_ NHS_review was removed from gene: IGFALS.
Paediatric disorders - additional genes v7.33 PLD1 Ida Ertmanska Tag Q3_25_promote_green was removed from gene: PLD1.
Tag Q3_25_expert_review was removed from gene: PLD1.
Paediatric disorders - additional genes v7.33 RBFOX2 Ida Ertmanska Tag Q3_25_promote_green was removed from gene: RBFOX2.
Paediatric disorders - additional genes v7.33 PLAG1 Ida Ertmanska Tag Q1_25_ NHS_review was removed from gene: PLAG1.
Tag Q1_25_ promote_green was removed from gene: PLAG1.
Paediatric disorders - additional genes v7.33 MC4R Ida Ertmanska Tag Q3_25_promote_green was removed from gene: MC4R.
Tag Q3_25_NHS_review was removed from gene: MC4R.
Paediatric disorders - additional genes v7.33 ISL1 Ida Ertmanska Tag Q3_25_promote_green was removed from gene: ISL1.
Paediatric disorders - additional genes v7.33 HMGA2 Ida Ertmanska Tag Q1_25_ NHS_review was removed from gene: HMGA2.
Tag Q1_25_ promote_green was removed from gene: HMGA2.
Paediatric disorders - additional genes v7.33 GPKOW Ida Ertmanska Tag Q3_25_promote_green was removed from gene: GPKOW.
Retinal disorders v8.97 PAX6 Eleanor Williams commented on gene: PAX6
Retinal disorders v8.97 FRMD7 Eleanor Williams commented on gene: FRMD7
Retinal disorders v8.97 VSX2 Eleanor Williams reviewed gene: VSX2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v8.97 THRB Eleanor Williams reviewed gene: THRB: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v8.97 SPG11 Eleanor Williams reviewed gene: SPG11: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v8.97 POC5 Eleanor Williams reviewed gene: POC5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v8.97 IDH3G Eleanor Williams reviewed gene: IDH3G: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v8.97 DHX38 Eleanor Williams reviewed gene: DHX38: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v8.97 C19orf44 Eleanor Williams reviewed gene: C19orf44: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v8.97 AP5Z1 Eleanor Williams reviewed gene: AP5Z1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v8.97 AP5M1 Eleanor Williams reviewed gene: AP5M1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v8.97 DYRK1A Eleanor Williams reviewed gene: DYRK1A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v8.97 RNU6-9 Eleanor Williams reviewed gene: RNU6-9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v8.97 RNU6-8 Eleanor Williams reviewed gene: RNU6-8: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v8.97 RNU6-2 Eleanor Williams reviewed gene: RNU6-2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v8.97 RNU6-1 Eleanor Williams reviewed gene: RNU6-1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v8.97 RNU4-2 Eleanor Williams reviewed gene: RNU4-2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v8.97 TBC1D32 Eleanor Williams reviewed gene: TBC1D32: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v8.97 CYP2U1 Eleanor Williams reviewed gene: CYP2U1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v8.97 UNC119 Eleanor Williams reviewed gene: UNC119: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Retinal disorders v8.97 SAG Eleanor Williams commented on gene: SAG
Retinal disorders v8.97 RLBP1 Eleanor Williams commented on gene: RLBP1
Retinal disorders v8.97 RDH5 Eleanor Williams commented on gene: RDH5: The mode of inheritance of this gene has been updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Retinal disorders v8.97 KIAA1549 Eleanor Williams commented on gene: KIAA1549
Retinal disorders v8.96 VSX2 Eleanor Williams Source Expert Review Green was added to VSX2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v8.96 UNC119 Eleanor Williams Source Expert Review Amber was added to UNC119.
Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Retinal disorders v8.96 THRB Eleanor Williams Source NHS GMS was added to THRB.
Source Expert Review Green was added to THRB.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v8.96 TBC1D32 Eleanor Williams Source NHS GMS was added to TBC1D32.
Source Expert Review Green was added to TBC1D32.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v8.96 SPG11 Eleanor Williams Source NHS GMS was added to SPG11.
Source Expert Review Green was added to SPG11.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v8.96 SAG Eleanor Williams Mode of inheritance for gene SAG was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Retinal disorders v8.96 RNU6-9 Eleanor Williams Source NHS GMS was added to RNU6-9.
Source Expert Review Green was added to RNU6-9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v8.96 RNU6-8 Eleanor Williams Source NHS GMS was added to RNU6-8.
Source Expert Review Green was added to RNU6-8.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v8.96 RNU6-2 Eleanor Williams Source NHS GMS was added to RNU6-2.
Source Expert Review Green was added to RNU6-2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v8.96 RNU6-1 Eleanor Williams Source NHS GMS was added to RNU6-1.
Source Expert Review Green was added to RNU6-1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v8.96 RNU4-2 Eleanor Williams Source NHS GMS was added to RNU4-2.
Source Expert Review Green was added to RNU4-2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v8.96 RLBP1 Eleanor Williams Mode of inheritance for gene RLBP1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v8.96 RDH5 Eleanor Williams Mode of inheritance for gene RDH5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v8.96 POC5 Eleanor Williams Source Expert Review Green was added to POC5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v8.96 KIAA1549 Eleanor Williams Mode of inheritance for gene KIAA1549 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Retinal disorders v8.96 IDH3G Eleanor Williams Source NHS GMS was added to IDH3G.
Source Expert Review Green was added to IDH3G.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v8.96 DYRK1A Eleanor Williams Source NHS GMS was added to DYRK1A.
Source Expert Review Green was added to DYRK1A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v8.96 DHX38 Eleanor Williams Source Expert Review Green was added to DHX38.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v8.96 CYP2U1 Eleanor Williams Source NHS GMS was added to CYP2U1.
Source Expert Review Green was added to CYP2U1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v8.96 C19orf44 Eleanor Williams Source NHS GMS was added to C19orf44.
Source Expert Review Green was added to C19orf44.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v8.96 AP5Z1 Eleanor Williams Source NHS GMS was added to AP5Z1.
Source Expert Review Green was added to AP5Z1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Retinal disorders v8.96 AP5M1 Eleanor Williams Source NHS GMS was added to AP5M1.
Source Expert Review Green was added to AP5M1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v7.33 ERCC1 Ida Ertmanska Tag Q3_25_promote_green was removed from gene: ERCC1.
Paediatric disorders - additional genes v7.33 CACHD1 Ida Ertmanska Tag Q1_25_ promote_green was removed from gene: CACHD1.
Paediatric disorders - additional genes v7.33 RBFOX2 Ida Ertmanska reviewed gene: RBFOX2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric disorders - additional genes v7.33 PLD1 Ida Ertmanska reviewed gene: PLD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric disorders - additional genes v7.33 PLAG1 Ida Ertmanska reviewed gene: PLAG1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric disorders - additional genes v7.33 MC4R Ida Ertmanska reviewed gene: MC4R: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric disorders - additional genes v7.33 ISL1 Ida Ertmanska reviewed gene: ISL1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric disorders - additional genes v7.33 IGFALS Ida Ertmanska reviewed gene: IGFALS: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric disorders - additional genes v7.33 HMGA2 Ida Ertmanska reviewed gene: HMGA2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric disorders - additional genes v7.33 GPKOW Ida Ertmanska reviewed gene: GPKOW: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric disorders - additional genes v7.33 ERCC1 Ida Ertmanska reviewed gene: ERCC1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric disorders - additional genes v7.33 CACHD1 Ida Ertmanska reviewed gene: CACHD1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Paediatric disorders - additional genes v7.32 RBFOX2 Ida Ertmanska Source NHS GMS was added to RBFOX2.
Source Expert Review Green was added to RBFOX2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v7.32 PLD1 Ida Ertmanska Source Expert Review Green was added to PLD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v7.32 PLAG1 Ida Ertmanska Source Expert Review Green was added to PLAG1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v7.32 MC4R Ida Ertmanska Source NHS GMS was added to MC4R.
Source Expert Review Green was added to MC4R.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v7.32 ISL1 Ida Ertmanska Source NHS GMS was added to ISL1.
Source Expert Review Green was added to ISL1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v7.32 IGFALS Ida Ertmanska Source Expert Review Green was added to IGFALS.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v7.32 HMGA2 Ida Ertmanska Source Expert Review Green was added to HMGA2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v7.32 GPKOW Ida Ertmanska Source NHS GMS was added to GPKOW.
Source Expert Review Green was added to GPKOW.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v7.32 ERCC1 Ida Ertmanska Source NHS GMS was added to ERCC1.
Source Expert Review Green was added to ERCC1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Paediatric disorders - additional genes v7.32 CACHD1 Ida Ertmanska Source NHS GMS was added to CACHD1.
Source Expert Review Green was added to CACHD1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ophthalmological ciliopathies v5.15 KIAA0556 Ida Ertmanska Tag Q3_25_promote_green was removed from gene: KIAA0556.
Ophthalmological ciliopathies v5.15 POC5 Ida Ertmanska Tag Q3_25_promote_green was removed from gene: POC5.
Ophthalmological ciliopathies v5.15 POC5 Ida Ertmanska reviewed gene: POC5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ophthalmological ciliopathies v5.15 KIAA0556 Ida Ertmanska reviewed gene: KIAA0556: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Ophthalmological ciliopathies v5.14 POC5 Ida Ertmanska Source Expert Review Green was added to POC5.
Source NHS GMS was added to POC5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Ophthalmological ciliopathies v5.14 KIAA0556 Ida Ertmanska Source Expert Review Green was added to KIAA0556.
Source NHS GMS was added to KIAA0556.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Congenital disorders of glycosylation v7.15 UGGT1 Achchuthan Shanmugasundram commented on gene: UGGT1: 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 disorders of glycosylation v7.15 MAN2B2 Achchuthan Shanmugasundram edited their review of gene: MAN2B2: Added comment: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.; Changed rating: GREEN
Congenital disorders of glycosylation v7.14 UGGT1 Arina Puzriakova Source Expert Review Green was added to UGGT1.
Source NHS GMS was added to UGGT1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Congenital disorders of glycosylation v7.14 MAN2B2 Arina Puzriakova Source Expert Review Green was added to MAN2B2.
Source NHS GMS was added to MAN2B2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Neurological ciliopathies v6.15 KIAA0556 Ida Ertmanska Tag Q3_25_promote_green was removed from gene: KIAA0556.
Neurological ciliopathies v6.15 EVC2 Ida Ertmanska Tag Q3_25_MOI was removed from gene: EVC2.
Arthrogryposis v9.29 MYH3 Achchuthan Shanmugasundram Tag Q3_25_MOI was removed from gene: MYH3.
Arthrogryposis v9.29 ERCC1 Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: ERCC1.
Arthrogryposis v9.29 DST Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: DST.
Arthrogryposis v9.29 MYH3 Achchuthan Shanmugasundram commented on gene: MYH3
Arthrogryposis v9.29 ERCC1 Achchuthan Shanmugasundram reviewed gene: ERCC1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Arthrogryposis v9.29 DST Achchuthan Shanmugasundram reviewed gene: DST: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Arthrogryposis v9.28 MYH3 Achchuthan Shanmugasundram Source NHS GMS was added to MYH3.
Mode of inheritance for gene MYH3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Arthrogryposis v9.28 ERCC1 Achchuthan Shanmugasundram Source NHS GMS was added to ERCC1.
Source Expert Review Green was added to ERCC1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Arthrogryposis v9.28 DST Achchuthan Shanmugasundram Source NHS GMS was added to DST.
Source Expert Review Green was added to DST.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset neurodegenerative disorder v8.16 SPTLC2 Achchuthan Shanmugasundram Mode of pathogenicity for gene: SPTLC2 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
Adult onset neurodegenerative disorder v8.15 SPTLC2 Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: SPTLC2.
Adult onset neurodegenerative disorder v8.15 SPTLC1 Achchuthan Shanmugasundram Tag Q3_25_promote_green was removed from gene: SPTLC1.
Tag Q3_25_NHS_review was removed from gene: SPTLC1.
Neurological ciliopathies v6.15 KIAA0556 Ida Ertmanska reviewed gene: KIAA0556: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Neurological ciliopathies v6.15 EVC2 Ida Ertmanska commented on gene: EVC2: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Adult onset neurodegenerative disorder v8.15 CST3 Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: CST3.
Adult onset neurodegenerative disorder v8.15 CST3 Achchuthan Shanmugasundram changed review comment from: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. The GMS reviewes note that the primary phenotype is leukodystrophy and there is insufficient information to support a monogenic cause of neurodegenerative disorder.; to: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. The GMS reviewers note that the primary phenotype is leukodystrophy and there is insufficient information to support a monogenic cause of neurodegenerative disorder.
Adult onset neurodegenerative disorder v8.15 CST3 Achchuthan Shanmugasundram edited their review of gene: CST3: Changed rating: AMBER
Neurological ciliopathies v6.14 KIAA0556 Ida Ertmanska Source NHS GMS was added to KIAA0556.
Source Expert Review Green was added to KIAA0556.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Neurological ciliopathies v6.14 EVC2 Ida Ertmanska Source NHS GMS was added to EVC2.
Mode of inheritance for gene EVC2 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder v8.15 POLG Achchuthan Shanmugasundram Tag Q1_25_ promote_green was removed from gene: POLG.
Neonatal diabetes v5.19 TMEM167A Ida Ertmanska Tag Q3_25_promote_green was removed from gene: TMEM167A.
Neonatal diabetes v5.19 TMEM167A Ida Ertmanska reviewed gene: TMEM167A: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Neonatal diabetes v5.18 TMEM167A Ida Ertmanska Source Expert Review Green was added to TMEM167A.
Source NHS GMS was added to TMEM167A.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v9.43 TOMM7 Ida Ertmanska Tag Q2_25_ promote_green was removed from gene: TOMM7.
Mitochondrial disorders v9.43 SUPV3L1 Ida Ertmanska Tag Q1_25_ promote_green was removed from gene: SUPV3L1.
Mitochondrial disorders v9.43 SQOR Ida Ertmanska Tag Q2_25_ promote_green was removed from gene: SQOR.
Mitochondrial disorders v9.43 PPOX Ida Ertmanska Tag Q3_25_MOI was removed from gene: PPOX.
Mitochondrial disorders v9.43 PDE12 Ida Ertmanska Tag Q3_25_promote_green was removed from gene: PDE12.
Tag Q3_25_NHS_review was removed from gene: PDE12.
Mitochondrial disorders v9.43 NDUFB7 Ida Ertmanska Tag Q1_25_ promote_green was removed from gene: NDUFB7.
Mitochondrial disorders v9.43 MRPL49 Ida Ertmanska Tag Q2_25_ promote_green was removed from gene: MRPL49.
Mitochondrial disorders v9.43 IDH1 Ida Ertmanska Tag Q2_25_ promote_green was removed from gene: IDH1.
Mitochondrial disorders v9.43 HSPA9 Ida Ertmanska Tag Q2_25_ promote_green was removed from gene: HSPA9.
Mitochondrial disorders v9.43 GUK1 Ida Ertmanska Tag Q3_25_promote_green was removed from gene: GUK1.
Tag Q3_25_NHS_review was removed from gene: GUK1.
Mitochondrial disorders v9.43 COX4I1 Ida Ertmanska Tag Q2_25_ promote_green was removed from gene: COX4I1.
Mitochondrial disorders v9.43 COX18 Ida Ertmanska Tag Q3_25_promote_green was removed from gene: COX18.
Mitochondrial disorders v9.43 CMPK2 Ida Ertmanska Tag Q2_25_ promote_green was removed from gene: CMPK2.
Mitochondrial disorders v9.43 TOMM7 Ida Ertmanska reviewed gene: TOMM7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Mitochondrial disorders v9.43 SUPV3L1 Ida Ertmanska reviewed gene: SUPV3L1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Mitochondrial disorders v9.43 SQOR Ida Ertmanska reviewed gene: SQOR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Mitochondrial disorders v9.43 PPOX Ida Ertmanska commented on gene: PPOX: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Mitochondrial disorders v9.43 PDE12 Ida Ertmanska reviewed gene: PDE12: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Mitochondrial disorders v9.43 NDUFB7 Ida Ertmanska reviewed gene: NDUFB7: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Mitochondrial disorders v9.43 MRPL49 Ida Ertmanska reviewed gene: MRPL49: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Mitochondrial disorders v9.43 IDH1 Ida Ertmanska reviewed gene: IDH1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Mitochondrial disorders v9.43 HSPA9 Ida Ertmanska reviewed gene: HSPA9: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Mitochondrial disorders v9.43 GUK1 Ida Ertmanska reviewed gene: GUK1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Mitochondrial disorders v9.43 COX4I1 Ida Ertmanska reviewed gene: COX4I1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Mitochondrial disorders v9.43 COX18 Ida Ertmanska reviewed gene: COX18: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Mitochondrial disorders v9.43 CMPK2 Ida Ertmanska reviewed gene: CMPK2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Mitochondrial disorders v9.43 BTD Ida Ertmanska reviewed gene: BTD: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Mitochondrial disorders v9.42 TOMM7 Ida Ertmanska Source NHS GMS was added to TOMM7.
Source Expert Review Green was added to TOMM7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v9.42 SUPV3L1 Ida Ertmanska Source NHS GMS was added to SUPV3L1.
Source Expert Review Green was added to SUPV3L1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v9.42 SQOR Ida Ertmanska Source NHS GMS was added to SQOR.
Source Expert Review Green was added to SQOR.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v9.42 PPOX Ida Ertmanska Mode of inheritance for gene PPOX was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Mitochondrial disorders v9.42 PDE12 Ida Ertmanska Source NHS GMS was added to PDE12.
Source Expert Review Green was added to PDE12.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v9.42 NDUFB7 Ida Ertmanska Source NHS GMS was added to NDUFB7.
Source Expert Review Green was added to NDUFB7.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v9.42 MRPL49 Ida Ertmanska Source NHS GMS was added to MRPL49.
Source Expert Review Green was added to MRPL49.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v9.42 IDH1 Ida Ertmanska Source NHS GMS was added to IDH1.
Source Expert Review Green was added to IDH1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v9.42 HSPA9 Ida Ertmanska Source NHS GMS was added to HSPA9.
Source Expert Review Green was added to HSPA9.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v9.42 GUK1 Ida Ertmanska Source NHS GMS was added to GUK1.
Source Expert Review Green was added to GUK1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v9.42 COX4I1 Ida Ertmanska Source NHS GMS was added to COX4I1.
Source Expert Review Green was added to COX4I1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v9.42 COX18 Ida Ertmanska Source Expert Review Green was added to COX18.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v9.42 CMPK2 Ida Ertmanska Source NHS GMS was added to CMPK2.
Source Expert Review Green was added to CMPK2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Mitochondrial disorders v9.42 BTD Ida Ertmanska Source Expert Review Green was added to BTD.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v7.36 CDK5 Ida Ertmanska Tag Q3_25_promote_green was removed from gene: CDK5.
Malformations of cortical development v7.36 NFIA Ida Ertmanska Tag Q3_25_promote_green was removed from gene: NFIA.
Malformations of cortical development v7.36 NFIA Ida Ertmanska reviewed gene: NFIA: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Malformations of cortical development v7.36 CDK5 Ida Ertmanska reviewed gene: CDK5: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Malformations of cortical development v7.35 NFIA Ida Ertmanska Source Expert Review Green was added to NFIA.
Source NHS GMS was added to NFIA.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Malformations of cortical development v7.35 CDK5 Ida Ertmanska Source Expert Review Green was added to CDK5.
Source NHS GMS was added to CDK5.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Limb disorders v7.22 FLVCR1 Ida Ertmanska Tag Q3_25_promote_green was removed from gene: FLVCR1.
Limb disorders v7.22 RPL26 Ida Ertmanska Tag Q2_25_ promote_green was removed from gene: RPL26.
Limb disorders v7.22 RPL26 Ida Ertmanska reviewed gene: RPL26: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Limb disorders v7.22 FLVCR1 Ida Ertmanska reviewed gene: FLVCR1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Limb disorders v7.21 RPL26 Ida Ertmanska Source NHS GMS was added to RPL26.
Source Expert Review Green was added to RPL26.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Limb disorders v7.21 FLVCR1 Ida Ertmanska Source NHS GMS was added to FLVCR1.
Source Expert Review Green was added to FLVCR1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset neurodegenerative disorder v8.15 SPTLC2 Achchuthan Shanmugasundram reviewed gene: SPTLC2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset neurodegenerative disorder v8.15 SPTLC1 Achchuthan Shanmugasundram reviewed gene: SPTLC1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset neurodegenerative disorder v8.15 POLG Achchuthan Shanmugasundram reviewed gene: POLG: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset neurodegenerative disorder v8.15 CST3 Achchuthan Shanmugasundram commented on gene: CST3: After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber. The GMS reviewes note that the primary phenotype is leukodystrophy and there is insufficient information to support a monogenic cause of neurodegenerative disorder.
Adult onset neurodegenerative disorder v8.14 CACNA1A_CAG Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from STR: CACNA1A_CAG.
Tag Q2_25_expert_review was removed from STR: CACNA1A_CAG.
Adult onset neurodegenerative disorder v8.14 CACNA1A_CAG Achchuthan Shanmugasundram reviewed STR: CACNA1A_CAG: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Adult onset neurodegenerative disorder v8.14 ATXN10_ATTCT Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from STR: ATXN10_ATTCT.
Adult onset neurodegenerative disorder v8.14 ATXN10_ATTCT Achchuthan Shanmugasundram reviewed STR: ATXN10_ATTCT: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Adult onset neurodegenerative disorder v8.14 CACNA1A_CAG Achchuthan Shanmugasundram Classified STR: CACNA1A_CAG as Green List (high evidence)
Adult onset neurodegenerative disorder v8.14 CACNA1A_CAG Achchuthan Shanmugasundram Str: cacna1a_cag has been classified as Green List (High Evidence).
Adult onset neurodegenerative disorder v8.13 ATXN10_ATTCT Achchuthan Shanmugasundram Classified STR: ATXN10_ATTCT as Green List (high evidence)
Adult onset neurodegenerative disorder v8.13 ATXN10_ATTCT Achchuthan Shanmugasundram Str: atxn10_attct has been classified as Green List (High Evidence).
Adult onset neurodegenerative disorder v8.12 SPTLC2 Achchuthan Shanmugasundram Source NHS GMS was added to SPTLC2.
Source Expert Review Green was added to SPTLC2.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset neurodegenerative disorder v8.12 SPTLC1 Achchuthan Shanmugasundram Source Expert Review Green was added to SPTLC1.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset neurodegenerative disorder v8.12 POLG Achchuthan Shanmugasundram Source Expert Review Green was added to POLG.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset leukodystrophy v6.10 NOTCH3 Achchuthan Shanmugasundram Tag Q3_25_MOI was removed from gene: NOTCH3.
Adult onset leukodystrophy v6.10 CST3 Achchuthan Shanmugasundram Tag Q2_25_ promote_green was removed from gene: CST3.
Tag Q2_25_ NHS_review was removed from gene: CST3.
Renal ciliopathies v4.11 DLG5 Eleanor Williams Tag Q2_25_ MOI was removed from gene: DLG5.
Tag Q2_25_ NHS_review was removed from gene: DLG5.
Renal ciliopathies v4.11 DLG5 Eleanor Williams commented on gene: DLG5: The mode of inheritance of this gene has been updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Adult onset leukodystrophy v6.10 NOTCH3 Achchuthan Shanmugasundram commented on gene: NOTCH3: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Adult onset leukodystrophy v6.10 CST3 Achchuthan Shanmugasundram commented on gene: CST3: The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.
Adult onset dystonia, chorea or related movement disorder v5.5 XK Achchuthan Shanmugasundram Tag Q1_25_ promote_green was removed from gene: XK.
Renal ciliopathies v4.10 DLG5 Eleanor Williams Source NHS GMS was added to DLG5.
Mode of inheritance for gene DLG5 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Adult onset leukodystrophy v6.9 NOTCH3 Achchuthan Shanmugasundram Mode of inheritance for gene NOTCH3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Adult onset leukodystrophy v6.9 CST3 Achchuthan Shanmugasundram Source Expert Review Green was added to CST3.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset dystonia, chorea or related movement disorder v5.5 SPR Achchuthan Shanmugasundram Tag Q1_25_ MOI was removed from gene: SPR.
Tag Q1_25_ demote_red was removed from gene: SPR.
Tag Q1_25_ expert_review was removed from gene: SPR.
Adult onset dystonia, chorea or related movement disorder v5.5 XK Achchuthan Shanmugasundram reviewed gene: XK: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset dystonia, chorea or related movement disorder v5.5 SPR Achchuthan Shanmugasundram reviewed gene: SPR: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Adult onset dystonia, chorea or related movement disorder v5.4 XK Achchuthan Shanmugasundram Source NHS GMS was added to XK.
Source Expert Review Green was added to XK.
Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Adult onset dystonia, chorea or related movement disorder v5.4 SPR Achchuthan Shanmugasundram Source Expert Review Red was added to SPR.
Mode of inheritance for gene SPR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Rating Changed from Green List (high evidence) to Red List (low evidence)
Paediatric or syndromic cardiomyopathy v7.96 RPL3L Arina Puzriakova Tag Q3_24_NHS_review was removed from gene: RPL3L.
Tag Q3_25_NHS_review tag was added to gene: RPL3L.
Early onset or syndromic epilepsy v8.133 GABRA3 Ida Ertmanska changed review comment from: Comment on list classification: There are numerous patients reported in literature with variants in GABRA3 and epilepsy. GOF variants cause a more severe, X-linked dominant phenotype (early-onset, treatment resistant epilepsy), while LOF variants usually result in a milder phenotype (epilepsy is rare) and an X-linked recessive inheritance pattern. Based on available evidence, GABRA3 should be promoted to Green with MOI X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males).; to: Comment on list classification: There are numerous patients reported in literature with variants in GABRA3 and epilepsy. GOF variants cause a more severe, X-linked dominant phenotype (early-onset, treatment resistant epilepsy), while LOF variants usually result in a milder phenotype (epilepsy is rare) and an X-linked recessive inheritance pattern. Functional evidence in mouse models supports these mechanistic findings. Based on available evidence, GABRA3 should be promoted to Green with MOI X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males).
Early onset or syndromic epilepsy v8.133 GABRA3 Ida Ertmanska changed review comment from: PMID: 41289009 Johannesen et al., 2025
Cohort of 43 individuals (18 males and 25 females) with GABRA3 variants - some reported previously. Detailed genotype–phenotype analyses showed that pathogenic GABRA3 variants can cause either dominant or recessive X-linked disorders. GOF variants caused severe phenotypes and followed X-linked dominant inheritance, while LOF variants resulted in milder phenotypes and followed an X-linked recessive pattern. 30 individuals are described in detail, others excluded due to family history or neutral impact of variant.

Among the 20 individuals with GOF variants, 85% (17/20) had epilepsy with a median age of onset at 33 months (range 2–252 months). In contrast, only 10% (1/10) with LOF variants had epilepsy, with onset at 4 months. Individuals with GOF variants were more likely to have severe ID (8/20 vs. 0/10 in LOF group). Female carriers of LOF variants were unaffected.

GABRA3 is linked to Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features, OMIM:301091 (OMIM accessed 10th Mar 2026).
Sources: Literature; to: PMID: 41289009 Johannesen et al., 2025
Cohort of 43 individuals (18 males and 25 females) with GABRA3 variants - some reported previously. Detailed genotype–phenotype analyses showed that pathogenic GABRA3 variants can cause either dominant or recessive X-linked disorders. GOF variants caused severe phenotypes and followed X-linked dominant inheritance, while LOF variants resulted in milder phenotypes and followed an X-linked recessive pattern. 30 individuals are described in detail, others excluded due to family history or neutral impact of variant.

Among the 20 individuals with GOF variants, 85% (17/20) had epilepsy with a median age of onset at 33 months (range 2–252 months). In contrast, only 10% (1/10) with LOF variants had epilepsy, with onset at 4 months. Individuals with GOF variants were more likely to have severe ID (8/20 vs. 0/10 in LOF group). Female carriers of LOF variants were unaffected.

Functional evidence from PMID: 41289009 - Gabra3 KO mice do not exhibit early mortality or seizures; in contrast, an engineered mouse model carrying the GOF p.(Gln242Leu) variant recapitulated key human findings: male pups were not viable, while female mice had increased mortality in the first 2 months of life, and developed seizures in adulthood.

GABRA3 is linked to Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features, OMIM:301091 (OMIM accessed 10th Mar 2026).
Sources: Literature
Intellectual disability v9.296 GABRA3 Ida Ertmanska Classified gene: GABRA3 as Amber List (moderate evidence)
Intellectual disability v9.296 GABRA3 Ida Ertmanska Added comment: Comment on list classification: There are numerous patients reported in literature with variants in GABRA3 and syndromic intellectual disability. GOF variants cause a more severe, X-linked dominant phenotype (severe ID, nonverbal), while LOF variants usually result in a milder phenotype (mild to moderate ID, language impairment) and an X-linked recessive inheritance pattern. Based on available evidence, GABRA3 should be promoted to Green with MOI X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males).
Intellectual disability v9.296 GABRA3 Ida Ertmanska Gene: gabra3 has been classified as Amber List (Moderate Evidence).
Early onset or syndromic epilepsy v8.133 GABRA3 Ida Ertmanska Classified gene: GABRA3 as Amber List (moderate evidence)
Early onset or syndromic epilepsy v8.133 GABRA3 Ida Ertmanska Added comment: Comment on list classification: There are numerous patients reported in literature with variants in GABRA3 and epilepsy. GOF variants cause a more severe, X-linked dominant phenotype (early-onset, treatment resistant epilepsy), while LOF variants usually result in a milder phenotype (epilepsy is rare) and an X-linked recessive inheritance pattern. Based on available evidence, GABRA3 should be promoted to Green with MOI X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males).
Early onset or syndromic epilepsy v8.133 GABRA3 Ida Ertmanska Gene: gabra3 has been classified as Amber List (Moderate Evidence).
Intellectual disability v9.295 GABRA3 Ida Ertmanska gene: GABRA3 was added
gene: GABRA3 was added to Intellectual disability. Sources: Literature
Q1_26_promote_green tags were added to gene: GABRA3.
Mode of inheritance for gene: GABRA3 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: GABRA3 were set to 41289009
Phenotypes for gene: GABRA3 were set to Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features, OMIM:301091
Review for gene: GABRA3 was set to GREEN
Added comment: PMID: 41289009 Johannesen et al., 2025
Cohort of 43 individuals (18 males and 25 females) with GABRA3 variants - some reported previously. Detailed genotype–phenotype analyses showed that pathogenic GABRA3 variants can cause either dominant or recessive X-linked disorders. GOF variants caused severe phenotypes and followed X-linked dominant inheritance, while LOF variants resulted in milder phenotypes and followed an X-linked recessive pattern. 30 individuals are described in detail, others excluded due to family history or neutral impact of variant.

Among the 20 individuals with GOF variants, 85% (17/20) had epilepsy with a median age of onset at 33 months (range 2–252 months). In contrast, only 10% (1/10) with LOF variants had epilepsy, with onset at 4 months. Individuals with GOF variants were more likely to have severe ID (8/20 vs. 0/10 in LOF group). Female carriers of LOF variants were unaffected.

GABRA3 is linked to Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features, OMIM:301091 (OMIM accessed 10th Mar 2026).
Sources: Literature
Early onset or syndromic epilepsy v8.132 GABRA3 Ida Ertmanska gene: GABRA3 was added
gene: GABRA3 was added to Early onset or syndromic epilepsy. Sources: Literature
Q1_26_promote_green tags were added to gene: GABRA3.
Mode of inheritance for gene: GABRA3 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: GABRA3 were set to 41289009
Phenotypes for gene: GABRA3 were set to Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features, OMIM:301091
Review for gene: GABRA3 was set to GREEN
Added comment: PMID: 41289009 Johannesen et al., 2025
Cohort of 43 individuals (18 males and 25 females) with GABRA3 variants - some reported previously. Detailed genotype–phenotype analyses showed that pathogenic GABRA3 variants can cause either dominant or recessive X-linked disorders. GOF variants caused severe phenotypes and followed X-linked dominant inheritance, while LOF variants resulted in milder phenotypes and followed an X-linked recessive pattern. 30 individuals are described in detail, others excluded due to family history or neutral impact of variant.

Among the 20 individuals with GOF variants, 85% (17/20) had epilepsy with a median age of onset at 33 months (range 2–252 months). In contrast, only 10% (1/10) with LOF variants had epilepsy, with onset at 4 months. Individuals with GOF variants were more likely to have severe ID (8/20 vs. 0/10 in LOF group). Female carriers of LOF variants were unaffected.

GABRA3 is linked to Epilepsy, X-linked 2, with or without impaired intellectual development and dysmorphic features, OMIM:301091 (OMIM accessed 10th Mar 2026).
Sources: Literature
Retinal disorders v8.95 TEAD1 Ida Ertmanska changed review comment from: PMID: 15016762 Fossdal et al., 2004
TEAD1 (c.1261T>C, p.Tyr421His) variant identified as causal for first reported Icelandic pedigree with SCRA. Variant not in gnomAD v4.1.0.

PMID: 26091538 Schrauwen et al., 2015
Patient with a de novo TEAD1 variant NM_021961.5:c.618G>A; p.Trp206Ter and Aicardi syndrome (infantile spasms, agenesis of the corpus callosum, and chorioretinal lacunae). Variant not reported in gnomAD v4.1.0.

PMID: 33864784 Grubisa et al., 2021
Serbian family with Sveinsson's chorioretinal atrophy (affected father and 2 children, diagnosed at 45, 20, and 15 years old). TEAD1 sequencing revealed c.1261T>A, p.Tyr421Asn in TEAD1 - not present in gnomAD v4.1.0. Family first reported in PMID: 15359244.

PMID: 40984966 Murati Calderon et al., 2025
Report of a 61-year-old Hispanic female patient with clinical features consistent with Sveinsson chorioretinal atrophy (SCRA), including bilateral peripapillary chorioretinal atrophy and early macular involvement. Heterozygous for TEAD1 variant (c.599C>T; p.Ala200Val) - 29 heterozygotes reported in gnomAD v4.1.0.

TEAD1 is linked to AD Sveinsson chorioretinal atrophy 108985 in OMIM (accessed 10th Mar 2026).; to: PMID: 15016762 Fossdal et al., 2004
TEAD1 (c.1261T>C, p.Tyr421His) variant identified as causal for first reported Icelandic pedigree with SCRA. Variant not in gnomAD v4.1.0.

PMID: 26091538 Schrauwen et al., 2015
Patient with a de novo TEAD1 variant NM_021961.5:c.618G>A; p.Trp206Ter and Aicardi syndrome (infantile spasms, agenesis of the corpus callosum, and chorioretinal lacunae). Variant not reported in gnomAD v4.1.0.

PMID: 33864784 Grubisa et al., 2021
Serbian family with Sveinsson's chorioretinal atrophy (affected father and 2 children, diagnosed at 45, 20, and 15 years old). TEAD1 sequencing revealed c.1261T>A, p.Tyr421Asn in TEAD1 - not present in gnomAD v4.1.0. Family first reported in PMID: 15359244.

PMID: 40984966 Murati Calderon et al., 2025
Report of a 61-year-old Hispanic female patient with clinical features consistent with Sveinsson chorioretinal atrophy (SCRA), including bilateral peripapillary chorioretinal atrophy and early macular involvement. Heterozygous for TEAD1 variant (c.599C>T; p.Ala200Val) - 29 heterozygotes reported in gnomAD v4.1.0. Used a retinal panel of 330 genes.

TEAD1 is linked to AD Sveinsson chorioretinal atrophy 108985 in OMIM (accessed 10th Mar 2026).
Retinal disorders v8.95 TEAD1 Ida Ertmanska Phenotypes for gene: TEAD1 were changed from to Sveinsson chorioretinal atrophy, OMIM:108985; helicoid peripapillary chorioretinal degeneration, MONDO:0007176
Retinal disorders v8.94 TEAD1 Ida Ertmanska Publications for gene: TEAD1 were set to
Retinal disorders v8.93 TEAD1 Ida Ertmanska Mode of inheritance for gene: TEAD1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Retinal disorders v8.92 TEAD1 Ida Ertmanska Classified gene: TEAD1 as Amber List (moderate evidence)
Retinal disorders v8.92 TEAD1 Ida Ertmanska Added comment: Comment on list classification: There are now more than 3 unrelated individuals of varied ancestry with heterozygous TEAD1 variants and retinal disease. There is good evidence of dominant segregation within pedigrees. Hence, TEAD1 should be promoted to Green at the next GMS update.
Retinal disorders v8.92 TEAD1 Ida Ertmanska Gene: tead1 has been classified as Amber List (Moderate Evidence).
Retinal disorders v8.91 TEAD1 Ida Ertmanska Tag Q1_26_promote_green tag was added to gene: TEAD1.
Retinal disorders v8.91 TEAD1 Ida Ertmanska reviewed gene: TEAD1: Rating: GREEN; Mode of pathogenicity: None; Publications: 15016762, 26091538, 33864784, 40984966; Phenotypes: Sveinsson chorioretinal atrophy, OMIM:108985, helicoid peripapillary chorioretinal degeneration, MONDO:0007176; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hereditary neuropathy or pain disorder v7.39 CHRNA3 Ida Ertmanska Tag Q1_26_promote_green tag was added to gene: CHRNA3.
Hereditary neuropathy or pain disorder v7.39 CHRNA3 Ida Ertmanska Classified gene: CHRNA3 as Amber List (moderate evidence)
Hereditary neuropathy or pain disorder v7.39 CHRNA3 Ida Ertmanska Added comment: Comment on list classification: There are more than 3 individuals reported in literature with an autonomic nervous system disorder and biallelic CHRNA3 variants. Individuals presented with severe orthostatic hypotension, nonreactive pupils, constipation, and bladder dysfunction. Hence, CHRNA3 should be promoted to Green at the next update.
Hereditary neuropathy or pain disorder v7.39 CHRNA3 Ida Ertmanska Gene: chrna3 has been classified as Amber List (Moderate Evidence).
Hereditary neuropathy or pain disorder v7.38 CHRNA3 Ida Ertmanska Phenotypes for gene: CHRNA3 were changed from Familial Autonomic Ganglionopathy to Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary CAKUT, OMIM:191800; autonomic nervous system disorder, MONDO:0001292
Hereditary neuropathy or pain disorder v7.37 CHRNA3 Ida Ertmanska Publications for gene: CHRNA3 were set to PMID: 33947782; 37161764
Hereditary neuropathy or pain disorder v7.36 CHRNA3 Ida Ertmanska edited their review of gene: CHRNA3: Changed rating: GREEN; Changed mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Hereditary neuropathy or pain disorder v7.36 CHRNA3 Ida Ertmanska reviewed gene: CHRNA3: Rating: ; Mode of pathogenicity: None; Publications: 38192228, 37161764, 33947782, 31708116; Phenotypes: Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary CAKUT, OMIM:191800; Mode of inheritance: None
Fetal anomalies v6.155 RNU7-1 Arina Puzriakova Publications for gene: RNU7-1 were set to
Fetal anomalies v6.154 RNU7-1 Arina Puzriakova Tag locus-type-rna-small-nuclear tag was added to gene: RNU7-1.
Fetal anomalies v6.154 RNU2-2P Arina Puzriakova commented on gene: RNU2-2P: The new-gene-name tag has been added as the latest HGNC symbol is RNU2-2.
Fetal anomalies v6.154 RNU2-2P Arina Puzriakova Tag new-gene-name tag was added to gene: RNU2-2P.
Tag locus-type-rna-small-nuclear tag was added to gene: RNU2-2P.
Fetal anomalies v6.154 RNU2-2P Arina Puzriakova Publications for gene: RNU2-2P were set to
Fetal anomalies v6.153 CLCNKB Arina Puzriakova commented on gene: CLCNKB: Digenic CLCNKA and CLCNKB variants are associated with Bartter syndrome, type 4b, digenic (OMIM:613090). The literature indicates that CLCNKB variants in patients are typically biallelic. While the Genomics England bioinformatics pipeline does not currently support the interpretation of digenic events, this panel is delivered by a specialised service with the capability to assess and report on these variants. Therefore, this gene has been included on the Fetal anomalies panel.
Fetal anomalies v6.153 CLCNKB Arina Puzriakova Publications for gene: CLCNKB were set to
Fetal anomalies v6.152 CLCNKB Arina Puzriakova Tag digenic tag was added to gene: CLCNKB.
Fetal anomalies v6.152 CLCNKA Arina Puzriakova changed review comment from: Digenic CLCNKA and CLCNKB variants are associated with Bartter syndrome, type 4b, digenic (OMIM:613090). While the Genomics England bioinformatics pipeline does not currently support the interpretation of digenic events, this panel is delivered by a specialised service with the capability to assess and report on these variants. Therefore, this gene has been included on the Fetal anomalies panel.; to: Digenic CLCNKA and CLCNKB variants are associated with Bartter syndrome, type 4b, digenic (OMIM:613090). The literature indicates that CLCNKA variants in patients are typically biallelic. While the Genomics England bioinformatics pipeline does not currently support the interpretation of digenic events, this panel is delivered by a specialised service with the capability to assess and report on these variants. Therefore, this gene has been included on the Fetal anomalies panel.
Fetal anomalies v6.152 CLCNKA Arina Puzriakova commented on gene: CLCNKA: Digenic CLCNKA and CLCNKB variants are associated with Bartter syndrome, type 4b, digenic (OMIM:613090). While the Genomics England bioinformatics pipeline does not currently support the interpretation of digenic events, this panel is delivered by a specialised service with the capability to assess and report on these variants. Therefore, this gene has been included on the Fetal anomalies panel.
Fetal anomalies v6.152 CLCNKA Arina Puzriakova Tag digenic tag was added to gene: CLCNKA.
Fetal anomalies v6.152 ACVR2B Arina Puzriakova Added phenotypes Heterotaxy, visceral, 4, autosomal for gene: ACVR2B
Fetal anomalies v6.152 SPTBN1 Arina Puzriakova Added phenotypes Developmental delay, impaired speech, and behavioral abnormalities, OMIM:619475 for gene: SPTBN1
Fetal anomalies v6.152 TAF13 Arina Puzriakova Added phenotypes Intellectual developmental disorder, autosomal recessive 60, OMIM:617432 for gene: TAF13
Fetal anomalies v6.152 PLXNB2 Arina Puzriakova Added phenotypes amelogenesis imperfecta, hearing loss and intellectual disability for gene: PLXNB2
Fetal anomalies v6.152 ZDHHC9 Arina Puzriakova Added phenotypes Intellectual developmental disorder, X-linked syndromic, Raymond type, OMIM:300799 for gene: ZDHHC9
Fetal anomalies v6.152 TRIO Arina Puzriakova Added phenotypes Intellectual developmental disorder, autosomal dominant 44, with microcephaly, OMIM:617061; Intellectual developmental disorder, autosomal dominant 63, with macrocephaly, OMIM:618825 for gene: TRIO
Fetal anomalies v6.152 SLC9A6 Arina Puzriakova Added phenotypes Intellectual developmental disorder, X-linked syndromic, Christianson type, OMIM:300243 for gene: SLC9A6
Fetal anomalies v6.152 SHROOM4 Arina Puzriakova Added phenotypes congenital anomalies of the urinary tract and the anorectal, cardiovascular and central nervous systems for gene: SHROOM4
Fetal anomalies v6.152 PLXNA1 Arina Puzriakova Added phenotypes Dworschak-Punetha neurodevelopmental syndrome, OMIM:619955 for gene: PLXNA1
Fetal anomalies v6.152 HDAC2 Arina Puzriakova Added phenotypes neurodevelopmental disorder for gene: HDAC2
Fetal anomalies v6.152 CHD8 Arina Puzriakova Added phenotypes Intellectual developmental disorder with autism and macrocephaly, OMIM:615032 for gene: CHD8
Fetal anomalies v6.152 BRWD3 Arina Puzriakova Added phenotypes Intellectual developmental disorder, X-linked 93, OMIM:300659 for gene: BRWD3
Fetal anomalies v6.152 SGCG Arina Puzriakova Added phenotypes Muscular dystrophy, limb-girdle, autosomal recessive 5, OMIM:253700 for gene: SGCG
Fetal anomalies v6.152 SGCD Arina Puzriakova Added phenotypes Muscular dystrophy, limb-girdle, autosomal recessive 6, OMIM:601287 for gene: SGCD
Fetal anomalies v6.152 SGCB Arina Puzriakova Added phenotypes Muscular dystrophy, limb-girdle, autosomal recessive 4, OMIM:604286 for gene: SGCB
Fetal anomalies v6.152 SGCA Arina Puzriakova Added phenotypes Muscular dystrophy, limb-girdle, autosomal recessive 3, OMIM:608099 for gene: SGCA
Fetal anomalies v6.152 PPP1R13L Arina Puzriakova Added phenotypes Arrhythmogenic cardiomyopathy with variable ectodermal abnormalities, OMIM:620519 for gene: PPP1R13L
Fetal anomalies v6.152 POLA1 Arina Puzriakova Added phenotypes Van Esch-O'Driscoll syndrome, OMIM:301030 for gene: POLA1
Fetal anomalies v6.152 PIGU Arina Puzriakova Added phenotypes Neurodevelopmental disorder with brain anomalies, seizures, and scoliosis, OMIM:618590 for gene: PIGU
Fetal anomalies v6.152 PIGK Arina Puzriakova Added phenotypes Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures, OMIM:618879 for gene: PIGK
Fetal anomalies v6.152 PIGB Arina Puzriakova Added phenotypes Developmental and epileptic encephalopathy 80, OMIM:618580 for gene: PIGB
Fetal anomalies v6.152 WDR11 Arina Puzriakova Added phenotypes Intellectual developmental disorder, autosomal recessive 78, OMIM:620237 for gene: WDR11
Fetal anomalies v6.152 WASHC3 Arina Puzriakova Added phenotypes short stature, distinctive facies, and neurodevelopmental abnormalities for gene: WASHC3
Fetal anomalies v6.152 VPS51 Arina Puzriakova Added phenotypes Pontocerebellar hypoplasia, type 13, OMIM:618606 for gene: VPS51
Fetal anomalies v6.152 VPS50 Arina Puzriakova Added phenotypes neurodevelopmental disorder with microcephaly, seizures and neonatal cholestasis, OMIM:619685 for gene: VPS50
Fetal anomalies v6.152 VPS33A Arina Puzriakova Added phenotypes Mucopolysaccharidosis-plus syndrome, OMIM:617303 for gene: VPS33A
Fetal anomalies v6.152 UGGT1 Arina Puzriakova Added phenotypes Congenital disorder of glycosylation for gene: UGGT1
Fetal anomalies v6.152 TUBGCP2 Arina Puzriakova Added phenotypes Pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures, OMIM:618737 for gene: TUBGCP2
Fetal anomalies v6.152 CLCNKB Arina Puzriakova Added phenotypes Bartter syndrome, type 4b, digenic, OMIM:613090; Bartter syndrome, type 3, OMIM:607364 for gene: CLCNKB
Fetal anomalies v6.152 CLCNKA Arina Puzriakova Added phenotypes Bartter syndrome, type 4b, digenic, OMIM:613090 for gene: CLCNKA
Fetal anomalies v6.152 DHX37 Arina Puzriakova Added phenotypes Neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies, OMIM:618731 for gene: DHX37
Fetal anomalies v6.152 SNAPIN Arina Puzriakova Added phenotypes neurodevelopmental disorder for gene: SNAPIN
Fetal anomalies v6.152 PATJ Arina Puzriakova Added phenotypes ciliopathy for gene: PATJ
Fetal anomalies v6.152 NSD2 Arina Puzriakova Added phenotypes Rauch-Steindl syndrome OMIM:619695 for gene: NSD2
Fetal anomalies v6.152 MNS1 Arina Puzriakova Added phenotypes Heterotaxy, visceral, 9, autosomal, with male infertility (Autosomal recessive) for gene: MNS1
Fetal anomalies v6.152 CCP110 Arina Puzriakova Added phenotypes ciliopathy for gene: CCP110
Fetal anomalies v6.152 PLXNB3 Arina Puzriakova Added phenotypes congenital heart disease with neurodevelopmental disabilities for gene: PLXNB3
Fetal anomalies v6.152 ARHGEF17 Arina Puzriakova Added phenotypes Neurodevelopmental disorder for gene: ARHGEF17
Fetal anomalies v6.152 FBXO11 Arina Puzriakova Added phenotypes Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities, OMIM:618089 for gene: FBXO11
Fetal anomalies v6.152 PPP1R12A Arina Puzriakova Added phenotypes Genitourinary and/or brain malformation syndrome, OMIM:618820 for gene: PPP1R12A
Fetal anomalies v6.152 PRDM13 Arina Puzriakova Added phenotypes Pontocerebellar hypoplasia, type 17, OMIM:619909 for gene: PRDM13
Fetal anomalies v6.152 CDC40 Arina Puzriakova Added phenotypes Pontocerebellar hypoplasia, type 15, OMIM:619302 for gene: CDC40
Fetal anomalies v6.152 PCLO Arina Puzriakova Added phenotypes Pontocerebellar hypoplasia, type 3, OMIM:608027 for gene: PCLO
Fetal anomalies v6.152 EXOSC1 Arina Puzriakova Added phenotypes Pontocerebellar hypoplasia, type 1F, OMIM:619304 for gene: EXOSC1
Fetal anomalies v6.152 EXOSC9 Arina Puzriakova Added phenotypes Pontocerebellar hypoplasia, type 1D, OMIM:618065 for gene: EXOSC9
Fetal anomalies v6.152 CCT8 Arina Puzriakova Added phenotypes Brain malformations, intellectual disability, and seizures for gene: CCT8
Fetal anomalies v6.152 CCM2L Arina Puzriakova Added phenotypes Tetralogy of Fallot for gene: CCM2L
Fetal anomalies v6.152 CCDC88A Arina Puzriakova Added phenotypes PEHO syndrome-like, OMIM:617507 for gene: CCDC88A
Fetal anomalies v6.152 CBFB Arina Puzriakova Added phenotypes Cleidocranial dysplasia-2, OMIM:620099 for gene: CBFB
Fetal anomalies v6.152 BRF2 Arina Puzriakova Added phenotypes Syndromic immunodeficiency and developmental disorders for gene: BRF2
Fetal anomalies v6.152 BRF1 Arina Puzriakova Added phenotypes Cerebellofaciodental syndrome, OMIM:616202 for gene: BRF1
Fetal anomalies v6.152 B9D1 Arina Puzriakova Added phenotypes Joubert syndrome 27, OMIM:617120 for gene: B9D1
Fetal anomalies v6.152 ARAF Arina Puzriakova Added phenotypes Lymphatic anomaly for gene: ARAF
Fetal anomalies v6.152 ANKRD17 Arina Puzriakova Added phenotypes Chopra-Amiel-Gordon syndrome, OMIM:619504 for gene: ANKRD17
Fetal anomalies v6.152 ALKBH8 Arina Puzriakova Added phenotypes Intellectual developmental disorder, autosomal recessive 71, OMIM:618504 for gene: ALKBH8
Fetal anomalies v6.152 AIMP2 Arina Puzriakova Added phenotypes Leukodystrophy, hypomyelinating, 17, OMIM:618006 for gene: AIMP2
Fetal anomalies v6.152 AIMP1 Arina Puzriakova Added phenotypes Leukodystrophy, hypomyelinating, 3, OMIM:260600 for gene: AIMP1
Fetal anomalies v6.152 ADAT3 Arina Puzriakova Added phenotypes Neurodevelopmental disorder with brain abnormalities, poor growth, and dysmorphic facies, OMIM:615286 for gene: ADAT3
Fetal anomalies v6.152 ADAMTS13 Arina Puzriakova Added phenotypes Hereditary thrombotic thrombocytopenic purpura, OMIM:274150 for gene: ADAMTS13
Fetal anomalies v6.152 ABI2 Arina Puzriakova Added phenotypes Intellectual disability, epilepsy, hypoplasia of the corpus callosum, and white matter abnormalities for gene: ABI2
Fetal anomalies v6.152 RHOBTB2 Arina Puzriakova Added phenotypes Developmental and epileptic encephalopathy 64, OMIM:618004 for gene: RHOBTB2
Fetal anomalies v6.152 RBBP5 Arina Puzriakova Added phenotypes neurodevelopmental disorder for gene: RBBP5
Fetal anomalies v6.152 RALGAPA1 Arina Puzriakova Added phenotypes Neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation, OMIM:618797 for gene: RALGAPA1
Fetal anomalies v6.152 RALA Arina Puzriakova Added phenotypes Hiatt-Neu-Cooper neurodevelopmental syndrome, OMIM:619311 for gene: RALA
Fetal anomalies v6.152 PPP1R21 Arina Puzriakova Added phenotypes Neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities, OMIM:619383 for gene: PPP1R21
Fetal anomalies v6.152 RNU2-2P Arina Puzriakova Added phenotypes neurodevelopmental disorder for gene: RNU2-2P
Fetal anomalies v6.152 ACVR1 Arina Puzriakova Added phenotypes Fibrodysplasia ossificans progressiva, OMIM:135100 for gene: ACVR1
Fetal anomalies v6.152 TMPRSS7 Arina Puzriakova Added phenotypes neurodevelopmental disorder for gene: TMPRSS7
Fetal anomalies v6.152 IL6ST Arina Puzriakova Added phenotypes Stuve-Wiedemann syndrome 2, OMIM:619751 for gene: IL6ST
Fetal anomalies v6.152 ZBTB7A Arina Puzriakova Added phenotypes Macrocephaly, neurodevelopmental delay, lymphoid hyperplasia, and persistent fetal hemoglobin, OMIM:619769 for gene: ZBTB7A
Fetal anomalies v6.152 ASXL2 Arina Puzriakova Added phenotypes Shashi-Pena syndrome, OMIM:617190 for gene: ASXL2
Fetal anomalies v6.152 ZPR1 Arina Puzriakova Added phenotypes Growth restriction, hypoplastic kidneys, alopecia, and distinctive facies, OMIM:619321 for gene: ZPR1
Fetal anomalies v6.152 ZNF668 Arina Puzriakova Added phenotypes Neurodevelopmental disorder with poor growth, large ears, and dysmorphic facies, OMIM:620194 for gene: ZNF668
Fetal anomalies v6.152 YY1AP1 Arina Puzriakova Added phenotypes Grange syndrome, OMIM:602531 for gene: YY1AP1
Fetal anomalies v6.152 WNK3 Arina Puzriakova Added phenotypes Prieto syndrome, OMIM:309610 for gene: WNK3
Fetal anomalies v6.152 TEK Arina Puzriakova Added phenotypes Venous malformations, multiple cutaneous and mucosal, OMIM:600195 for gene: TEK
Fetal anomalies v6.152 GATAD2B Arina Puzriakova Added phenotypes GAND syndrome, OMIM:615074 for gene: GATAD2B
Fetal anomalies v6.152 CACHD1 Arina Puzriakova Added phenotypes Neurodevelopmental syndrome with facial dysmorphism and multisystem congenital abnormalities for gene: CACHD1
Fetal anomalies v6.152 BAZ2B Arina Puzriakova Added phenotypes Complex neurodevelopmental disorder for gene: BAZ2B
Fetal anomalies v6.152 ARHGEF40 Arina Puzriakova Added phenotypes Congenital anomalies and developmental delay for gene: ARHGEF40
Fetal anomalies v6.152 SMARCC2 Arina Puzriakova Added phenotypes Coffin-Siris syndrome 8, OMIM:618362 for gene: SMARCC2
Fetal anomalies v6.152 SATB1 Arina Puzriakova Added phenotypes Developmental delay with dysmorphic facies and dental anomalies, OMIM:619228 for gene: SATB1
Fetal anomalies v6.152 SART3 Arina Puzriakova Added phenotypes Intellectual disability, Neurodevelopmental defects and Developmental delay with 46,XY Gonadal dysgenesis for gene: SART3
Fetal anomalies v6.152 ROBO4 Arina Puzriakova Added phenotypes Aortic valve disease 3, OMIM:618496 for gene: ROBO4
Fetal anomalies v6.152 RNF13 Arina Puzriakova Added phenotypes Developmental and epileptic encephalopathy 73, OMIM:618379 for gene: RNF13
Fetal anomalies v6.152 TMEM263 Arina Puzriakova Added phenotypes skeletal dysplasia for gene: TMEM263
Fetal anomalies v6.152 TMEM251 Arina Puzriakova Added phenotypes Dysostosis multiplex, Ain-Naz type, OMIM:619345 for gene: TMEM251
Fetal anomalies v6.152 SMG8 Arina Puzriakova Added phenotypes Alzahrani-Kuwahara syndrome, OMIM:619268 for gene: SMG8
Fetal anomalies v6.152 SMC5 Arina Puzriakova Added phenotypes Atelis syndrome 2, OMIM:620185 for gene: SMC5
Fetal anomalies v6.152 SLF2 Arina Puzriakova Added phenotypes Atelis syndrome 1, OMIM:620184 for gene: SLF2
Fetal anomalies v6.152 SLC5A6 Arina Puzriakova Added phenotypes Sodium-dependent multivitamin transporter deficiency, OMIM:618973 for gene: SLC5A6
Fetal anomalies v6.152 SLC13A1 Arina Puzriakova Added phenotypes short stature, scoliosis, and skeletal dysplasia for gene: SLC13A1
Fetal anomalies v6.152 SIX2 Arina Puzriakova Added phenotypes frontonasal dysplasia for gene: SIX2
Fetal anomalies v6.152 SIX1 Arina Puzriakova Added phenotypes Branchiootic syndrome 3, OMIM:608389 for gene: SIX1
Fetal anomalies v6.152 SELENON Arina Puzriakova Added phenotypes Congenital myopathy 3 with rigid spine; OMIM:602771 for gene: SELENON
Fetal anomalies v6.152 CSDE1 Arina Puzriakova Added phenotypes neurodevelopmental disorder for gene: CSDE1
Fetal anomalies v6.152 GINS3 Arina Puzriakova Added phenotypes Meier-Gorlin syndrome for gene: GINS3
Fetal anomalies v6.152 CAMSAP1 Arina Puzriakova Added phenotypes Cortical dysplasia, complex, with other brain malformations 12, OMIM:620316 for gene: CAMSAP1
Fetal anomalies v6.152 BUB1 Arina Puzriakova Added phenotypes Microcephaly 30, primary, autosomal recessive, OMIM:620183 for gene: BUB1
Fetal anomalies v6.152 RAB35 Arina Puzriakova Added phenotypes neurodevelopmental disorder for gene: RAB35
Fetal anomalies v6.152 ARF3 Arina Puzriakova Added phenotypes Neurodevelopmental disorder, brain abnormality for gene: ARF3
Fetal anomalies v6.152 ANKLE2 Arina Puzriakova Added phenotypes Microcephaly 16, primary, autosomal recessive, OMIM:616681 for gene: ANKLE2
Fetal anomalies v6.152 ETV2 Arina Puzriakova Added phenotypes congenital heart defects, vertebral abnormalities and preaxial polydactyly for gene: ETV2
Fetal anomalies v6.152 RAD51C Arina Puzriakova Added phenotypes Fanconi anemia, complementation group O, OMIM:613390 for gene: RAD51C
Fetal anomalies v6.152 CEP162 Arina Puzriakova Added phenotypes ciliopathy for gene: CEP162
Fetal anomalies v6.152 LINC01578 Arina Puzriakova Added phenotypes Neurodevelopmental disorder with dysmorphic facies, absent speech and ambulation, and brain abnormalities, OMIM:621012 for gene: LINC01578
Fetal anomalies v6.152 KCNN4 Arina Puzriakova Added phenotypes Dehydrated hereditary stomatocytosis 2, OMIM:616689 for gene: KCNN4
Fetal anomalies v6.152 MMP9 Arina Puzriakova Added phenotypes Metaphyseal anadysplasia 2, OMIM:613073 for gene: MMP9
Fetal anomalies v6.152 KDM4B Arina Puzriakova Added phenotypes Intellectual developmental disorder, autosomal dominant 65, OMIM:619320 for gene: KDM4B
Fetal anomalies v6.152 TMEM167A Arina Puzriakova Added phenotypes Microcephaly, epilepsy and diabetes syndrome for gene: TMEM167A
Fetal anomalies v6.152 PTBP1 Arina Puzriakova Added phenotypes neurodevelopmental disorder with skeletal dysplasia for gene: PTBP1
Fetal anomalies v6.152 PDIA6 Arina Puzriakova Added phenotypes Polycystic kidney disease, severe oligohydramnios, pulmonary hypoplasia, microcephaly, rib thoracic dysplasia, and global developmental delay for gene: PDIA6
Fetal anomalies v6.152 CRELD1 Arina Puzriakova Added phenotypes Jeffries-Lakhani neurodevelopmental syndrome, OMIM:620771 for gene: CRELD1
Fetal anomalies v6.152 DLG3 Arina Puzriakova Added phenotypes Intellectual developmental disorder, X-linked 90, OMIM:300850 for gene: DLG3
Fetal anomalies v6.152 SF1 Arina Puzriakova Added phenotypes neurodevelopmental disorder for gene: SF1
Fetal anomalies v6.152 TH Arina Puzriakova Added phenotypes Segawa syndrome, recessive, OMIM:605407 for gene: TH
Fetal anomalies v6.152 YRDC Arina Puzriakova Added phenotypes Galloway-Mowat syndrome 10, OMIM:619609 for gene: YRDC
Fetal anomalies v6.152 NUP133 Arina Puzriakova Added phenotypes Galloway-Mowat syndrome 8, OMIM:618349 for gene: NUP133
Fetal anomalies v6.152 GON7 Arina Puzriakova Added phenotypes Galloway-Mowat syndrome 9, OMIM:619603 for gene: GON7
Fetal anomalies v6.152 TPRKB Arina Puzriakova Added phenotypes Galloway-Mowat syndrome 5, OMIM:617731 for gene: TPRKB
Fetal anomalies v6.152 TP53RK Arina Puzriakova Added phenotypes Galloway-Mowat syndrome 4, OMIM:617730 for gene: TP53RK
Fetal anomalies v6.152 THUMPD1 Arina Puzriakova Added phenotypes Neurodevelopmental disorder with speech delay and variable ocular anomalies, OMIM:619989 for gene: THUMPD1
Fetal anomalies v6.152 TASP1 Arina Puzriakova Added phenotypes Suleiman-El-Hattab syndrome, OMIM:618950 for gene: TASP1
Fetal anomalies v6.152 SPOP Arina Puzriakova Added phenotypes Nabais Sa-de Vries syndrome, type 1, OMIM:618828; Nabais Sa-de Vries syndrome, type 2, OMIM:618829 for gene: SPOP
Fetal anomalies v6.152 SOX4 Arina Puzriakova Added phenotypes Intellectual developmental disorder with speech delay and dysmorphic facies, OMIM:618506 for gene: SOX4
Fetal anomalies v6.152 RSG1 Arina Puzriakova Added phenotypes ciliopathy for gene: RSG1
Fetal anomalies v6.152 DHRS3 Arina Puzriakova Added phenotypes coronal craniosynostosis, dysmorphic facial features, congenital heart disease, scoliosis for gene: DHRS3
Fetal anomalies v6.152 NR6A1 Arina Puzriakova Added phenotypes Oculovertebral syndrome, OMIM:621277 for gene: NR6A1
Fetal anomalies v6.152 WSB2 Arina Puzriakova Added phenotypes neurodevelopmental delay, dysmorphic features, brain structural abnormalities, growth restriction, hypotonia, microcephaly for gene: WSB2
Fetal anomalies v6.152 WDR91 Arina Puzriakova Added phenotypes microcephaly, dysmorphic features, organomegaly, psychomotor delay, hypotonia, sensorineural hearing impairment, visual impairment for gene: WDR91
Fetal anomalies v6.152 TTC26 Arina Puzriakova Added phenotypes Biliary, renal, neurologic, and skeletal syndrome, OMIM:619534 for gene: TTC26
Fetal anomalies v6.152 TMEM17 Arina Puzriakova Added phenotypes Ciliopathy for gene: TMEM17
Fetal anomalies v6.152 SMAD5 Arina Puzriakova Added phenotypes congenital heart disease for gene: SMAD5
Fetal anomalies v6.152 SCNM1 Arina Puzriakova Added phenotypes Orofaciodigital syndrome XIX; OMIM:620107 for gene: SCNM1
Fetal anomalies v6.152 RREB1 Arina Puzriakova Added phenotypes Rasopathy, mild dysmorphisms, congenital heart disease, genitourinary malformations, dental anomalies, and developmental delay for gene: RREB1
Fetal anomalies v6.152 PDCD6IP Arina Puzriakova Added phenotypes Microcephaly 29, primary, autosomal recessive, OMIM:620047 for gene: PDCD6IP
Fetal anomalies v6.152 GPKOW Arina Puzriakova Added phenotypes Intrauterine growth restriction, microcephaly/microencephaly, and eye, brain, skin, and skeletal abnormalities for gene: GPKOW
Fetal anomalies v6.152 CEP76 Arina Puzriakova Added phenotypes Joubert syndrome; Bardet-Biedl syndrome; retinitis pigmentosa; complex neurodevelopmental disorder MONDO:0100038 for gene: CEP76
Fetal anomalies v6.152 CCDC32 Arina Puzriakova Added phenotypes Cardiofacioneurodevelopmental syndrome, OMIM:619123 for gene: CCDC32
Fetal anomalies v6.152 BBIP1 Arina Puzriakova Added phenotypes Bardet-Biedl syndrome 18, MIM #615995 for gene: BBIP1
Fetal anomalies v6.152 RNU7-1 Arina Puzriakova Added phenotypes Aicardi-Goutieres syndrome 9 OMIM:619487 for gene: RNU7-1
Fetal anomalies v6.152 MYLPF Arina Puzriakova Added phenotypes Arthrogryposis, distal, type 1C, OMIM:617378 for gene: MYLPF
Fetal anomalies v6.152 LMOD2 Arina Puzriakova Added phenotypes Cardiomyopathy, dilated, 2G, OMIM:619897 for gene: LMOD2
Fetal anomalies v6.152 LHX2 Arina Puzriakova Added phenotypes neurodevelopmental disorder for gene: LHX2
Fetal anomalies v6.152 HMGB1 Arina Puzriakova Added phenotypes brachyphalangy, polydactyly and tibial aplasia syndrome for gene: HMGB1
Fetal anomalies v6.152 NUDCD2 Arina Puzriakova Added phenotypes multiple malformation syndrome with cholestasis and renal failure for gene: NUDCD2
Fetal anomalies v6.152 RNU5A-1 Arina Puzriakova Added phenotypes Neurodevelopmental disorder for gene: RNU5A-1
Fetal anomalies v6.152 RNPC3 Arina Puzriakova Added phenotypes Pituitary hormone deficiency, combined or isolated, 7, OMIM:618160 for gene: RNPC3
Fetal anomalies v6.152 RASA2 Arina Puzriakova Added phenotypes Noonan syndrome for gene: RASA2
Fetal anomalies v6.152 PURA Arina Puzriakova Added phenotypes Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties, OMIM:616158 for gene: PURA
Fetal anomalies v6.152 PLOD3 Arina Puzriakova Added phenotypes BCARD syndrome (lysyl hydroxylase 3 deficiency) OMIM:612394 for gene: PLOD3
Fetal anomalies v6.152 PDCD2 Arina Puzriakova Added phenotypes Nonimmune hydrops fetalis for gene: PDCD2
Fetal anomalies v6.152 NOVA2 Arina Puzriakova Added phenotypes neurodevelopmental disorder with hypotonia, neurological features, and brain abnormalities for gene: NOVA2
Fetal anomalies v6.152 NOTCH3 Arina Puzriakova Added phenotypes Lateral meningocele syndrome, OMIM:130720 for gene: NOTCH3
Fetal anomalies v6.152 BNIP1 Arina Puzriakova Added phenotypes Spondyloepiphyseal dysplasia, Holling type, OMIM:621345 for gene: BNIP1
Fetal anomalies v6.152 PACSIN3 Arina Puzriakova Added phenotypes Congenital myopathy 27, OMIM:621343 for gene: PACSIN3
Fetal anomalies v6.152 SEPHS1 Arina Puzriakova Added phenotypes Ververi-Brady syndrome 2, OMIM:621325 for gene: SEPHS1
Fetal anomalies v6.152 ELFN1 Arina Puzriakova Added phenotypes Dursun-Ozgul neurodevelopmental syndrome, OMIM:621344 for gene: ELFN1
Fetal anomalies v6.152 LSM1 Arina Puzriakova Added phenotypes FICUS syndrome, OMIM:621193 for gene: LSM1
Fetal anomalies v6.152 LEF1 Arina Puzriakova Added phenotypes Ectodermal dysplasia 17 with or without limb malformations, OMIM:621224 for gene: LEF1
Fetal anomalies v6.152 LDB3 Arina Puzriakova Added phenotypes Dilated cardiomyopathy for gene: LDB3
Fetal anomalies v6.152 IKZF2 Arina Puzriakova Added phenotypes Immunodysregulation, craniofacial anomalies, hearing impairment, athelia and developmental delay, OMIM:621234 for gene: IKZF2
Fetal anomalies v6.152 GTF3C3 Arina Puzriakova Added phenotypes Neurodevelopmental disorder with dysmorphic facies, brain anomalies, and seizures, OMIM:621201 for gene: GTF3C3
Fetal anomalies v6.152 GNPNAT1 Arina Puzriakova Added phenotypes Talipes equinovarus for gene: GNPNAT1
Fetal anomalies v6.152 FGF4 Arina Puzriakova Added phenotypes Short-rib thoracic dysplasia 22 without polydactyly, OMIM:621260 for gene: FGF4
Fetal anomalies v6.152 FEM1B Arina Puzriakova Added phenotypes Neurodevelopmental disorder with behavioral, ear, and skeletal abnormalities, OMIM:613539 for gene: FEM1B
Fetal anomalies v6.152 DOT1L Arina Puzriakova Added phenotypes Nil-Deshwar neurodevelopmental syndrome, OMIM:621265 for gene: DOT1L
Fetal anomalies v6.152 CDX1 Arina Puzriakova Added phenotypes Anorectal malformations for gene: CDX1
Fetal anomalies v6.152 CDH11 Arina Puzriakova Added phenotypes Teebi hypertelorism syndrome 2, OMIM:619736 for gene: CDH11
Fetal anomalies v6.152 FBXO28 Arina Puzriakova Added phenotypes Developmental and epileptic encephalopathy 100, OMIM:619777 for gene: FBXO28
Fetal anomalies v6.152 EMC10 Arina Puzriakova Added phenotypes Neurodevelopmental disorder with dysmorphic facies and variable seizures, OMIM:619264 for gene: EMC10
Fetal anomalies v6.152 EIF4A2 Arina Puzriakova Added phenotypes Neurodevelopmental disorder with hypotonia and speech delay, with or without seizures, OMIM:620455 for gene: EIF4A2
Fetal anomalies v6.152 EDN1 Arina Puzriakova Added phenotypes Auriculocondylar syndrome 3, OMIM:615706 for gene: EDN1
Fetal anomalies v6.152 DPH5 Arina Puzriakova Added phenotypes Neurodevelopmental disorder with short stature, prominent forehead, and feeding difficulties, OMIM:620070 for gene: DPH5
Fetal anomalies v6.152 DIP2C Arina Puzriakova Added phenotypes neurodevelopmental disorder, congenital heart defects for gene: DIP2C
Fetal anomalies v6.152 DHPS Arina Puzriakova Added phenotypes Neurodevelopmental disorder with seizures and speech and walking impairment, OMIM:618480 for gene: DHPS
Fetal anomalies v6.152 DDX23 Arina Puzriakova Added phenotypes Syndromic neurodevelopmental disorder for gene: DDX23
Fetal anomalies v6.152 CDC42BPB Arina Puzriakova Added phenotypes Chilton-Okur-Chung neurodevelopmental syndrome, OMIM:619841 for gene: CDC42BPB
Fetal anomalies v6.152 CDC42 Arina Puzriakova Added phenotypes Takenouchi-Kosaki syndrome, OMIM:616737 for gene: CDC42
Fetal anomalies v6.152 ADAMTS9 Arina Puzriakova Added phenotypes ciliopathy for gene: ADAMTS9
Fetal anomalies v6.152 YWHAE Arina Puzriakova Added phenotypes neurodevelopmental disorder for gene: YWHAE
Fetal anomalies v6.152 HNRNPH1 Arina Puzriakova Added phenotypes Neurodevelopmental disorder with craniofacial dysmorphism and skeletal defects, OMIM:620083 for gene: HNRNPH1
Fetal anomalies v6.152 HNRNPR Arina Puzriakova Added phenotypes Neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities, OMIM:620073 for gene: HNRNPR
Fetal anomalies v6.152 CLCN3 Arina Puzriakova Added phenotypes Neurodevelopmental disorder with hypotonia and brain abnormalities, OMIM:619512; Neurodevelopmental disorder with seizures and brain abnormalities, OMIM:619517 for gene: CLCN3
Fetal anomalies v6.152 ATP6V0A1 Arina Puzriakova Added phenotypes Developmental and epileptic encephalopathy 104, OMIM:619970; Neurodevelopmental disorder with epilepsy and brain atrophy, OMIM:619971 for gene: ATP6V0A1
Fetal anomalies v6.152 SKOR2 Arina Puzriakova Added phenotypes Cerebellar hypoplasia, neurodevelopmental delay for gene: SKOR2
Fetal anomalies v6.152 AMOT Arina Puzriakova Added phenotypes Congenital hydrocephalus for gene: AMOT
Fetal anomalies v6.152 PRKCI Arina Puzriakova Added phenotypes Van der Woude syndrome for gene: PRKCI
Fetal anomalies v6.152 TRPM4 Arina Puzriakova Added phenotypes Progressive familial heart block, type IB, OMIM:604559 for gene: TRPM4
Fetal anomalies v6.152 HERC2 Arina Puzriakova Added phenotypes Intellectual developmental disorder, autosomal recessive 38, OMIM:615516 for gene: HERC2
Fetal anomalies v6.152 HACD1 Arina Puzriakova Added phenotypes Congenital myopathy 11, OMIM:619967 for gene: HACD1
Fetal anomalies v6.152 H3F3B Arina Puzriakova Added phenotypes Bryant-Li-Bhoj neurodevelopmental syndrome 2, OMIM:619721 for gene: H3F3B
Fetal anomalies v6.152 FIBP Arina Puzriakova Added phenotypes Thauvin-Robinet-Faivre syndrome, OMIM:617107 for gene: FIBP
Fetal anomalies v6.152 FBXW7 Arina Puzriakova Added phenotypes Developmental delay, hypotonia, and impaired language, OMIM:620012 for gene: FBXW7
Fetal anomalies v6.152 PMS2 Arina Puzriakova Added phenotypes Mismatch repair cancer syndrome 4, OMIM:619101 for gene: PMS2
Fetal anomalies v6.152 MSH6 Arina Puzriakova Added phenotypes Mismatch repair cancer syndrome 3, OMIM:619097 for gene: MSH6
Fetal anomalies v6.152 MSH2 Arina Puzriakova Added phenotypes Mismatch repair cancer syndrome 2, OMIM:619096 for gene: MSH2
Fetal anomalies v6.152 MLH1 Arina Puzriakova Added phenotypes Mismatch repair cancer syndrome 1, OMIM:276300 for gene: MLH1
Fetal anomalies v6.152 KCNJ8 Arina Puzriakova Added phenotypes Cantu syndrome for gene: KCNJ8
Fetal anomalies v6.152 MAST1 Arina Puzriakova Added phenotypes Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations, OMIM:618273 for gene: MAST1
Fetal anomalies v6.152 MAPK8IP3 Arina Puzriakova Added phenotypes Neurodevelopmental disorder with or without variable brain abnormalities, OMIM:618443 for gene: MAPK8IP3
Fetal anomalies v6.152 LRRC32 Arina Puzriakova Added phenotypes Cleft palate, proliferative retinopathy, and developmental delay, OMIM:619047 for gene: LRRC32
Fetal anomalies v6.152 KIAA0556 Arina Puzriakova Added phenotypes Joubert syndrome 26, OMIM:616784 for gene: KIAA0556
Fetal anomalies v6.152 KCNQ5 Arina Puzriakova Added phenotypes Intellectual developmental disorder, autosomal dominant 46, OMIM:617601 for gene: KCNQ5
Fetal anomalies v6.152 INPP4A Arina Puzriakova Added phenotypes Neurodevelopmental disorder for gene: INPP4A
Fetal anomalies v6.152 IFT57 Arina Puzriakova Added phenotypes Bardet-Biedl Syndrome for gene: IFT57
Fetal anomalies v6.152 HEY2 Arina Puzriakova Added phenotypes Tetralogy of Fallot for gene: HEY2
Fetal anomalies v6.152 FOXI3 Arina Puzriakova Added phenotypes Craniofacial microsomia 2, OMIM:620444 for gene: FOXI3
Fetal anomalies v6.152 ENPP5 Arina Puzriakova Added phenotypes Skeletal dysplasia for gene: ENPP5
Fetal anomalies v6.152 EDA Arina Puzriakova Added phenotypes Hypohidrotic ectodermal dysplasia for gene: EDA
Fetal anomalies v6.152 DNAH14 Arina Puzriakova Added phenotypes Neurodevelopmental disorder for gene: DNAH14
Fetal anomalies v6.152 DDR1 Arina Puzriakova Added phenotypes Chondrodysplasia with multiple dislocations for gene: DDR1
Fetal anomalies v6.152 CPOX Arina Puzriakova Added phenotypes Harderoporphyria, OMIM:618892 for gene: CPOX
Rare genetic inflammatory skin disorders v4.18 PSMB10 Ida Ertmanska Tag Q1_26_promote_green tag was added to gene: PSMB10.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.80 PSMB10 Ida Ertmanska commented on gene: PSMB10: Comment on mode of inheritance: There are now more than 3 cases reported with both mono- and bi- allelic PSMB10 variants - presenting with a proteasome-associated autoinflammatory syndrome (with or without recurrent infections and chronic diarrhea). Hence, the MOI should be updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal.
Ectodermal dysplasia v4.25 PSMB10 Ida Ertmanska Classified gene: PSMB10 as Amber List (moderate evidence)
Ectodermal dysplasia v4.25 PSMB10 Ida Ertmanska Added comment: Comment on list classification: Monoallelic variants in PSMB10 have been reported to cause ectodermal dysplasia (alopecia, hypodontia, anonychia) in at least 5 unrelated individuals. Biallelic PSMB10 variants have not been linked to ectodermal dysplasia. Hence, the gene should be promoted to Green at the next update, with MOI MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted.
Ectodermal dysplasia v4.25 PSMB10 Ida Ertmanska Gene: psmb10 has been classified as Amber List (Moderate Evidence).
Ectodermal dysplasia v4.24 PSMB10 Ida Ertmanska gene: PSMB10 was added
gene: PSMB10 was added to Ectodermal dysplasia. Sources: Literature
Q1_26_promote_green tags were added to gene: PSMB10.
Mode of inheritance for gene: PSMB10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PSMB10 were set to 31783057; 36250618; 37600812; 38503300; 39734035
Phenotypes for gene: PSMB10 were set to Immunodeficiency 121 with autoinflammation, OMIM:620807; Proteasome-associated autoinflammatory syndrome 5, OMIM:619175
Review for gene: PSMB10 was set to GREEN
Added comment: MONOALLELIC CASES:
PMID: 36250618 Hebert et al., 2022
Patient 1 - severe combined immunodeficiency (SCID), ectodermal dysplasia, alopecia, hypodontia and anonychia; het de novo PSMB10 NM_002801.3: c.601G>A p.(Gly201Arg) variant.

PMID: 38503300 van der Made et al., 2024
Identified de novo PSMB10 mutations in 6 infants with SCID-Omenn syndrome. The syndromic presentation includes severe combined immunodeficiency (SCID), as well as diarrhea (6/6), alopecia (4/5), and desquamating erythematous rash (6/6). Reported variants: PSMB10: c.166G>C, p.Asp56His and c.601G>A/c.601G>C, p.Gly201Arg.

PMID: 39734035 Kuehn et al., 2025
Case report: white female with SCID, failure to thrive, diarrhea, and pruritic rash - symptom onset at 5-9 months. Trio WES identified a de novo PSMB10 variant in the proband: c.601G>A, p.Gly201Arg.

https://doi.org/10.70962/jhi.20250096 Fournier et al., 2025
Report of 3 patients with WES detected de novo heterozygous PSMB10 variants: c.614A>C p.Asp205Ala for PI and c.623C>T p.Ser208Phe for PII and PIII. Presentation: combined immunodeficiency (3/3), generalized erythroderma with desquamation (1/3), chronic diarrhea (2/3), severe liver disease (2/3).
Functional evidence: PSMB10 constructs were expressed in HEK293T cells prior to SDS-PAGE/western blotting analysis. The p.Asp205Ala and p.Ser208Phe PSMB10 variants were shown to impair proteasome assembly and exert dominant-negative effects on PSMB9 expression.

BIALLELIC CASES:
PMID: 31783057 Sarrabay et al., 2020
3yo girl with a proteasome-associated autoinflammatory syndrome, homozygous for a PSMB10 c.41T>C, p.Phe14Ser variant. She presented with failure to thrive, cutaneous rash, and hepatosplenomegaly. No immunodeficiency.

PMID: 37600812 Papendorf et al., 2023
Three unrelated Brazilian patients present with four novel PSMB10 variants. All share the p.Phe14del variant plus a different novel variant: p.Gly167Asp, p.Cys83Leufs*123, and c.710+1G>C. All 3 patients had skin lesions, recurrent fevers, failure to thrive; microcytic anemia ascertained in 2/3.

PSMB10 is now associated with AD Immunodeficiency 121 with autoinflammation, MIM:620807 & AR Proteasome-associated autoinflammatory syndrome 5, MIM:619175 (OMIM accessed 10th Mar 2026).
Sources: Literature
Rare genetic inflammatory skin disorders v4.18 PSMB10 Ida Ertmanska Classified gene: PSMB10 as Amber List (moderate evidence)
Rare genetic inflammatory skin disorders v4.18 PSMB10 Ida Ertmanska Added comment: Comment on list classification: There are now more than 3 cases reported with both mono- and bi- allelic PSMB10 variants, presenting with a chronic inflammatory skin rash. Hence, this gene should be promoted to Green with MOI BOTH monoallelic and biallelic, autosomal or pseudoautosomal.
Rare genetic inflammatory skin disorders v4.18 PSMB10 Ida Ertmanska Gene: psmb10 has been classified as Amber List (Moderate Evidence).
Rare genetic inflammatory skin disorders v4.17 PSMB10 Ida Ertmanska gene: PSMB10 was added
gene: PSMB10 was added to Rare genetic inflammatory skin disorders. Sources: Literature
Mode of inheritance for gene: PSMB10 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PSMB10 were set to 31783057; 36250618; 37600812; 38503300; 39734035
Phenotypes for gene: PSMB10 were set to Immunodeficiency 121 with autoinflammation, OMIM:620807; Proteasome-associated autoinflammatory syndrome 5, OMIM:619175
Review for gene: PSMB10 was set to GREEN
Added comment: MONOALLELIC CASES:
PMID: 36250618 Hebert et al., 2022
Patient 1 - severe combined immunodeficiency (SCID), ectodermal dysplasia, alopecia, hypodontia and anonychia; het de novo PSMB10 NM_002801.3: c.601G>A p.(Gly201Arg) variant.

PMID: 38503300 van der Made et al., 2024
Identified de novo PSMB10 mutations in 6 infants with SCID-Omenn syndrome. The syndromic presentation includes severe combined immunodeficiency (SCID), as well as diarrhea (6/6), alopecia (4/5), and desquamating erythematous rash (6/6). Reported variants: PSMB10: c.166G>C, p.Asp56His and c.601G>A/c.601G>C, p.Gly201Arg.

PMID: 39734035 Kuehn et al., 2025
Case report: white female with SCID, failure to thrive, diarrhea, and pruritic rash - symptom onset at 5-9 months. Trio WES identified a de novo PSMB10 variant in the proband: c.601G>A, p.Gly201Arg.

https://doi.org/10.70962/jhi.20250096 Fournier et al., 2025
Report of 3 patients with WES detected de novo heterozygous PSMB10 variants: c.614A>C p.Asp205Ala for PI and c.623C>T p.Ser208Phe for PII and PIII. Presentation: combined immunodeficiency (3/3), generalized erythroderma with desquamation (1/3), chronic diarrhea (2/3), severe liver disease (2/3).
Functional evidence: PSMB10 constructs were expressed in HEK293T cells prior to SDS-PAGE/western blotting analysis. The p.Asp205Ala and p.Ser208Phe PSMB10 variants were shown to impair proteasome assembly and exert dominant-negative effects on PSMB9 expression.

BIALLELIC CASES:
PMID: 31783057 Sarrabay et al., 2020
3yo girl with a proteasome-associated autoinflammatory syndrome, homozygous for a PSMB10 c.41T>C, p.Phe14Ser variant. She presented with failure to thrive, cutaneous rash, and hepatosplenomegaly. No immunodeficiency.

PMID: 37600812 Papendorf et al., 2023
Three unrelated Brazilian patients present with four novel PSMB10 variants. All share the p.Phe14del variant plus a different novel variant: p.Gly167Asp, p.Cys83Leufs*123, and c.710+1G>C. All 3 patients had skin lesions, recurrent fevers, failure to thrive; microcytic anemia ascertained in 2/3.

PSMB10 is now associated with AD Immunodeficiency 121 with autoinflammation, MIM:620807 & AR Proteasome-associated autoinflammatory syndrome 5, MIM:619175 (OMIM accessed 10th Mar 2026).
Sources: Literature
Primary immunodeficiency or monogenic inflammatory bowel disease v8.80 PSMB10 Ida Ertmanska Phenotypes for gene: PSMB10 were changed from Proteasome-associated autoinflammatory syndrome 5, OMIM:619175 to Immunodeficiency 121 with autoinflammation, OMIM:620807; Proteasome-associated autoinflammatory syndrome 5, OMIM:619175
Primary immunodeficiency or monogenic inflammatory bowel disease v8.79 PSMB10 Ida Ertmanska Publications for gene: PSMB10 were set to 31783057; 37600812
Primary immunodeficiency or monogenic inflammatory bowel disease v8.78 PSMB10 Ida Ertmanska Tag Q1_26_NHS_review tag was added to gene: PSMB10.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.78 PSMB10 Ida Ertmanska Tag Q1_26_MOI tag was added to gene: PSMB10.
Primary immunodeficiency or monogenic inflammatory bowel disease v8.78 PSMB10 Ida Ertmanska changed review comment from: MONOALLELIC CASES:
PMID: 36250618 Hebert et al., 2022
Patient 1 - severe combined immunodeficiency (SCID), ectodermal dysplasia, alopecia, hypodontia and anonychia; het de novo PSMB10 NM_002801.3: c.601G>A p.(Gly201Arg) variant.

PMID: 38503300 van der Made et al., 2024
Identified de novo PSMB10 mutations in 6 infants with SCID-Omenn syndrome. The syndromic presentation includes severe combined immunodeficiency (SCID), as well as diarrhea (6/6), alopecia (4/5), and desquamating erythematous rash (6/6). Reported variants: PSMB10: c.166G>C, p.Asp56His and c.601G>A/c.601G>C, p.Gly201Arg.

PMID: 39734035 Kuehn et al., 2025
Case report: white female with SCID, failure to thrive, diarrhea, and pruritic rash - symptom onset at 5-9 months. Trio WES identified a de novo PSMB10 variant in the proband: c.601G>A, p.Gly201Arg.

https://doi.org/10.70962/jhi.20250096 Fournier et al., 2025
Report of 3 patients with WES detected de novo heterozygous PSMB10 variants: c.614A>C p.Asp205Ala for PI and c.623C>T p.Ser208Phe for PII and PIII. Presentation: combined immunodeficiency (3/3), generalized erythroderma with desquamation (1/3), chronic diarrhea (2/3), severe liver disease (2/3).
Functional evidence: PSMB10 constructs were expressed in HEK293T cells prior to SDS-PAGE/western blotting analysis. The p.Asp205Ala and p.Ser208Phe PSMB10 variants were shown to impair proteasome assembly and exert dominant-negative effects on PSMB9 expression.

BIALLELIC CASES:
PMID: 31783057 Sarrabay et al., 2020
3yo girl with a proteasome-associated autoinflammatory syndrome, homozygous for a PSMB10 c.41T>C, p.Phe14Ser variant. She presented with failure to thrive, cutaneous rash, and hepatosplenomegaly. No immunodeficiency.

PMID: 37600812 Papendorf et al., 2023
Three unrelated Brazilian patients present with four novel PSMB10 variants. All share the p.Phe14del variant plus a different novel variant: p.Gly167Asp, p.Cys83Leufs*123, and c.710+1G>C.

PSMB10 is now associated with AD Immunodeficiency 121 with autoinflammation, MIM:620807 & AR Proteasome-associated autoinflammatory syndrome 5, MIM:619175 (OMIM accessed 10th Mar 2026).; to: MONOALLELIC CASES:
PMID: 36250618 Hebert et al., 2022
Patient 1 - severe combined immunodeficiency (SCID), ectodermal dysplasia, alopecia, hypodontia and anonychia; het de novo PSMB10 NM_002801.3: c.601G>A p.(Gly201Arg) variant.

PMID: 38503300 van der Made et al., 2024
Identified de novo PSMB10 mutations in 6 infants with SCID-Omenn syndrome. The syndromic presentation includes severe combined immunodeficiency (SCID), as well as diarrhea (6/6), alopecia (4/5), and desquamating erythematous rash (6/6). Reported variants: PSMB10: c.166G>C, p.Asp56His and c.601G>A/c.601G>C, p.Gly201Arg.

PMID: 39734035 Kuehn et al., 2025
Case report: white female with SCID, failure to thrive, diarrhea, and pruritic rash - symptom onset at 5-9 months. Trio WES identified a de novo PSMB10 variant in the proband: c.601G>A, p.Gly201Arg.

https://doi.org/10.70962/jhi.20250096 Fournier et al., 2025
Report of 3 patients with WES detected de novo heterozygous PSMB10 variants: c.614A>C p.Asp205Ala for PI and c.623C>T p.Ser208Phe for PII and PIII. Presentation: combined immunodeficiency (3/3), generalized erythroderma with desquamation (1/3), chronic diarrhea (2/3), severe liver disease (2/3).
Functional evidence: PSMB10 constructs were expressed in HEK293T cells prior to SDS-PAGE/western blotting analysis. The p.Asp205Ala and p.Ser208Phe PSMB10 variants were shown to impair proteasome assembly and exert dominant-negative effects on PSMB9 expression.

BIALLELIC CASES:
PMID: 31783057 Sarrabay et al., 2020
3yo girl with a proteasome-associated autoinflammatory syndrome, homozygous for a PSMB10 c.41T>C, p.Phe14Ser variant. She presented with failure to thrive, cutaneous rash, and hepatosplenomegaly. No immunodeficiency.

PMID: 37600812 Papendorf et al., 2023
Three unrelated Brazilian patients present with four novel PSMB10 variants. All share the p.Phe14del variant plus a different novel variant: p.Gly167Asp, p.Cys83Leufs*123, and c.710+1G>C. All 3 patients had skin lesions, recurrent fevers, failure to thrive; microcytic anemia ascertained in 2/3.

PSMB10 is now associated with AD Immunodeficiency 121 with autoinflammation, MIM:620807 & AR Proteasome-associated autoinflammatory syndrome 5, MIM:619175 (OMIM accessed 10th Mar 2026).
Primary immunodeficiency or monogenic inflammatory bowel disease v8.78 PSMB10 Ida Ertmanska edited their review of gene: PSMB10: Changed publications to: 31783057, 36250618, 37600812, 38503300, 39734035
Primary immunodeficiency or monogenic inflammatory bowel disease v8.78 PSMB10 Ida Ertmanska changed review comment from: PMID: 36250618 Hebert et al., 2022
Patient 1 - severe combined immunodeficiency (SCID), ectodermal dysplasia, alopecia, hypodontia and anonychia; het de novo PSMB10 NM_002801.3: c.601G>A p.(Gly201Arg) variant.

PMID: 38503300 van der Made et al., 2024
Identified de novo PSMB10 mutations in 6 infants with SCID-Omenn syndrome. The syndromic presentation includes severe combined immunodeficiency (SCID), as well as diarrhea (6/6), alopecia (4/5), and desquamating erythematous rash (6/6). Reported variants: PSMB10: c.166G>C, p.Asp56His and c.601G>A/c.601G>C, p.Gly201Arg.

PMID: 39734035 Kuehn et al., 2025
Case report: white female with SCID, failure to thrive, diarrhea, and pruritic rash - symptom onset at 5-9 months. Trio WES identified a de novo PSMB10 variant in the proband: c.601G>A, p.Gly201Arg.

https://doi.org/10.70962/jhi.20250096 Fournier et al., 2025
Report of 3 patients with WES detected de novo heterozygous PSMB10 variants: c.614A>C p.Asp205Ala for PI and c.623C>T p.Ser208Phe for PII and PIII. Presentation: combined immunodeficiency (3/3), generalized erythroderma with desquamation (1/3), chronic diarrhea (2/3), severe liver disease (2/3).
Functional evidence: PSMB10 constructs were expressed in HEK293T cells prior to SDS-PAGE/western blotting analysis. The p.Asp205Ala and p.Ser208Phe PSMB10 variants were shown to impair proteasome assembly and exert dominant-negative effects on PSMB9 expression.

PSMB10 is now associated with AD Immunodeficiency 121 with autoinflammation, MIM:620807 & AR Proteasome-associated autoinflammatory syndrome 5, MIM:619175 (OMIM accessed 10th Mar 2026).; to: MONOALLELIC CASES:
PMID: 36250618 Hebert et al., 2022
Patient 1 - severe combined immunodeficiency (SCID), ectodermal dysplasia, alopecia, hypodontia and anonychia; het de novo PSMB10 NM_002801.3: c.601G>A p.(Gly201Arg) variant.

PMID: 38503300 van der Made et al., 2024
Identified de novo PSMB10 mutations in 6 infants with SCID-Omenn syndrome. The syndromic presentation includes severe combined immunodeficiency (SCID), as well as diarrhea (6/6), alopecia (4/5), and desquamating erythematous rash (6/6). Reported variants: PSMB10: c.166G>C, p.Asp56His and c.601G>A/c.601G>C, p.Gly201Arg.

PMID: 39734035 Kuehn et al., 2025
Case report: white female with SCID, failure to thrive, diarrhea, and pruritic rash - symptom onset at 5-9 months. Trio WES identified a de novo PSMB10 variant in the proband: c.601G>A, p.Gly201Arg.

https://doi.org/10.70962/jhi.20250096 Fournier et al., 2025
Report of 3 patients with WES detected de novo heterozygous PSMB10 variants: c.614A>C p.Asp205Ala for PI and c.623C>T p.Ser208Phe for PII and PIII. Presentation: combined immunodeficiency (3/3), generalized erythroderma with desquamation (1/3), chronic diarrhea (2/3), severe liver disease (2/3).
Functional evidence: PSMB10 constructs were expressed in HEK293T cells prior to SDS-PAGE/western blotting analysis. The p.Asp205Ala and p.Ser208Phe PSMB10 variants were shown to impair proteasome assembly and exert dominant-negative effects on PSMB9 expression.

BIALLELIC CASES:
PMID: 31783057 Sarrabay et al., 2020
3yo girl with a proteasome-associated autoinflammatory syndrome, homozygous for a PSMB10 c.41T>C, p.Phe14Ser variant. She presented with failure to thrive, cutaneous rash, and hepatosplenomegaly. No immunodeficiency.

PMID: 37600812 Papendorf et al., 2023
Three unrelated Brazilian patients present with four novel PSMB10 variants. All share the p.Phe14del variant plus a different novel variant: p.Gly167Asp, p.Cys83Leufs*123, and c.710+1G>C.

PSMB10 is now associated with AD Immunodeficiency 121 with autoinflammation, MIM:620807 & AR Proteasome-associated autoinflammatory syndrome 5, MIM:619175 (OMIM accessed 10th Mar 2026).
Primary immunodeficiency or monogenic inflammatory bowel disease v8.78 PSMB10 Ida Ertmanska reviewed gene: PSMB10: Rating: GREEN; Mode of pathogenicity: None; Publications: 36250618, 38503300, 39734035; Phenotypes: Immunodeficiency 121 with autoinflammation, OMIM:620807, Proteasome-associated autoinflammatory syndrome 5, OMIM:619175; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v6.151 ZNF865 Ida Ertmanska gene: ZNF865 was added
gene: ZNF865 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ZNF865 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNF865 were set to 40936200
Phenotypes for gene: ZNF865 were set to neurodevelopmental disorder, MONDO:0700092
Review for gene: ZNF865 was set to GREEN
Added comment: PMID: 40936200 Bradbrook et al., 2025 Report of 18 unrelated individuals (Caucasian / Latino ethnicity) with developmental delay and shared dysmorphic features, harbouring heterozygous variants in ZNF865. Method: WGS / WES. Majority described as severely delayed, with speech delay and moderate to severe learning difficulties; avg age of walking = 24 months, 9/18 patients presented with hypotonia, 1 patient diagnosed with epilepsy, 9/15 had digit anomalies. On MRI, 8/14 patients had brain abnormalities, including hypoplasia of corpus callosum and ventriculomegaly - may be detected prenatally?. Shared dysmorphic features: broad nasal bridge, hypertelorism, low-set ears. 14 unique variants (nonsense of frameshift) were detected, mostly towards the C-terminus. Variants were confirmed as de novo in 15 individuals.
This gene is not yet linked to any phenotype in OMIM (accessed 30th Dec 2025).
Sources: Literature
Malformations of cortical development v7.34 ZNF865 Ida Ertmanska Classified gene: ZNF865 as Amber List (moderate evidence)
Malformations of cortical development v7.34 ZNF865 Ida Ertmanska Added comment: Comment on list classification: There are 8 individuals reported in literature with heterozygous ZNF865 variants and brain abnormalities, including hypoplasia of corpus callosum and ventriculomegaly. Based on available evidence, this gene should be promoted to Green at the next GMS update.
Malformations of cortical development v7.34 ZNF865 Ida Ertmanska Gene: znf865 has been classified as Amber List (Moderate Evidence).
Intellectual disability v9.294 ZNF865 Ida Ertmanska Mode of inheritance for gene: ZNF865 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Malformations of cortical development v7.33 ZNF865 Ida Ertmanska gene: ZNF865 was added
gene: ZNF865 was added to Malformations of cortical development. Sources: Literature
Q1_26_promote_green tags were added to gene: ZNF865.
Mode of inheritance for gene: ZNF865 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZNF865 were set to 40936200
Phenotypes for gene: ZNF865 were set to neurodevelopmental disorder, MONDO:0700092
Review for gene: ZNF865 was set to GREEN
Added comment: PMID: 40936200 Bradbrook et al., 2025
Report of 18 unrelated individuals (Caucasian / Latino ethnicity) with developmental delay and shared dysmorphic features, harbouring heterozygous variants in ZNF865. Method: WGS / WES. Majority described as severely delayed, with speech delay and moderate to severe learning difficulties; avg age of walking = 24 months, 9/18 patients presented with hypotonia, 1 patient diagnosed with epilepsy, 9/15 had digit anomalies.
On MRI, 8/14 patients had brain abnormalities, including hypoplasia of corpus callosum and ventriculomegaly. Shared dysmorphic features: broad nasal bridge, hypertelorism, low-set ears.
14 unique variants (nonsense of frameshift) were detected, mostly towards the C-terminus. Variants were confirmed as de novo in 15 individuals.

This gene is not yet linked to any phenotype in OMIM (accessed 10th Mar 2026).
Sources: Literature
Intellectual disability v9.293 ZNF865 Ida Ertmanska edited their review of gene: ZNF865: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ataxia and cerebellar anomalies - narrow panel v8.64 ZNF865 Ida Ertmanska edited their review of gene: ZNF865: Changed rating: RED
Ataxia and cerebellar anomalies - narrow panel v8.64 ZNF865 Ida Ertmanska Deleted their comment
Ataxia and cerebellar anomalies - narrow panel v8.64 ZNF865 Ida Ertmanska commented on gene: ZNF865: This gene is more appropriate for the Malformations of cortical development panel. Added curated_removed tag.
Ataxia and cerebellar anomalies - narrow panel v8.64 ZNF865 Ida Ertmanska Classified gene: ZNF865 as No list
Ataxia and cerebellar anomalies - narrow panel v8.64 ZNF865 Ida Ertmanska Gene: znf865 has been removed from the panel.
Ataxia and cerebellar anomalies - narrow panel v8.63 ZNF865 Ida Ertmanska Tag curated_removed tag was added to gene: ZNF865.
Ataxia and cerebellar anomalies - narrow panel v8.63 ZNF865 Ida Ertmanska Tag Q4_25_promote_green was removed from gene: ZNF865.
Fetal anomalies v6.150 SGCG Arina Puzriakova edited their review of gene: SGCG: Changed rating: RED
Fetal anomalies v6.150 ACVR2B Arina Puzriakova edited their review of gene: ACVR2B: Changed rating: RED
Fetal anomalies v6.150 ZPR1 Arina Puzriakova edited their review of gene: ZPR1: Changed rating: GREEN
Fetal anomalies v6.150 ZNF668 Arina Puzriakova edited their review of gene: ZNF668: Changed rating: GREEN
Fetal anomalies v6.150 ZBTB7A Arina Puzriakova edited their review of gene: ZBTB7A: Changed rating: GREEN
Fetal anomalies v6.150 YY1AP1 Arina Puzriakova edited their review of gene: YY1AP1: Changed rating: GREEN
Fetal anomalies v6.150 WNK3 Arina Puzriakova edited their review of gene: WNK3: Changed rating: GREEN
Fetal anomalies v6.150 VPS51 Arina Puzriakova edited their review of gene: VPS51: Changed rating: GREEN
Fetal anomalies v6.150 VPS50 Arina Puzriakova edited their review of gene: VPS50: Changed rating: GREEN
Fetal anomalies v6.150 VPS33A Arina Puzriakova edited their review of gene: VPS33A: Changed rating: GREEN
Fetal anomalies v6.150 UGGT1 Arina Puzriakova edited their review of gene: UGGT1: Changed rating: GREEN
Fetal anomalies v6.150 TTC26 Arina Puzriakova edited their review of gene: TTC26: Changed rating: GREEN
Fetal anomalies v6.150 TPRKB Arina Puzriakova edited their review of gene: TPRKB: Changed rating: GREEN
Fetal anomalies v6.150 TP53RK Arina Puzriakova edited their review of gene: TP53RK: Changed rating: GREEN
Fetal anomalies v6.150 TMEM251 Arina Puzriakova edited their review of gene: TMEM251: Changed rating: GREEN
Fetal anomalies v6.150 TMEM17 Arina Puzriakova edited their review of gene: TMEM17: Changed rating: GREEN
Fetal anomalies v6.150 TMEM167A Arina Puzriakova edited their review of gene: TMEM167A: Changed rating: GREEN
Fetal anomalies v6.150 THUMPD1 Arina Puzriakova edited their review of gene: THUMPD1: Changed rating: GREEN
Fetal anomalies v6.150 TASP1 Arina Puzriakova edited their review of gene: TASP1: Changed rating: GREEN
Fetal anomalies v6.150 SOX4 Arina Puzriakova edited their review of gene: SOX4: Changed rating: GREEN
Fetal anomalies v6.150 SMG8 Arina Puzriakova edited their review of gene: SMG8: Changed rating: GREEN
Fetal anomalies v6.150 SMC5 Arina Puzriakova edited their review of gene: SMC5: Changed rating: GREEN
Fetal anomalies v6.150 SMARCC2 Arina Puzriakova edited their review of gene: SMARCC2: Changed rating: GREEN
Fetal anomalies v6.150 SLF2 Arina Puzriakova edited their review of gene: SLF2: Changed rating: GREEN
Fetal anomalies v6.150 SLC5A6 Arina Puzriakova edited their review of gene: SLC5A6: Changed rating: GREEN
Fetal anomalies v6.150 SKOR2 Arina Puzriakova edited their review of gene: SKOR2: Changed rating: GREEN
Fetal anomalies v6.150 SIX2 Arina Puzriakova edited their review of gene: SIX2: Changed rating: GREEN
Fetal anomalies v6.150 SCNM1 Arina Puzriakova edited their review of gene: SCNM1: Changed rating: GREEN
Fetal anomalies v6.150 SATB1 Arina Puzriakova edited their review of gene: SATB1: Changed rating: GREEN
Fetal anomalies v6.150 SART3 Arina Puzriakova edited their review of gene: SART3: Changed rating: GREEN
Fetal anomalies v6.150 RSG1 Arina Puzriakova edited their review of gene: RSG1: Changed rating: GREEN
Fetal anomalies v6.150 RNU7-1 Arina Puzriakova edited their review of gene: RNU7-1: Changed rating: GREEN
Fetal anomalies v6.150 RHOBTB2 Arina Puzriakova edited their review of gene: RHOBTB2: Changed rating: GREEN
Fetal anomalies v6.150 RBBP5 Arina Puzriakova edited their review of gene: RBBP5: Changed rating: GREEN
Fetal anomalies v6.150 RALGAPA1 Arina Puzriakova edited their review of gene: RALGAPA1: Changed rating: GREEN
Fetal anomalies v6.150 RALA Arina Puzriakova edited their review of gene: RALA: Changed rating: GREEN
Fetal anomalies v6.150 PRKCI Arina Puzriakova edited their review of gene: PRKCI: Changed rating: GREEN
Fetal anomalies v6.150 PPP1R21 Arina Puzriakova edited their review of gene: PPP1R21: Changed rating: GREEN
Fetal anomalies v6.150 PLXNA1 Arina Puzriakova edited their review of gene: PLXNA1: Changed rating: GREEN
Fetal anomalies v6.150 PIGU Arina Puzriakova edited their review of gene: PIGU: Changed rating: GREEN
Fetal anomalies v6.150 PIGK Arina Puzriakova edited their review of gene: PIGK: Changed rating: GREEN
Fetal anomalies v6.150 PIGB Arina Puzriakova edited their review of gene: PIGB: Changed rating: GREEN
Fetal anomalies v6.150 PDIA6 Arina Puzriakova edited their review of gene: PDIA6: Changed rating: GREEN
Fetal anomalies v6.150 NUP133 Arina Puzriakova edited their review of gene: NUP133: Changed rating: GREEN
Fetal anomalies v6.150 NR6A1 Arina Puzriakova edited their review of gene: NR6A1: Changed rating: GREEN
Fetal anomalies v6.150 MYLPF Arina Puzriakova edited their review of gene: MYLPF: Changed rating: GREEN
Fetal anomalies v6.150 LSM1 Arina Puzriakova edited their review of gene: LSM1: Changed rating: GREEN
Fetal anomalies v6.150 LRRC32 Arina Puzriakova edited their review of gene: LRRC32: Changed rating: GREEN
Fetal anomalies v6.150 LMOD2 Arina Puzriakova edited their review of gene: LMOD2: Changed rating: GREEN
Fetal anomalies v6.150 LEF1 Arina Puzriakova edited their review of gene: LEF1: Changed rating: GREEN
Fetal anomalies v6.150 KDM4B Arina Puzriakova edited their review of gene: KDM4B: Changed rating: GREEN
Fetal anomalies v6.150 INPP4A Arina Puzriakova edited their review of gene: INPP4A: Changed rating: GREEN
Fetal anomalies v6.150 IL6ST Arina Puzriakova edited their review of gene: IL6ST: Changed rating: GREEN
Fetal anomalies v6.150 IFT57 Arina Puzriakova edited their review of gene: IFT57: Changed rating: GREEN
Fetal anomalies v6.150 HNRNPR Arina Puzriakova edited their review of gene: HNRNPR: Changed rating: GREEN
Fetal anomalies v6.150 HNRNPH1 Arina Puzriakova edited their review of gene: HNRNPH1: Changed rating: GREEN
Fetal anomalies v6.150 HERC2 Arina Puzriakova edited their review of gene: HERC2: Changed rating: GREEN
Fetal anomalies v6.150 H3F3B Arina Puzriakova edited their review of gene: H3F3B: Changed rating: GREEN
Fetal anomalies v6.150 GTF3C3 Arina Puzriakova edited their review of gene: GTF3C3: Changed rating: GREEN
Fetal anomalies v6.150 GON7 Arina Puzriakova edited their review of gene: GON7: Changed rating: GREEN
Fetal anomalies v6.150 GINS3 Arina Puzriakova edited their review of gene: GINS3: Changed rating: GREEN
Fetal anomalies v6.150 FGF4 Arina Puzriakova edited their review of gene: FGF4: Changed rating: GREEN
Fetal anomalies v6.150 FEM1B Arina Puzriakova edited their review of gene: FEM1B: Changed rating: GREEN
Fetal anomalies v6.150 FBXW7 Arina Puzriakova edited their review of gene: FBXW7: Changed rating: GREEN
Fetal anomalies v6.150 FBXO28 Arina Puzriakova edited their review of gene: FBXO28: Changed rating: GREEN
Fetal anomalies v6.150 EMC10 Arina Puzriakova edited their review of gene: EMC10: Changed rating: GREEN
Fetal anomalies v6.150 EIF4A2 Arina Puzriakova edited their review of gene: EIF4A2: Changed rating: GREEN
Fetal anomalies v6.150 DPH5 Arina Puzriakova edited their review of gene: DPH5: Changed rating: GREEN
Fetal anomalies v6.150 DOT1L Arina Puzriakova edited their review of gene: DOT1L: Changed rating: GREEN
Fetal anomalies v6.150 CSDE1 Arina Puzriakova edited their review of gene: CSDE1: Changed rating: GREEN
Fetal anomalies v6.150 CLCNKA Arina Puzriakova edited their review of gene: CLCNKA: Changed rating: GREEN
Fetal anomalies v6.150 CLCN3 Arina Puzriakova edited their review of gene: CLCN3: Changed rating: GREEN
Fetal anomalies v6.150 CEP76 Arina Puzriakova edited their review of gene: CEP76: Changed rating: GREEN
Fetal anomalies v6.150 CDC42BPB Arina Puzriakova edited their review of gene: CDC42BPB: Changed rating: GREEN
Fetal anomalies v6.150 CDC42 Arina Puzriakova edited their review of gene: CDC42: Changed rating: GREEN
Fetal anomalies v6.150 CCDC88A Arina Puzriakova edited their review of gene: CCDC88A: Changed rating: GREEN
Fetal anomalies v6.150 CCDC32 Arina Puzriakova edited their review of gene: CCDC32: Changed rating: GREEN
Fetal anomalies v6.150 CBFB Arina Puzriakova edited their review of gene: CBFB: Changed rating: GREEN
Fetal anomalies v6.150 CAMSAP1 Arina Puzriakova edited their review of gene: CAMSAP1: Changed rating: GREEN
Fetal anomalies v6.150 BRF2 Arina Puzriakova edited their review of gene: BRF2: Changed rating: GREEN
Fetal anomalies v6.150 BBIP1 Arina Puzriakova edited their review of gene: BBIP1: Changed rating: GREEN
Fetal anomalies v6.150 ARF3 Arina Puzriakova edited their review of gene: ARF3: Changed rating: GREEN
Fetal anomalies v6.150 ADAT3 Arina Puzriakova edited their review of gene: ADAT3: Changed rating: GREEN
Fetal anomalies v6.150 ABI2 Arina Puzriakova edited their review of gene: ABI2: Changed rating: GREEN
Fetal anomalies v6.150 YRDC Arina Puzriakova edited their review of gene: YRDC: Changed rating: GREEN
Fetal anomalies v6.150 WSB2 Arina Puzriakova edited their review of gene: WSB2: Changed rating: GREEN
Fetal anomalies v6.150 WDR91 Arina Puzriakova edited their review of gene: WDR91: Changed rating: GREEN
Fetal anomalies v6.150 TUBGCP2 Arina Puzriakova edited their review of gene: TUBGCP2: Changed rating: GREEN
Fetal anomalies v6.150 TRIO Arina Puzriakova edited their review of gene: TRIO: Changed rating: GREEN
Fetal anomalies v6.150 SHROOM4 Arina Puzriakova edited their review of gene: SHROOM4: Changed rating: GREEN
Fetal anomalies v6.150 SELENON Arina Puzriakova edited their review of gene: SELENON: Changed rating: GREEN
Fetal anomalies v6.150 PDCD2 Arina Puzriakova edited their review of gene: PDCD2: Changed rating: GREEN
Fetal anomalies v6.150 NOVA2 Arina Puzriakova edited their review of gene: NOVA2: Changed rating: GREEN
Fetal anomalies v6.150 MAST1 Arina Puzriakova edited their review of gene: MAST1: Changed rating: GREEN
Fetal anomalies v6.150 MAPK8IP3 Arina Puzriakova edited their review of gene: MAPK8IP3: Changed rating: GREEN
Fetal anomalies v6.150 KIAA0556 Arina Puzriakova edited their review of gene: KIAA0556: Changed rating: GREEN
Fetal anomalies v6.150 KCNJ8 Arina Puzriakova edited their review of gene: KCNJ8: Changed rating: GREEN
Fetal anomalies v6.150 HMGB1 Arina Puzriakova edited their review of gene: HMGB1: Changed rating: GREEN
Fetal anomalies v6.150 GPKOW Arina Puzriakova edited their review of gene: GPKOW: Changed rating: GREEN
Fetal anomalies v6.150 GATAD2B Arina Puzriakova edited their review of gene: GATAD2B: Changed rating: GREEN
Fetal anomalies v6.150 FOXI3 Arina Puzriakova edited their review of gene: FOXI3: Changed rating: GREEN
Fetal anomalies v6.150 CLCNKB Arina Puzriakova edited their review of gene: CLCNKB: Changed rating: GREEN
Fetal anomalies v6.150 CACHD1 Arina Puzriakova edited their review of gene: CACHD1: Changed rating: GREEN
Fetal anomalies v6.150 BRF1 Arina Puzriakova edited their review of gene: BRF1: Changed rating: GREEN
Fetal anomalies v6.150 B9D1 Arina Puzriakova edited their review of gene: B9D1: Changed rating: GREEN
Fetal anomalies v6.150 ASXL2 Arina Puzriakova edited their review of gene: ASXL2: Changed rating: GREEN
Fetal anomalies v6.150 ANKLE2 Arina Puzriakova edited their review of gene: ANKLE2: Changed rating: GREEN
Fetal anomalies v6.150 ACVR1 Arina Puzriakova edited their review of gene: ACVR1: Changed rating: GREEN
Fetal anomalies v6.149 SGCG Arina Puzriakova commented on gene: SGCG: The rating of this gene has been updated to Red following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 ACVR2B Arina Puzriakova commented on gene: ACVR2B: The rating of this gene has been updated to Red following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 ZPR1 Arina Puzriakova commented on gene: ZPR1: 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.
Fetal anomalies v6.149 ZNF668 Arina Puzriakova commented on gene: ZNF668: 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.
Fetal anomalies v6.149 ZBTB7A Arina Puzriakova commented on gene: ZBTB7A: 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.
Fetal anomalies v6.149 YY1AP1 Arina Puzriakova commented on gene: YY1AP1: 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.
Fetal anomalies v6.149 WNK3 Arina Puzriakova commented on gene: WNK3: The rating of this gene has been updated to Green and the mode of inheritance set to X-LINKED: hemizygous mutation in males, biallelic mutations in females following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 VPS51 Arina Puzriakova commented on gene: VPS51: 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.
Fetal anomalies v6.149 VPS50 Arina Puzriakova commented on gene: VPS50: 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.
Fetal anomalies v6.149 VPS33A Arina Puzriakova commented on gene: VPS33A: 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.
Fetal anomalies v6.149 UGGT1 Arina Puzriakova commented on gene: UGGT1: 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.
Fetal anomalies v6.149 TTC26 Arina Puzriakova commented on gene: TTC26: 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.
Fetal anomalies v6.149 TPRKB Arina Puzriakova commented on gene: TPRKB: 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.
Fetal anomalies v6.149 TP53RK Arina Puzriakova commented on gene: TP53RK: 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.
Fetal anomalies v6.149 TMEM251 Arina Puzriakova commented on gene: TMEM251: 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.
Fetal anomalies v6.149 TMEM17 Arina Puzriakova commented on gene: TMEM17: 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.
Fetal anomalies v6.149 TMEM167A Arina Puzriakova commented on gene: TMEM167A: 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.
Fetal anomalies v6.149 THUMPD1 Arina Puzriakova commented on gene: THUMPD1: 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.
Fetal anomalies v6.149 TASP1 Arina Puzriakova commented on gene: TASP1: 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.
Fetal anomalies v6.149 SOX4 Arina Puzriakova commented on gene: SOX4: 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.
Fetal anomalies v6.149 SMG8 Arina Puzriakova commented on gene: SMG8: 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.
Fetal anomalies v6.149 SMC5 Arina Puzriakova commented on gene: SMC5: 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.
Fetal anomalies v6.149 SMARCC2 Arina Puzriakova commented on gene: SMARCC2: 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.
Fetal anomalies v6.149 SLF2 Arina Puzriakova commented on gene: SLF2: 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.
Fetal anomalies v6.149 SLC5A6 Arina Puzriakova commented on gene: SLC5A6: 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.
Fetal anomalies v6.149 SKOR2 Arina Puzriakova commented on gene: SKOR2: 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.
Fetal anomalies v6.149 SIX2 Arina Puzriakova commented on gene: SIX2: 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.
Fetal anomalies v6.149 SCNM1 Arina Puzriakova commented on gene: SCNM1: 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.
Fetal anomalies v6.149 SATB1 Arina Puzriakova commented on gene: SATB1: 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.
Fetal anomalies v6.149 SART3 Arina Puzriakova commented on gene: SART3: 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.
Fetal anomalies v6.149 RSG1 Arina Puzriakova commented on gene: RSG1: 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.
Fetal anomalies v6.149 RNU7-1 Arina Puzriakova commented on gene: RNU7-1: 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.
Fetal anomalies v6.149 RHOBTB2 Arina Puzriakova commented on gene: RHOBTB2: The rating of this gene has been updated to Green and the mode of inheritance set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 RBBP5 Arina Puzriakova commented on gene: RBBP5: 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.
Fetal anomalies v6.149 RALGAPA1 Arina Puzriakova commented on gene: RALGAPA1: 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.
Fetal anomalies v6.149 RALA Arina Puzriakova commented on gene: RALA: 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.
Fetal anomalies v6.149 PRKCI Arina Puzriakova commented on gene: PRKCI: 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.
Fetal anomalies v6.149 PRDM13 Arina Puzriakova commented on gene: PRDM13: 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.
Fetal anomalies v6.149 PPP1R21 Arina Puzriakova commented on gene: PPP1R21: 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.
Fetal anomalies v6.149 PLXNA1 Arina Puzriakova commented on gene: PLXNA1: 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.
Fetal anomalies v6.149 PIGU Arina Puzriakova commented on gene: PIGU: 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.
Fetal anomalies v6.149 PIGK Arina Puzriakova commented on gene: PIGK: 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.
Fetal anomalies v6.149 PIGB Arina Puzriakova commented on gene: PIGB: 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.
Fetal anomalies v6.149 PDIA6 Arina Puzriakova commented on gene: PDIA6: 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.
Fetal anomalies v6.149 NUP133 Arina Puzriakova commented on gene: NUP133: 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.
Fetal anomalies v6.149 NR6A1 Arina Puzriakova commented on gene: NR6A1: 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.
Fetal anomalies v6.149 MYLPF Arina Puzriakova commented on gene: MYLPF: 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.
Fetal anomalies v6.149 LSM1 Arina Puzriakova commented on gene: LSM1: 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.
Fetal anomalies v6.149 LRRC32 Arina Puzriakova commented on gene: LRRC32: 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.
Fetal anomalies v6.149 LMOD2 Arina Puzriakova commented on gene: LMOD2: 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.
Fetal anomalies v6.149 LEF1 Arina Puzriakova commented on gene: LEF1: 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.
Fetal anomalies v6.149 KDM4B Arina Puzriakova commented on gene: KDM4B: 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.
Fetal anomalies v6.149 INPP4A Arina Puzriakova commented on gene: INPP4A: 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.
Fetal anomalies v6.149 IL6ST Arina Puzriakova commented on gene: IL6ST: 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.
Fetal anomalies v6.149 IFT57 Arina Puzriakova commented on gene: IFT57: 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.
Fetal anomalies v6.149 HNRNPR Arina Puzriakova commented on gene: HNRNPR: 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.
Fetal anomalies v6.149 HNRNPH1 Arina Puzriakova commented on gene: HNRNPH1: 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.
Fetal anomalies v6.149 HERC2 Arina Puzriakova commented on gene: HERC2: 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.
Fetal anomalies v6.149 H3F3B Arina Puzriakova commented on gene: H3F3B: 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.
Fetal anomalies v6.149 GTF3C3 Arina Puzriakova commented on gene: GTF3C3: 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.
Fetal anomalies v6.149 GON7 Arina Puzriakova commented on gene: GON7: 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.
Fetal anomalies v6.149 GINS3 Arina Puzriakova commented on gene: GINS3: 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.
Fetal anomalies v6.149 FGF4 Arina Puzriakova commented on gene: FGF4: 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.
Fetal anomalies v6.149 FEM1B Arina Puzriakova commented on gene: FEM1B: 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.
Fetal anomalies v6.149 FBXW7 Arina Puzriakova commented on gene: FBXW7: 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.
Fetal anomalies v6.149 FBXO28 Arina Puzriakova commented on gene: FBXO28: 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.
Fetal anomalies v6.149 EMC10 Arina Puzriakova commented on gene: EMC10: 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.
Fetal anomalies v6.149 EIF4A2 Arina Puzriakova commented on gene: EIF4A2: The rating of this gene has been updated to Green and the mode of inheritance set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 DPH5 Arina Puzriakova commented on gene: DPH5: 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.
Fetal anomalies v6.149 DOT1L Arina Puzriakova commented on gene: DOT1L: 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.
Fetal anomalies v6.149 DHX37 Arina Puzriakova commented on gene: DHX37: 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.
Fetal anomalies v6.149 CSDE1 Arina Puzriakova commented on gene: CSDE1: 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.
Fetal anomalies v6.149 CLCNKA Arina Puzriakova commented on gene: CLCNKA: 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.
Fetal anomalies v6.149 CLCN3 Arina Puzriakova commented on gene: CLCN3: The rating of this gene has been updated to Green and the mode of inheritance set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 CEP76 Arina Puzriakova commented on gene: CEP76: 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.
Fetal anomalies v6.149 CDC42BPB Arina Puzriakova commented on gene: CDC42BPB: 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.
Fetal anomalies v6.149 CDC42 Arina Puzriakova commented on gene: CDC42: 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.
Fetal anomalies v6.149 CCDC88A Arina Puzriakova commented on gene: CCDC88A: 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.
Fetal anomalies v6.149 CCDC32 Arina Puzriakova commented on gene: CCDC32: 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.
Fetal anomalies v6.149 CBFB Arina Puzriakova commented on gene: CBFB: 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.
Fetal anomalies v6.149 CAMSAP1 Arina Puzriakova commented on gene: CAMSAP1: 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.
Fetal anomalies v6.149 BRF2 Arina Puzriakova commented on gene: BRF2: 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.
Fetal anomalies v6.149 BBIP1 Arina Puzriakova commented on gene: BBIP1: 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.
Fetal anomalies v6.149 ARF3 Arina Puzriakova commented on gene: ARF3: 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.
Fetal anomalies v6.149 ADAT3 Arina Puzriakova commented on gene: ADAT3: 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.
Fetal anomalies v6.149 ABI2 Arina Puzriakova commented on gene: ABI2: 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.
Fetal anomalies v6.149 YRDC Arina Puzriakova commented on gene: YRDC: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 WSB2 Arina Puzriakova commented on gene: WSB2: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 WDR91 Arina Puzriakova commented on gene: WDR91: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 TUBGCP2 Arina Puzriakova commented on gene: TUBGCP2: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 TRIO Arina Puzriakova commented on gene: TRIO: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 SNAPIN Arina Puzriakova commented on gene: SNAPIN: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 SHROOM4 Arina Puzriakova commented on gene: SHROOM4: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 SELENON Arina Puzriakova commented on gene: SELENON: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 PTBP1 Arina Puzriakova commented on gene: PTBP1: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 PPP1R12A Arina Puzriakova commented on gene: PPP1R12A: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 PDCD2 Arina Puzriakova commented on gene: PDCD2: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 NSD2 Arina Puzriakova commented on gene: NSD2: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 NOVA2 Arina Puzriakova commented on gene: NOVA2: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 MNS1 Arina Puzriakova commented on gene: MNS1: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 MAST1 Arina Puzriakova commented on gene: MAST1: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 MAPK8IP3 Arina Puzriakova commented on gene: MAPK8IP3: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 KIAA0556 Arina Puzriakova commented on gene: KIAA0556: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 KCNJ8 Arina Puzriakova commented on gene: KCNJ8: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 HMGB1 Arina Puzriakova commented on gene: HMGB1: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 GPKOW Arina Puzriakova commented on gene: GPKOW: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 GATAD2B Arina Puzriakova commented on gene: GATAD2B: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 FOXI3 Arina Puzriakova commented on gene: FOXI3: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 EXOSC9 Arina Puzriakova commented on gene: EXOSC9: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 CLCNKB Arina Puzriakova commented on gene: CLCNKB: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 CACHD1 Arina Puzriakova commented on gene: CACHD1: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 BRF1 Arina Puzriakova commented on gene: BRF1: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 B9D1 Arina Puzriakova commented on gene: B9D1: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 ASXL2 Arina Puzriakova commented on gene: ASXL2: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 ANKLE2 Arina Puzriakova commented on gene: ANKLE2: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.149 ACVR1 Arina Puzriakova commented on gene: ACVR1: The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.
Fetal anomalies v6.148 ZPR1 Arina Puzriakova commented on gene: ZPR1
Fetal anomalies v6.148 ZNF668 Arina Puzriakova commented on gene: ZNF668
Fetal anomalies v6.148 ZDHHC9 Arina Puzriakova commented on gene: ZDHHC9
Fetal anomalies v6.148 ZBTB7A Arina Puzriakova commented on gene: ZBTB7A
Fetal anomalies v6.148 YY1AP1 Arina Puzriakova commented on gene: YY1AP1
Fetal anomalies v6.148 YWHAE Arina Puzriakova commented on gene: YWHAE
Fetal anomalies v6.148 YRDC Arina Puzriakova commented on gene: YRDC
Fetal anomalies v6.148 WSB2 Arina Puzriakova commented on gene: WSB2
Fetal anomalies v6.148 WNK3 Arina Puzriakova commented on gene: WNK3
Fetal anomalies v6.148 WDR91 Arina Puzriakova commented on gene: WDR91: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 WDR11 Arina Puzriakova commented on gene: WDR11
Fetal anomalies v6.148 WASHC3 Arina Puzriakova commented on gene: WASHC3
Fetal anomalies v6.148 VPS51 Arina Puzriakova commented on gene: VPS51
Fetal anomalies v6.148 VPS50 Arina Puzriakova commented on gene: VPS50
Fetal anomalies v6.148 VPS33A Arina Puzriakova commented on gene: VPS33A
Fetal anomalies v6.148 UGGT1 Arina Puzriakova commented on gene: UGGT1
Fetal anomalies v6.148 TUBGCP2 Arina Puzriakova commented on gene: TUBGCP2
Fetal anomalies v6.148 TTC26 Arina Puzriakova commented on gene: TTC26
Fetal anomalies v6.148 TRPM4 Arina Puzriakova commented on gene: TRPM4
Fetal anomalies v6.148 TRIO Arina Puzriakova commented on gene: TRIO
Fetal anomalies v6.148 TPRKB Arina Puzriakova commented on gene: TPRKB
Fetal anomalies v6.148 TP53RK Arina Puzriakova commented on gene: TP53RK
Fetal anomalies v6.148 TMPRSS7 Arina Puzriakova commented on gene: TMPRSS7
Fetal anomalies v6.148 TMEM263 Arina Puzriakova commented on gene: TMEM263
Fetal anomalies v6.148 TMEM251 Arina Puzriakova commented on gene: TMEM251
Fetal anomalies v6.148 TMEM17 Arina Puzriakova commented on gene: TMEM17
Fetal anomalies v6.148 TMEM167A Arina Puzriakova commented on gene: TMEM167A
Fetal anomalies v6.148 THUMPD1 Arina Puzriakova commented on gene: THUMPD1
Fetal anomalies v6.148 TH Arina Puzriakova commented on gene: TH
Fetal anomalies v6.148 TEK Arina Puzriakova commented on gene: TEK
Fetal anomalies v6.148 TASP1 Arina Puzriakova commented on gene: TASP1
Fetal anomalies v6.148 TAF13 Arina Puzriakova commented on gene: TAF13
Fetal anomalies v6.148 SPTBN1 Arina Puzriakova commented on gene: SPTBN1
Fetal anomalies v6.148 SPOP Arina Puzriakova commented on gene: SPOP
Fetal anomalies v6.148 SOX4 Arina Puzriakova commented on gene: SOX4
Fetal anomalies v6.148 SNAPIN Arina Puzriakova commented on gene: SNAPIN: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 SMG8 Arina Puzriakova commented on gene: SMG8
Fetal anomalies v6.148 SMC5 Arina Puzriakova commented on gene: SMC5
Fetal anomalies v6.148 SMARCC2 Arina Puzriakova commented on gene: SMARCC2
Fetal anomalies v6.148 SMAD5 Arina Puzriakova commented on gene: SMAD5
Fetal anomalies v6.148 SLF2 Arina Puzriakova commented on gene: SLF2
Fetal anomalies v6.148 SLC9A6 Arina Puzriakova commented on gene: SLC9A6
Fetal anomalies v6.148 SLC5A6 Arina Puzriakova commented on gene: SLC5A6
Fetal anomalies v6.148 SLC13A1 Arina Puzriakova commented on gene: SLC13A1
Fetal anomalies v6.148 SKOR2 Arina Puzriakova commented on gene: SKOR2
Fetal anomalies v6.148 SIX2 Arina Puzriakova commented on gene: SIX2
Fetal anomalies v6.148 SIX1 Arina Puzriakova commented on gene: SIX1
Fetal anomalies v6.148 SHROOM4 Arina Puzriakova commented on gene: SHROOM4: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 SGCG Arina Puzriakova commented on gene: SGCG: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 SGCD Arina Puzriakova commented on gene: SGCD
Fetal anomalies v6.148 SGCB Arina Puzriakova commented on gene: SGCB
Fetal anomalies v6.148 SGCA Arina Puzriakova commented on gene: SGCA
Fetal anomalies v6.148 SF1 Arina Puzriakova commented on gene: SF1
Fetal anomalies v6.148 SEPHS1 Arina Puzriakova commented on gene: SEPHS1
Fetal anomalies v6.148 SELENON Arina Puzriakova commented on gene: SELENON
Fetal anomalies v6.148 SCNM1 Arina Puzriakova commented on gene: SCNM1
Fetal anomalies v6.148 SATB1 Arina Puzriakova commented on gene: SATB1
Fetal anomalies v6.148 SART3 Arina Puzriakova commented on gene: SART3
Fetal anomalies v6.148 RSG1 Arina Puzriakova commented on gene: RSG1
Fetal anomalies v6.148 RREB1 Arina Puzriakova commented on gene: RREB1
Fetal anomalies v6.148 ROBO4 Arina Puzriakova commented on gene: ROBO4
Fetal anomalies v6.148 RNU7-1 Arina Puzriakova commented on gene: RNU7-1
Fetal anomalies v6.148 RNU5A-1 Arina Puzriakova commented on gene: RNU5A-1: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 RNU2-2P Arina Puzriakova commented on gene: RNU2-2P
Fetal anomalies v6.148 RNPC3 Arina Puzriakova commented on gene: RNPC3
Fetal anomalies v6.148 RNF13 Arina Puzriakova commented on gene: RNF13
Fetal anomalies v6.148 RHOBTB2 Arina Puzriakova commented on gene: RHOBTB2
Fetal anomalies v6.148 RBBP5 Arina Puzriakova commented on gene: RBBP5
Fetal anomalies v6.148 RASA2 Arina Puzriakova commented on gene: RASA2
Fetal anomalies v6.148 RALGAPA1 Arina Puzriakova commented on gene: RALGAPA1
Fetal anomalies v6.148 RALA Arina Puzriakova commented on gene: RALA
Fetal anomalies v6.148 RAD51C Arina Puzriakova commented on gene: RAD51C
Fetal anomalies v6.148 RAB35 Arina Puzriakova commented on gene: RAB35
Fetal anomalies v6.148 PURA Arina Puzriakova commented on gene: PURA: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 PTBP1 Arina Puzriakova commented on gene: PTBP1: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 PRKCI Arina Puzriakova commented on gene: PRKCI
Fetal anomalies v6.148 PRDM13 Arina Puzriakova commented on gene: PRDM13: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 PPP1R21 Arina Puzriakova commented on gene: PPP1R21
Fetal anomalies v6.148 PPP1R13L Arina Puzriakova commented on gene: PPP1R13L
Fetal anomalies v6.148 PPP1R12A Arina Puzriakova commented on gene: PPP1R12A: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 POLA1 Arina Puzriakova commented on gene: POLA1
Fetal anomalies v6.148 PMS2 Arina Puzriakova commented on gene: PMS2
Fetal anomalies v6.148 PLXNB3 Arina Puzriakova commented on gene: PLXNB3: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 PLXNB2 Arina Puzriakova commented on gene: PLXNB2
Fetal anomalies v6.148 PLXNA1 Arina Puzriakova commented on gene: PLXNA1
Fetal anomalies v6.148 PLOD3 Arina Puzriakova commented on gene: PLOD3: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 PIGU Arina Puzriakova commented on gene: PIGU
Fetal anomalies v6.148 PIGK Arina Puzriakova commented on gene: PIGK
Fetal anomalies v6.148 PIGB Arina Puzriakova commented on gene: PIGB
Fetal anomalies v6.148 PDIA6 Arina Puzriakova commented on gene: PDIA6
Fetal anomalies v6.148 PDCD6IP Arina Puzriakova commented on gene: PDCD6IP
Fetal anomalies v6.148 PDCD2 Arina Puzriakova commented on gene: PDCD2: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 PCLO Arina Puzriakova commented on gene: PCLO: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 PATJ Arina Puzriakova commented on gene: PATJ: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 PACSIN3 Arina Puzriakova commented on gene: PACSIN3
Fetal anomalies v6.148 NUP133 Arina Puzriakova commented on gene: NUP133
Fetal anomalies v6.148 NUDCD2 Arina Puzriakova commented on gene: NUDCD2
Fetal anomalies v6.148 NSD2 Arina Puzriakova commented on gene: NSD2: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 NR6A1 Arina Puzriakova commented on gene: NR6A1
Fetal anomalies v6.148 NOVA2 Arina Puzriakova commented on gene: NOVA2
Fetal anomalies v6.148 NOTCH3 Arina Puzriakova commented on gene: NOTCH3
Fetal anomalies v6.148 MYLPF Arina Puzriakova commented on gene: MYLPF
Fetal anomalies v6.148 MSH6 Arina Puzriakova commented on gene: MSH6
Fetal anomalies v6.148 MSH2 Arina Puzriakova commented on gene: MSH2
Fetal anomalies v6.148 MNS1 Arina Puzriakova commented on gene: MNS1: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 MMP9 Arina Puzriakova commented on gene: MMP9
Fetal anomalies v6.148 MLH1 Arina Puzriakova commented on gene: MLH1
Fetal anomalies v6.148 MAST1 Arina Puzriakova commented on gene: MAST1
Fetal anomalies v6.148 MAPK8IP3 Arina Puzriakova commented on gene: MAPK8IP3
Fetal anomalies v6.148 LSM1 Arina Puzriakova commented on gene: LSM1
Fetal anomalies v6.148 LRRC32 Arina Puzriakova commented on gene: LRRC32
Fetal anomalies v6.148 LMOD2 Arina Puzriakova commented on gene: LMOD2
Fetal anomalies v6.148 LINC01578 Arina Puzriakova commented on gene: LINC01578: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 LHX2 Arina Puzriakova commented on gene: LHX2
Fetal anomalies v6.148 LEF1 Arina Puzriakova commented on gene: LEF1
Fetal anomalies v6.148 LDB3 Arina Puzriakova commented on gene: LDB3
Fetal anomalies v6.148 KIAA0556 Arina Puzriakova commented on gene: KIAA0556: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 KDM4B Arina Puzriakova commented on gene: KDM4B
Fetal anomalies v6.148 KCNQ5 Arina Puzriakova commented on gene: KCNQ5
Fetal anomalies v6.148 KCNN4 Arina Puzriakova commented on gene: KCNN4
Fetal anomalies v6.148 KCNJ8 Arina Puzriakova commented on gene: KCNJ8
Fetal anomalies v6.148 INPP4A Arina Puzriakova commented on gene: INPP4A
Fetal anomalies v6.148 IL6ST Arina Puzriakova commented on gene: IL6ST
Fetal anomalies v6.148 IKZF2 Arina Puzriakova commented on gene: IKZF2
Fetal anomalies v6.148 IFT57 Arina Puzriakova commented on gene: IFT57
Fetal anomalies v6.148 HNRNPR Arina Puzriakova commented on gene: HNRNPR
Fetal anomalies v6.148 HNRNPH1 Arina Puzriakova commented on gene: HNRNPH1
Fetal anomalies v6.148 HMGB1 Arina Puzriakova commented on gene: HMGB1
Fetal anomalies v6.148 HEY2 Arina Puzriakova commented on gene: HEY2
Fetal anomalies v6.148 HERC2 Arina Puzriakova commented on gene: HERC2
Fetal anomalies v6.148 HDAC2 Arina Puzriakova commented on gene: HDAC2
Fetal anomalies v6.148 HACD1 Arina Puzriakova commented on gene: HACD1
Fetal anomalies v6.148 H3F3B Arina Puzriakova commented on gene: H3F3B
Fetal anomalies v6.148 GTF3C3 Arina Puzriakova commented on gene: GTF3C3
Fetal anomalies v6.148 GPKOW Arina Puzriakova commented on gene: GPKOW
Fetal anomalies v6.148 GON7 Arina Puzriakova commented on gene: GON7
Fetal anomalies v6.148 GNPNAT1 Arina Puzriakova commented on gene: GNPNAT1: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 GINS3 Arina Puzriakova commented on gene: GINS3
Fetal anomalies v6.148 GATAD2B Arina Puzriakova commented on gene: GATAD2B
Fetal anomalies v6.148 FOXI3 Arina Puzriakova commented on gene: FOXI3
Fetal anomalies v6.148 FIBP Arina Puzriakova commented on gene: FIBP
Fetal anomalies v6.148 FGF4 Arina Puzriakova commented on gene: FGF4
Fetal anomalies v6.148 FEM1B Arina Puzriakova commented on gene: FEM1B
Fetal anomalies v6.148 FBXW7 Arina Puzriakova commented on gene: FBXW7
Fetal anomalies v6.148 FBXO28 Arina Puzriakova commented on gene: FBXO28
Fetal anomalies v6.148 FBXO11 Arina Puzriakova commented on gene: FBXO11: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 EXOSC9 Arina Puzriakova commented on gene: EXOSC9: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 EXOSC1 Arina Puzriakova commented on gene: EXOSC1: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 ETV2 Arina Puzriakova commented on gene: ETV2
Fetal anomalies v6.148 ENPP5 Arina Puzriakova commented on gene: ENPP5
Fetal anomalies v6.148 EMC10 Arina Puzriakova commented on gene: EMC10
Fetal anomalies v6.148 ELFN1 Arina Puzriakova commented on gene: ELFN1
Fetal anomalies v6.148 EIF4A2 Arina Puzriakova commented on gene: EIF4A2
Fetal anomalies v6.148 EDN1 Arina Puzriakova commented on gene: EDN1
Fetal anomalies v6.148 EDA Arina Puzriakova commented on gene: EDA: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 DPH5 Arina Puzriakova commented on gene: DPH5
Fetal anomalies v6.148 DOT1L Arina Puzriakova commented on gene: DOT1L
Fetal anomalies v6.148 DNAH14 Arina Puzriakova commented on gene: DNAH14
Fetal anomalies v6.148 DLG3 Arina Puzriakova commented on gene: DLG3
Fetal anomalies v6.148 DIP2C Arina Puzriakova commented on gene: DIP2C
Fetal anomalies v6.148 DHX37 Arina Puzriakova commented on gene: DHX37: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 DHRS3 Arina Puzriakova commented on gene: DHRS3
Fetal anomalies v6.148 DHPS Arina Puzriakova commented on gene: DHPS
Fetal anomalies v6.148 DDX23 Arina Puzriakova commented on gene: DDX23
Fetal anomalies v6.148 DDR1 Arina Puzriakova commented on gene: DDR1
Fetal anomalies v6.148 CSDE1 Arina Puzriakova commented on gene: CSDE1
Fetal anomalies v6.148 CRELD1 Arina Puzriakova commented on gene: CRELD1
Fetal anomalies v6.148 CPOX Arina Puzriakova commented on gene: CPOX
Fetal anomalies v6.148 CLCNKB Arina Puzriakova commented on gene: CLCNKB
Fetal anomalies v6.148 CLCNKA Arina Puzriakova commented on gene: CLCNKA
Fetal anomalies v6.148 CLCN3 Arina Puzriakova commented on gene: CLCN3
Fetal anomalies v6.148 CHD8 Arina Puzriakova commented on gene: CHD8
Fetal anomalies v6.148 CEP76 Arina Puzriakova commented on gene: CEP76
Fetal anomalies v6.148 CEP162 Arina Puzriakova commented on gene: CEP162
Fetal anomalies v6.148 CDX1 Arina Puzriakova commented on gene: CDX1
Fetal anomalies v6.148 CDH11 Arina Puzriakova commented on gene: CDH11: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 CDC42BPB Arina Puzriakova commented on gene: CDC42BPB
Fetal anomalies v6.148 CDC42 Arina Puzriakova commented on gene: CDC42
Fetal anomalies v6.148 CDC40 Arina Puzriakova commented on gene: CDC40: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 CCT8 Arina Puzriakova commented on gene: CCT8: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 CCP110 Arina Puzriakova commented on gene: CCP110: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 CCM2L Arina Puzriakova commented on gene: CCM2L
Fetal anomalies v6.148 CCDC88A Arina Puzriakova commented on gene: CCDC88A
Fetal anomalies v6.148 CCDC32 Arina Puzriakova commented on gene: CCDC32
Fetal anomalies v6.148 CBFB Arina Puzriakova commented on gene: CBFB
Fetal anomalies v6.148 CAMSAP1 Arina Puzriakova commented on gene: CAMSAP1
Fetal anomalies v6.148 CACHD1 Arina Puzriakova commented on gene: CACHD1
Fetal anomalies v6.148 BUB1 Arina Puzriakova commented on gene: BUB1
Fetal anomalies v6.148 BRWD3 Arina Puzriakova commented on gene: BRWD3
Fetal anomalies v6.148 BRF2 Arina Puzriakova commented on gene: BRF2
Fetal anomalies v6.148 BRF1 Arina Puzriakova commented on gene: BRF1
Fetal anomalies v6.148 BNIP1 Arina Puzriakova commented on gene: BNIP1
Fetal anomalies v6.148 BBIP1 Arina Puzriakova commented on gene: BBIP1
Fetal anomalies v6.148 BAZ2B Arina Puzriakova commented on gene: BAZ2B
Fetal anomalies v6.148 B9D1 Arina Puzriakova commented on gene: B9D1: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 ATP6V0A1 Arina Puzriakova commented on gene: ATP6V0A1
Fetal anomalies v6.148 ASXL2 Arina Puzriakova commented on gene: ASXL2
Fetal anomalies v6.148 ARHGEF40 Arina Puzriakova commented on gene: ARHGEF40
Fetal anomalies v6.148 ARHGEF17 Arina Puzriakova commented on gene: ARHGEF17: This gene and phenotype were reviewed during meetings between November 2025 & January 2026. 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, Elizabeth Young and Sarah Graham (Central & South GLH), Natalie Chandler and Elizabeth Scotchman (North Thames GLH), and Tazeen Ashraf, Anna De Burca, Natalie Canham, Samantha Doyle, Alice Gardham, Victoria Harrison, Tessa Homfray, Esther Kinning, and Soo-Mi Park (R21 Clinical Oversight Group).
Fetal anomalies v6.148 ARF3 Arina Puzriakova commented on gene: ARF3
Fetal anomalies v6.148 ARAF Arina Puzriakova commented on gene: ARAF
Fetal anomalies v6.148 ANKRD17 Arina Puzriakova commented on gene: ANKRD17
Fetal anomalies v6.148 ANKLE2 Arina Puzriakova commented on gene: ANKLE2
Fetal anomalies v6.148 AMOT Arina Puzriakova commented on gene: AMOT